Sample records for experimental autoimmune uveitis

  1. Targeting CD6 for the treatment of experimental autoimmune uveitis.

    PubMed

    Zhang, Lingjun; Li, Yan; Qiu, Wen; Bell, Brent A; Dvorina, Nina; Baldwin, William M; Singer, Nora; Kern, Timothy; Caspi, Rachel R; Fox, David A; Lin, Feng

    2018-06-01

    CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively transferred into WT naïve mice to confirm the impact of CD6 on T cells. In addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies exhibiting cross-reactivity with human CD6 were screened and identified for treatment studies. In CD6 KO mice with EAU, we found significantly decreased retinal inflammation and reduced autoreactive T-cell responses, and confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment. Notably, one of these cross-reactive mAbs significantly ameliorated retinal inflammation in EAU induced by the adoptive transfer of uveitogenic T cells. Together, these data strongly suggest that CD6 plays a previously unknown, but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this blinding disease. In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be valuable tools for testing CD6-targeted therapies in other mouse models of human diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Intravitreal injection of anti-Interleukin (IL)-6 antibody attenuates experimental autoimmune uveitis in mice.

    PubMed

    Tode, Jan; Richert, Elisabeth; Koinzer, Stefan; Klettner, Alexa; Pickhinke, Ute; Garbers, Christoph; Rose-John, Stefan; Nölle, Bernhard; Roider, Johann

    2017-08-01

    To evaluate the effect of an intravitreally applied anti-IL-6 antibody for the treatment of experimental autoimmune uveitis (EAU). EAU was induced in female B10.RIII mice by Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, boosted by Pertussis toxin. Single blinded intravitreal injections of anti-IL-6 antibody were applied 5-7days as well as 8-10days (3day interval) after EAU induction into the randomized treatment eye and phosphate buffered saline (PBS) into the fellow control eye. Clinical and fluorescein angiography scoring (6 EAU grades) was done at each injection day and at enucleation day 14. Enucleated eyes were either scored histologically (6 EAU grades) or examined by ELISA for levels of IL-6, IL-17 and IL-6 soluble Receptor (sIL-6R). Uveitis developed in all 12 mice. Clinical uveitis score was significantly reduced (p=0.035) in treated eyes (median 2.0, range 0-4.0, n=12) compared to the fellow control eyes (median 3.0, range 1.0-4.0, n=12). Angiography scores were reduced in 9/12 treated eyes and histological scores in 3/4 treated eyes compared to the fellow control eyes. Cytokine levels were determined in 8 mice, of which 4 responded to anti-IL-6 treatment and 4 did not respond. All mice responding to treatment had a significant reduction of IL-6 (p<0.01) and IL-17 (p=0.01) levels in treated eyes compared to the fellow control eyes. This difference was not seen in non-responding mice. Intravitreal anti-IL-6 treatment significantly attenuates experimental autoimmune uveitis in mice. EAU activity correlates with ocular IL-6 and IL-17 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nakamura, Yukiko K.; Metea, Christina; Karstens, Lisa

    The bacteria that live normally in our intestinal tract, or the gut microbiota contribute to the pathogenesis of extra intestinal autoimmune disease via their ability to dynamically educate the immune system. For example, in a mouse model of relapsing, remitting multiple sclerosis (MS), experimental autoimmune encephalomyelitis or EAE, several studies demonstrated that commensal microorganisms are essential in causing clinical disease activity. Interestingly, MS patients have a distinct gut microbiota to healthy controls. Several studies have also illustrated the importance of the gut microbiome in the development of other diseases, including Type 1 diabetes, metabolic syndrome, rheumatoid arthritis, and ankylosing spondylitis.more » Furthermore, HLA=B27 transgenic rats, which develop spontaneous spondyloarthropathy analogous to patients who have ankylosing spondylitis, associated with uveitis in humans, do not develop intestinal or peripheral join inflammation when raised in a germ-free environment. Our group has shown that HLA-B27 transgenic rats have an altered intestinal microbiota compared to healthy control rats. Given the similarities between the central nervous system (CNS) and the retina, as well as co-expression of potentially immunogenic self-antigens from the CNS and joint in the eye, we hypothesized that modulating the gut microbiome can result in amelioration of autoimmune uveitis. Although uveitis is a heterogeneous collection of diseases, in general immune-mediated, non-infectious, uveitis is thought to be due to a combination of genetic and environmental factors. It arises from an imbalance between the regulatory and effector arms of the immune system, result in an inappropriate immune reaction at an otherwise immune-privileged tissue site, the eye. Th1 and Th17 T lymphocytes are examples of effector immune cell subsets that my contribute to inflammatory disease of the eye, whereas regulatory T cells (Tregs) are an example of a regulatory immune

  4. Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis

    DOE PAGES

    Nakamura, Yukiko K.; Metea, Christina; Karstens, Lisa; ...

    2016-07-01

    The bacteria that live normally in our intestinal tract, or the gut microbiota contribute to the pathogenesis of extra intestinal autoimmune disease via their ability to dynamically educate the immune system. For example, in a mouse model of relapsing, remitting multiple sclerosis (MS), experimental autoimmune encephalomyelitis or EAE, several studies demonstrated that commensal microorganisms are essential in causing clinical disease activity. Interestingly, MS patients have a distinct gut microbiota to healthy controls. Several studies have also illustrated the importance of the gut microbiome in the development of other diseases, including Type 1 diabetes, metabolic syndrome, rheumatoid arthritis, and ankylosing spondylitis.more » Furthermore, HLA=B27 transgenic rats, which develop spontaneous spondyloarthropathy analogous to patients who have ankylosing spondylitis, associated with uveitis in humans, do not develop intestinal or peripheral join inflammation when raised in a germ-free environment. Our group has shown that HLA-B27 transgenic rats have an altered intestinal microbiota compared to healthy control rats. Given the similarities between the central nervous system (CNS) and the retina, as well as co-expression of potentially immunogenic self-antigens from the CNS and joint in the eye, we hypothesized that modulating the gut microbiome can result in amelioration of autoimmune uveitis. Although uveitis is a heterogeneous collection of diseases, in general immune-mediated, non-infectious, uveitis is thought to be due to a combination of genetic and environmental factors. It arises from an imbalance between the regulatory and effector arms of the immune system, result in an inappropriate immune reaction at an otherwise immune-privileged tissue site, the eye. Th1 and Th17 T lymphocytes are examples of effector immune cell subsets that my contribute to inflammatory disease of the eye, whereas regulatory T cells (Tregs) are an example of a regulatory immune

  5. CRALBP is a highly prevalent autoantigen for human autoimmune uveitis.

    PubMed

    Deeg, Cornelia A; Raith, Albert J; Amann, Barbara; Crabb, John W; Thurau, Stephan R; Hauck, Stefanie M; Ueffing, Marius; Wildner, Gerhild; Stangassinger, Manfred

    2007-01-01

    Cellular retinaldehyde binding protein (CRALBP) is an autoantigen in spontaneous equine recurrent uveitis. In order to test whether CRALBP contributes to human autoimmune uveitis, the specificity of antibodies from human uveitis patient's sera was first evaluated in two-dimensional (2D) Western blot analysis. Subsequent identification of the immunoreactive proteins by mass spectrometry resulted in the identification of CRALBP as a putative autoantigen. Additionally, sera from human uveitis and control patients were by Western blot using purified human recombinant CRALBP. Anti-CRALBP autoantibodies occur more frequently (P<.01) in human uveitis patients than in normal controls. Thirty out of 56 tested uveitis patient's sera contained autoantibodies reactive against CRALBP, compared to only four out of 23 normal control subjects. The presence of CRALBP autoantibodies in 54% of tested uveitis patients supports CRALBP as a possible autoantigen in human autoimmune uveitis.

  6. Uveitis in patients with autoimmune hepatitis.

    PubMed

    Lim, Lyndell L; Scarborough, John D; Thorne, Jennifer E; Graham, Elizabeth; Kempen, John H; Mackensen, Friederike; Nguyen, Quan Dong; Prabriputaloong, Tisha; Read, Russell W; Suhler, Eric B; Schwartz, Jonathan M; Smith, Justine R

    2009-02-01

    To report seven cases of uveitis occurring in patients with autoimmune hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic feature of AIH. Multicenter, retrospective, observational case series of patients with AIH and uveitis. One index case was identified at Oregon Health & Science University. Further cases were identified by a web-based survey of members of the American Uveitis Society, the International Uveitis Study Group, the Proctor Foundation mailing list server, and the First SUN International Workshop. Respondents were asked to provide clinical information about uveitis phenotype, AIH features, and treatment. Clinical information was obtained for seven individuals (four females and three males; age range, seven to 67 years) who suffered from AIH and uveitis. Average duration of follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location. Every patient had complications arising from his or her uveitis, including cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To treat the uveitis and/or AIH, the majority of patients required oral prednisone and all seven patients were treated with systemic immunosuppression. Despite the small size of this study, our findings suggest an association between AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight-threatening complications, necessitating systemic immunosuppression in some individuals.

  7. Role of DAF in protecting against T-cell autoreactivity that leads to experimental autoimmune uveitis.

    PubMed

    An, Fengqi; Li, Qing; Tu, Zhidan; Bu, Hong; Chan, Chi-Chao; Caspi, Rachel R; Lin, Feng

    2009-08-01

    To investigate the role of decay-accelerating factor (DAF), a cell surface complement regulator that recently has been linked to T-cell responses and autoimmunity in the pathogenesis of experimental autoimmune uveitis (EAU). EAU was induced in wild-type (WT) and Daf1(-/-) mice, and their disease severities, IRBP specific Th1/Th17 responses, and cytokine expression profiles were compared. In a test of the efficacy of treatment with soluble mouse DAF protein, EAU was induced in disease-susceptible B10.RIII mice, and they were treated with 0.5 mg soluble DAF protein or equal volume of PBS IP every other day. Retinal histology and IRBP-specific T-cell responses were compared after 14 days. Both EAU incidence and histopathology scores were significantly greater in Daf1(-/-) mice. There was a >10-fold greater mononuclear cell influx into the retina together with severe vasculitic lesions, retinal folding, and photoreceptor cell layer destruction. There were 5- to 7-fold greater Th1 and 3- to 4-fold greater Th17 responses against IRBP in Daf1(-/-) mice with EAU, and they expressed significantly elevated levels of GM-CSF, IL-2, IL-3, and IFN-gamma. WT B10.RIII mice that received soluble DAF protein treatments exhibited decreased IRBP-specific Th1/Th17 responses and were protected from retinal injury compared with the mice that received PBS treatments. DAF significantly influences IRBP-specific Th1 and Th17 responses and disease severity in EAU. Systemic upregulation of DAF levels could be used to suppress retinal antigen(s)-specific autoimmunity to treat autoimmune posterior uveitis.

  8. Immunological and pathological investigations in equine experimental uveitis.

    PubMed

    Simeonova, Galina P; Krastev, Svetozar Z; Simeonov, Radostin S

    2016-12-01

    The pathogenic mechanism of equine recurrent uveitis (ERU) is still poorly defined and many variations between experimental animal models and spontaneous disease exist. The aim of our study was to investigate if Th17 cell-mediated response plays role in the pathogenesis of the used experimental model in horses and to reveal its pathological findings. Experimental uveitis was induced in 6 healthy horses. The concentrations of retinal autoantigen CRALBP and IL-17 were measured using ELISA in aqueous humor and vitreous body of the 12 inflamed eyes as well as in 12 control non-inflamed eyes taken from 6 horses in slaughter house. After centrifugation of the two eye media, smears were prepared and cytological investigation was performed. Tissue specimens were taken from all eye globes and were submitted to histopathological investigation. CRALBP and IL-17 concentrations were significantly elevated in eye media of horses with experimental uveitis in comparison with controls. Cytological and histopathological findings corresponded to the changes characteristic of chronic immune-mediated inflammation with mononuclear cell infiltration of uvea, choroid, retina, and eye media as well as severe retinal destruction. Our study demonstrated the involvement of the retinal autoantigen CRALBP as well as IL-17 in the pathogenesis of experimental uveitis in horses. These findings suggests that this experimental uveitis in horses may serve as a suitable animal model for investigation of IL-17- mediated immune response during spontaneous autoimmune uveitis in horses as well as in humans.

  9. Changes in matrix metalloproteinase network in a spontaneous autoimmune uveitis model.

    PubMed

    Hofmaier, Florian; Hauck, Stefanie M; Amann, Barbara; Degroote, Roxane L; Deeg, Cornelia A

    2011-04-08

    Autoimmune uveitis is a sight-threatening disease in which autoreactive T cells cross the blood-retinal barrier. Molecular mechanisms contributing to the loss of eye immune privilege in this autoimmune disease are not well understood. In this study, the authors investigated the changes in the matrix metalloproteinase network in spontaneous uveitis. Matrix metalloproteinase (MMP) MMP2, MMP9, and MMP14 expression and tissue inhibitor of metalloproteinase (TIMP)-2 and lipocalin 2 (LCN2) expression were analyzed using Western blot quantification. Enzyme activities were examined with zymography. Expression patterns of network candidates were revealed with immunohistochemistry, comparing physiological appearance and changes in a spontaneous recurrent uveitis model. TIMP2 protein expression was found to be decreased in both the vitreous and the retina of a spontaneous model for autoimmune uveitis (equine recurrent uveitis [ERU]), and TIMP2 activity was significantly reduced in ERU vitreous. Functionally associated MMPs such as MMP2, MMP14, and MMP9 were found to show altered or shifted expression and activity. Although MMP2 decreased in ERU vitreous, MMP9 expression and activity were found to be increased. These changes were reflected by profound changes within uveitic target tissue, where TIMP2, MMP9, and MMP14 decreased in expression, whereas MMP2 displayed a shifted expression pattern. LCN2, a potential stabilizer of MMP9, was found prominently expressed in equine healthy retina and displayed notable changes in expression patterns accompanied by significant upregulation in autoimmune conditions. Invading cells expressed MMP9 and LCN2. This study implicates a dysregulation or a change in functional protein-protein interactions in this TIMP2-associated protein network, together with altered expression of functionally related MMPs.

  10. Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line.

    PubMed

    Jia, Xiuzhi; Li, Jingbo; Shi, Dejing; Zhao, Yu; Dong, Yucui; Ju, Huanyu; Yang, Jinfeng; Sun, Jianhua; Li, Xia; Ren, Huan

    2014-01-01

    Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652) between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

  11. Dietary Omega-3 Fatty Acids Suppress Experimental Autoimmune Uveitis in Association with Inhibition of Th1 and Th17 Cell Function

    PubMed Central

    Shoda, Hiromi; Yanai, Ryoji; Yoshimura, Takeru; Nagai, Tomohiko; Kimura, Kazuhiro; Sobrin, Lucia; Connor, Kip M.; Sakoda, Yukimi; Tamada, Koji; Ikeda, Tsunehiko; Sonoda, Koh-Hei

    2015-01-01

    Omega (ω)–3 long-chain polyunsaturated fatty acids (LCPUFAs) inhibit the production of inflammatory mediators and thereby contribute to the regulation of inflammation. Experimental autoimmune uveitis (EAU) is a well-established animal model of autoimmune retinal inflammation. To investigate the potential effects of dietary intake of ω-3 LCPUFAs on uveitis, we examined the anti-inflammatory properties of these molecules in comparison with ω-6 LCPUFAs in a mouse EAU model. C57BL/6 mice were fed a diet containing ω-3 LCPUFAs or ω-6 LCPUFAs for 2 weeks before as well as after the induction of EAU by subcutaneous injection of a fragment of human interphotoreceptor retinoid-binding protein emulsified with complete Freund’s adjuvant. Both clinical and histological scores for uveitis were smaller for mice fed ω-3 LCPUFAs than for those fed ω-6 LCPUFAs. The concentrations of the T helper 1 (Th1) cytokine interferon-γ and the Th17 cytokine interleukin-17 in intraocular fluid as well as the production of these cytokines by lymph node cells were reduced for mice fed ω-3 LCPUFAs. Furthermore, the amounts of mRNAs for the Th1- and Th17-related transcription factors T-bet and RORγt, respectively, were reduced both in the retina and in lymph node cells of mice fed ω-3 LCPUFAs. Our results thus show that a diet enriched in ω-3 LCPUFAs suppressed uveitis in mice in association with inhibition of Th1 and Th17 cell function. PMID:26393358

  12. Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ‡

    PubMed Central

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

    2016-01-01

    Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1–20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8–14 days post-immunization, shortly before EAU expression, but ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses and this effect was γδ T cell-dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help improve the design of ADA- and AR-targeted therapies. PMID:26856700

  13. Local S100A8 Levels Correlate With Recurrence of Experimental Autoimmune Uveitis and Promote Pathogenic T Cell Activity

    PubMed Central

    Yun, Juan; Xiao, Tong; Zhou, Lei; Beuerman, Roger W.; Li, Juanjuan; Zhao, Yuan; Hadayer, Amir; Zhang, Xiaomin; Sun, Deming; Kaplan, Henry J.

    2018-01-01

    Purpose To investigate the role of damage-associated molecular patterns (DAMPs) in recurrent experimental autoimmune uveitis (EAU). Methods Recurrent EAU was induced in Lewis rats by interphotoreceptor retinoid-binding protein (IRBP) R16-peptide specific T cells (tEAU). Aqueous humor and serum samples were kinetically collected and DAMPs examined by quantitative proteomics, Western blot analysis, and ELISA. tEAU rats were treated with S100 inhibitor paquinimod followed by disease evaluation. The functions of T effector cells and T regulatory cells (Tregs) were compared between treated and nontreated groups. The expression of costimulatory molecules on antigen-presenting cells was examined by flow cytometry. Results S100A8, but not high mobility group box 1 (HMGB1), in the eye was found to be correlated with intraocular inflammatory episodes. Administration of paquinimod significantly protected tEAU rats from recurrence. Treated tEAU rats had fewer R16-specific Th1 and Th17 cells, but increased numbers of Tregs. R16-specific T cells from treated tEAU rats into naïve recipients prevented induction of tEAU by R16-specific T cells from nontreated tEAU rats. Moreover, APCs from treated tEAU rats expressed higher levels of a negative costimulatory molecule, CD200R, and lower levels of CD80, CD86, and MHC class II molecules compared to APCs from nontreated tEAU rats. An opposite pattern of expression of these molecules was observed on APCs incubated in vitro with recombinant S100A8. Conclusions Our data demonstrate a link between local expression of DAMPs and autoimmune responses, and suggest that complete S100A8/A9 blockade may be a new therapeutic target in recurrent autoimmune uveitis. PMID:29625456

  14. Dry eye disease and uveitis: A closer look at immune mechanisms in animal models of two ocular autoimmune diseases.

    PubMed

    Bose, Tanima; Diedrichs-Möhring, Maria; Wildner, Gerhild

    2016-12-01

    Understanding the immunopathogenesis of autoimmune and inflammatory diseases is a prerequisite for specific and effective therapeutical intervention. This review focuses on animal models of two common ocular inflammatory diseases, dry eye disease (DED), affecting the ocular surface, and uveitis with inflammation of the inner eye. In both diseases autoimmunity plays an important role, in idiopathic uveitis immune reactivity to intraocular autoantigens is pivotal, while in dry eye disease autoimmunity seems to play a role in one subtype of disease, Sjögren' syndrome (SjS). Comparing the immune mechanisms underlying both eye diseases reveals similarities, and significant differences. Studies have shown genetic predispositions, T and B cell involvement, cytokine and chemokine signatures and signaling pathways as well as environmental influences in both DED and uveitis. Uveitis and DED are heterogeneous diseases and there is no single animal model, which adequately represents both diseases. However, there is evidence to suggest that certain T cell-targeting therapies can be used to treat both, dry eye disease and uveitis. Animal models are essential to autoimmunity research, from the basic understanding of immune mechanisms to the pre-clinical testing of potential new therapies. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Equine recurrent uveitis--a spontaneous horse model of uveitis.

    PubMed

    Deeg, Cornelia A; Hauck, Stefanie M; Amann, Barbara; Pompetzki, Dirk; Altmann, Frank; Raith, Albert; Schmalzl, Thomas; Stangassinger, Manfred; Ueffing, Marius

    2008-01-01

    Equine recurrent uveitis (ERU) is an autoimmune disease that occurs with a high prevalence (10%) in horses. ERU represents the only reliable spontaneous model for human autoimmune uveitis. We already identified and characterized novel autoantigens (malate dehydrogenase, recoverin, CRALBP) by analyzing the autoantibody-binding pattern of horses affected by spontaneous recurrent uveitis (ERU) to the retinal proteome. CRALBP also seems to be relevant to human autoimmune uveitis. Proteomic screening of vitreous and retinal samples from ERU diseased cases in comparison to healthy controls has led to the identification of a series of differentially regulated proteins, which are functionally linked to the immune system and the maintenance of the blood-retinal barrier. 2008 S. Karger AG, Basel.

  16. Immunomodulatory effects of Longdan Xiegan Tang on CD4+/CD8+ T cells and associated inflammatory cytokines in rats with experimental autoimmune uveitis.

    PubMed

    Tang, Kai; Guo, Dadong; Zhang, Lian; Guo, Junguo; Zheng, Fengming; Si, Junkang; Bi, Hongsheng

    2016-09-01

    Longdan Xiegan Tang (LXT) is a mixture of herbal extracts commonly used in traditional Chinese medicine that may exert immunomodulatory effects for the treatment of autoimmune diseases. However, the detailed mechanisms that mediate the actions of LXT are unclear. The present study induced an experimental autoimmune uveitis (EAU) model in Lewis rats via injection of IRBP1177‑1191 emulsion. The model was used to investigate the effects of LXT on EAU rats and assess the efficacy of LXT by measuring clinical manifestations and histopathological changes caused by EAU. Additionally, alterations in the ratio of CD4+/CD8+‑T cells were determined by flow cytometry, and the expression of interferon (IFN)‑γ, interleukin (IL)‑17, IL‑10 and tumor necrosis factor (TNF)‑α were measured using reverse transcription‑quantitative polymerase chain reaction and enzyme‑linked immunosorbent assay analysis. The results of the present study demonstrate that LXT can efficiently alleviate the symptoms of EAU, inhibit the differentiation of uveitogenic CD4+ T cells and reduce the expression of proinflammatory cytokines, including IFN‑γ, IL‑17 and TNF‑α. Furthermore, LXT promotes the production of IL‑10 and accelerates the recovery of EAU, indicating that the immunomodulatory effects of LXT may potentially be used for the treatment of uveitis.

  17. Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis.

    PubMed

    Simonini, Gabriele; Bracaglia, Claudia; Cattalini, Marco; Taddio, Andrea; Brambilla, Alice; De Libero, Cinzia; Pires Marafon, Denise; Caputo, Roberto; Cimaz, Rolando

    2017-06-01

    To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment. A retrospective, multicenter, cohort study. Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43). Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

  18. Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Decrease the Development of Severe Experimental Autoimmune Uveitis in B10.RIII Mice.

    PubMed

    Qin, Yu; Chan, Ann M; Chang, Yu-Ling; Matynia, Anna; Kouris, Nicholas A; Kimbrel, Erin A; Ashki, Negin; Parikh, Sachin; Gorin, Michael B; Lanza, Robert; Levinson, Ralph D; Gordon, Lynn K

    2017-09-15

    We investigated the effect of exogenously administered human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) in experimental autoimmune uveitis (EAU) in B10.RIII mice, a murine model of severe uveitis. B10.RIII mice were immunized with an uveitogenic peptide, and intraperitoneal injections of 5 million hESC-MSCs per animal were given on the same day. Behavioral light sensitivity assays, histological evaluation, cytokine production, and regulatory T cells were analyzed at the peak of the disease. Histological and behavioral evidence demonstrated that early systemic treatment with hESC-MSCs decreases the development of severe EAU in B10.RIII mice. hESC-MSCs suppress Th17 and upregulate Th1 and Th2 responses as well as IL-2 and GM-CSF in splenocytes from hESC-MSC-treated mice. MSCs that originate from hESC decrease the development of severe EAU in B10.RIII mice, likely through systemic immune modulation. Further investigation is needed to determine any potential effect on active EAU.

  19. Proteome Dynamics in Biobanked Horse Peripheral Blood Derived Lymphocytes (PBL) with Induced Autoimmune Uveitis.

    PubMed

    Hauck, Stefanie M; Lepper, Marlen F; Hertl, Michael; Sekundo, Walter; Deeg, Cornelia A

    2017-10-01

    Equine recurrent uveitis is the only spontaneous model for recurrent autoimmune uveitis in humans, where T cells target retinal proteins. Differences between normal and autoaggressive lymphocytes were identified in this study by analyzing peripheral blood derived lymphocytes (PBL) proteomes from the same case with interphotoreceptor retinoid binding protein induced uveitis sampled before (Day 0), during (Day 15), and after uveitic attack (Day 23). Relative protein abundances of PBL were investigated in a quantitative, label-free differential proteome analysis in cells that were kept frozen for 14 years since the initial experiment. Quantitative data could be acquired for 2632 proteins at all three time points. Profound changes (≥2-fold change) in PBL protein abundance were observed when comparing Day 0 with 15, representing acute inflammation (1070 regulated proteins) and Day 0 with 23 (cessation; 1571 regulated). Significant differences applied to proteins with functions in integrin signaling during active uveitis, involving "Erk and pi-3 kinase are necessary for collagen binding in corneal epithelia," "integrins in angiogenesis," and "integrin-linked kinase signaling" pathways. In contrast, at cessation of uveitic attack, significantly changed proteins belonged to pathways of "nongenotropic androgen signaling," "classical complement pathway," and "Amb2 integrin signaling." Several members of respective pathways were earlier shown to be changed in naturally occurring uveitis, underscoring the significance of these findings here and proofing the value of the induced model in mimicking spontaneous autoimmune uveitis. All MS data have been deposited to the ProteomeXchange consortium via the PRIDE partner repository (dataset identifier PXD005580). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Multiple etiologies of equine recurrent uveitis--A natural model for human autoimmune uveitis: A brief review.

    PubMed

    Witkowski, Lucjan; Cywinska, Anna; Paschalis-Trela, Katarzyna; Crisman, Mark; Kita, Jerzy

    2016-02-01

    Equine recurrent uveitis (ERU) has various etiologies, with Leptospira infection and genetic predisposition being the leading risk factors. Regardless of etiology, expression of ocular proteins associated with maintenance of the blood-ocular barrier is impaired in ERU. The recurring-remitting cycle of ERU repeatedly disrupts the blood-ocular barrier, allowing the previously immune-privileged ocular environment to become the site of a progressive local autoimmune pathology that ultimately results in tissue destruction and vision loss. The immune-mediated process involves humoral and cellular mechanisms. Intraocular antibodies either produced in the eye or that leak through the blood-ocular barrier, are often present at higher levels than in serum and react with antigens in ocular tissue of horses with ERU. Ocular infiltration of auto-aggressive lymphocytes occurs with each uveitis episode and is the most crucial contributor to inflammation and eye damage. Recurring uveitis episodes may be initiated when epitopes of an ocular antigen become visible to the immune system (intramolecular spreading) or another autoantigen (intermolecular spreading), resulting in a new inflammatory reaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Expression changes and novel interaction partners of talin 1 in effector cells of autoimmune uveitis.

    PubMed

    Degroote, Roxane L; Hauck, Stefanie M; Treutlein, Gudrun; Amann, Barbara; Fröhlich, Kristina J H; Kremmer, Elisabeth; Merl, Juliane; Stangassinger, Manfred; Ueffing, Marius; Deeg, Cornelia A

    2013-12-06

    Autoimmune uveitis is characterized by crossing of blood-retinal barrier (BRB) by autoaggressive immune cells. Equine recurrent uveitis (ERU) is a valuable spontaneous model for autoimmune uveitis and analyses of differentially expressed proteins in ERU unraveled changed protein clusters in target tissues and immune system. Healthy eyes are devoid of leukocytes. In ERU, however, leukocytes enter the inner eye and subsequently destroy it. Molecular mechanisms enabling cell migration through BRB still remain elusive. Previously, we detected decreased talin 1 expression in blood-derived granulocytes of ERU cases, linking the innate immune system to ERU. Because changes in leukocyte protein expression pattern may play a role in pathological abnormalities leading to migration ability, we aimed at identifying interactors of talin 1 in leukocytes with immunoprecipitation, followed by LC-MS/MS for candidate identification. This enabled us to identify CD90 (Thy1) as novel interactor of talin 1 besides several other interactors. In blood-derived granulocytes from healthy individuals, CD90 was highly abundant and significantly reduced in ERU, especially in effector cells. Connection between talin 1 and CD90 and their expression differences in inflammation is an interesting novel finding allowing deeper insight into immune response of innate immune system and granulocyte migration ability in this organ-specific autoimmune disease.

  2. Pinealitis accompanying equine recurrent uveitis.

    PubMed Central

    Kalsow, C M; Dwyer, A E; Smith, A W; Nifong, T P

    1993-01-01

    There is no direct verification of pineal gland involvement in human uveitis. Specimens of pineal tissue are not available during active uveitis in human patients. Naturally occurring uveitis in horses gives us an opportunity to examine tissues during active ocular inflammation. We examined the pineal gland of a horse that was killed because it had become blind during an episode of uveitis. The clinical history and histopathology of the eyes were consistent with post-leptospiral equine recurrent uveitis. The pineal gland of this horse had significant inflammatory infiltration consisting mainly of lymphocytes with some eosinophils. This observation of pinealitis accompanying equine uveitis supports the animal models of experimental autoimmune uveoretinitis with associated pinealitis and suggests that the pineal gland may be involved in some human uveitides. Images PMID:8435400

  3. Altered expression of talin 1 in peripheral immune cells points to a significant role of the innate immune system in spontaneous autoimmune uveitis.

    PubMed

    Degroote, Roxane L; Hauck, Stefanie M; Kremmer, Elisabeth; Amann, Barbara; Ueffing, Marius; Deeg, Cornelia A

    2012-07-19

    The molecular mechanism which enables activated immune cells to cross the blood-retinal barrier in spontaneous autoimmune uveitis is yet to be unraveled. Equine recurrent uveitis is the only spontaneous animal model allowing us to investigate the autoimmune mediated transformation of leukocytes in the course of this sight threatening disease. Hypothesizing that peripheral blood immune cells change their protein expression pattern in spontaneous autoimmune uveitis, we used DIGE to detect proteins with altered abundance comparing peripheral immune cells of healthy and ERU diseased horses. Among others, we found a significant downregulation of talin 1 in peripheral blood granulocytes of ERU specimen, pointing to changes in β integrin activation and indicating a significant role of the innate immune system in spontaneous autoimmune diseases. Copyright © 2012. Published by Elsevier B.V.

  4. CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas.

    PubMed

    Deininger, M H; Zhao, Y; Schluesener, H J

    1999-01-01

    CP-10 (chemotactic protein of m.w. 10,000) is a member of the S100 superfamily of Ca2+ binding peptides, which has potent chemotactic activity for murine and human myeloid cells. Here we report on the generation of monoclonal antibodies against CP-10 and accumulation of CP-10+ cells during experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), uveitis (EAU) and in experimentally transplanted C6 gliomas. During acute inflammation, CP-10 is mainly expressed by large ED1+ monocytic perivascular cells that accumulate at days 11-14. CP-10+ cells are predominantly located in areas of cellular infiltration but are as well found in the meninges and infiltrating the brain parenchyma. In transplanted gliomas, CP-10+ cells are located exclusively within the tumor parenchyma. Using double labeling experiments, other cells participating in the inflammatory reaction were found to express CP-10, like few lymphoblastic W3/13+ cells in the vicinity of the inflammatory infiltrate.

  5. Serum PEDF levels are decreased in a spontaneous animal model for human autoimmune uveitis.

    PubMed

    Zipplies, Johanna K; Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Ueffing, Marius; Deeg, Cornelia A

    2009-02-01

    Identification of biomarkers is of critical relevance toward improving diagnosis and therapy of autoimmune disorders. Serum markers are a desirable choice as sera are easily accessible and the development of assays for routine clinical detection prompts feasible. Autoimmune uveitis, a recurrent disease affecting the eye, is characterized by returning inflammatory attacks of the inner eye followed by variable periods of quiescent stages. Spontaneous equine recurrent uveitis (ERU) is the equine equivalent and serves as a model for the human disease. To identify potential biomarker candidates, we first systematically compared the proteomes of individual ERU cases with healthy controls by proteomic profiling using 2-D difference-gel-electrophoresis (2-D DIGE) followed by tandem mass spectrometry. A total of seven differentially expressed proteins were identified. Besides the upregulation of IgG and the significant lower expression of albumin, Antithrombin III, and Vitamin D binding protein, we found complement components C1q and C4, to be downregulated in uveitic state. Interestingly, Pigment epithelium-derived factor (PEDF), a marker already detected by 2DE differential proteome analysis in ERU target tissues, vitreous and retina, was found to be also significantly downregulated in sera. The lower expression of PEDF in sera of horses with uveitis could be verified in a cohort of 116 ERU cases and 115 healthy controls. Our findings of a significant lower PEDF expression in ERU cases also in the periphery of the eye proves PEDF as a promising uveitis biomarker.

  6. Long-Term Therapeutic Effects of Mesenchymal Stem Cells Compared to Dexamethasone on Recurrent Experimental Autoimmune Uveitis of Rats

    PubMed Central

    Zhang, Lingjun; Zheng, Hui; Shao, Hui; Nian, Hong; Zhang, Yan; Bai, Lingling; Su, Chang; Liu, Xun; Dong, Lijie; Li, Xiaorong; Zhang, Xiaomin

    2014-01-01

    Purpose. We tested the long-term effects of different regimens of mesenchymal stem cell (MSC) administration in a recurrent experimental autoimmune uveitis (rEAU) model in rats, and compared the efficacy of MSC to that of dexamethasone (DEX). Methods. One or two courses of MSC treatments were applied to R16-specific T cell–induced rEAU rats before or after disease onsets. The DEX injections were given for 7 or 50 days continuously after disease onsets. Clinical appearances were observed until the 50th day after transfer. On the 10th day, T cells from control and MSC groups were analyzed by flow cytometry. Supernatants from the proliferation assay and aqueous humor were collected for cytokine detection. Functions of T cells and APCs in spleens also were studied by lymphocyte proliferation assays. Results. One course of MSC therapy, administered after disease onset, led to a lasting therapeutic effect, with a decreased incidence, reduced mean clinical score, and reduced retinal impairment after 50 days of observation, while multiple courses of treatment did not improve the therapeutic benefit. Although DEX and MSCs equally reduced the severity of the first episode of rEAU, the effect of DEX was shorter lasting, and DEX therapy failed to control the disease even with long periods of treatment. The MSCs significantly decreased T helper 1 (Th1) and Th17 responses, suppressed the function of antigen-presenting cells, and upregulated T regulatory cells. Conclusions. These results suggested that MSCs might be new corticosteroid spring agents, while providing fewer side effects and longer lasting suppressive effects for recurrent uveitis. PMID:25125599

  7. Osteopontin and fibronectin levels are decreased in vitreous of autoimmune uveitis and retinal expression of both proteins indicates ECM re-modeling.

    PubMed

    Deeg, Cornelia A; Eberhardt, Christina; Hofmaier, Florian; Amann, Barbara; Hauck, Stefanie M

    2011-01-01

    Autoimmune uveitis is an intraocular inflammation that arises through autoreactive T-cells attacking the inner eye, eventually leading to blindness. However, the contributing molecular pathomechanisms within the affected tissues remain as yet elusive. The extracellular matrix (ECM) is a highly dynamic structure that varies tremendously and influences the encompassing tissue. In order to assess ECM re-modeling in autoimmune uveitis, we investigated the expression of ECM molecules fibronectin and osteopontin in vitreous and retina samples. This was carried out in the only spontaneous animal model for human autoimmue uveitis, namely equine recurrent uveitis (ERU) that resembles the human disease in clinical as well as in immunopathological aspects. ERU is a naturally occurring autoimmune disease in horses that develops frequently and has already proved its value to study disease-related pathomechanisms. Western blot analysis of fibronectin and osteopontin in healthy and uveitic vitreous revealed significant reduction of both proteins in uveitis. Immunohistochemical expression of fibronectin in healthy retinas was restricted to the inner limiting membrane abutting vimentin positive Müller cell endfeet, while in uveitic sections, a disintegration of the ILM was observed changing the fibronectin expression to a dispersed pattern extending toward the vitreous. Retinal expression of osteopontin in control tissue was found in a characteristic Müller cell pattern illustrated by co-localization with vimentin. In uveitic retinas, the immunoreactivity of osteopontin in gliotic Müller cells was almost absent. The ability of Müller cells to express fibronectin and osteopontin was additionally shown by immunocytochemistry of primary cultured equine Müller cells and the equine Müller cell line eqMC-7. In conclusion, severe ECM re-modeling in autoimmune uveitis reported here, might affect the adhesive function of fibronectin and thus the anchoring of Müller cell endfeet to

  8. Formin like 1 expression is increased on CD4+ T lymphocytes in spontaneous autoimmune uveitis.

    PubMed

    Degroote, Roxane L; Uhl, Patrizia B; Amann, Barbara; Krackhardt, Angela M; Ueffing, Marius; Hauck, Stefanie M; Deeg, Cornelia A

    2017-02-10

    The membrane protein expression repertoire of cells changes in course of activation. In equine recurrent uveitis (ERU), a spontaneous autoimmune disease in horses with relapsing and ultimately blinding inner eye inflammation, CD4+ T lymphocytes are the crucial pathogenic cells activated in the periphery directly prior to an inflammatory episode. In order to find relevant changes in the membrane proteome associated to disease, we sorted CD4+ lymphocytes and compared protein abundance from the generated proteome datasets of both healthy horses and ERU cases. We detected formin like 1, a key player in actin dependent cellular processes such as phagocytosis, cell adhesion and cell migration, with significantly higher abundance in the CD4+ cell membrane proteome of horses with ERU. In transmigration experiments, we demonstrated higher migration rate of cells originating from diseased animals connecting formin like 1 to the migratory ability of cells. These findings are the first description of formin like 1 in association to processes involved in migration of inflammatory CD4+ T cells across the blood-retinal barrier in a spontaneous ocular autoimmune disease and suggest formin like 1 to play a role in the molecular mechanisms of ERU disease pathogenesis. Data are available via ProteomeXchange with identifier PXD005384. This comparative proteomic study of membrane proteins of CD4+ T cells identified a novel protein, formin like 1, with expression on the plasma cell membrane of equine CD4+ T cells and a significant change of abundance on CD4+ T cells of horses with a spontaneous autoimmune disease. Functional studies in a cell culture model for transmigration at the blood-retinal barrier (BRB) unraveled a strong impact of formin like 1 on migratory processes of CD4+ T cells across the BRB, a key event in uveitis pathogenesis. These findings provide novel knowledge about changes in the CD4+ immune cell membrane proteome in a spontaneously and naturally occurring

  9. In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis.

    PubMed

    Gutowski, Michal B; Wilson, Leslie; Van Gelder, Russell N; Pepple, Kathryn L

    2017-03-01

    We develop a quantitative bioluminescence assay for in vivo longitudinal monitoring of inflammation in animal models of uveitis. Three models of experimental uveitis were induced in C57BL/6 albino mice: primed mycobacterial uveitis (PMU), endotoxin-induced uveitis (EIU), and experimental autoimmune uveitis (EAU). Intraperitoneal injection of luminol sodium salt, which emits light when oxidized, provided the bioluminescence substrate. Bioluminescence images were captured by a PerkinElmer In Vivo Imaging System (IVIS) Spectrum and total bioluminescence was analyzed using Living Image software. Bioluminescence on day zero was compared to bioluminescence on the day of peak inflammation for each model. Longitudinal bioluminescence imaging was performed in EIU and EAU. In the presence of luminol, intraocular inflammation generates detectable bioluminescence in three mouse models of uveitis. Peak bioluminescence in inflamed PMU eyes (1.46 × 105 photons/second [p/s]) was significantly increased over baseline (1.47 × 104 p/s, P = 0.01). Peak bioluminescence in inflamed EIU eyes (3.18 × 104 p/s) also was significantly increased over baseline (1.09 × 104 p/s, P = 0.04), and returned to near baseline levels by 48 hours. In EAU, there was a nonsignificant increase in bioluminescence at peak inflammation. In vivo bioluminescence may be used as a noninvasive, quantitative measure of intraocular inflammation in animal models of uveitis. Primed mycobacterial uveitis and EIU are both acute models with robust anterior inflammation and demonstrated significant changes in bioluminescence corresponding with peak inflammation. Experimental autoimmune uveitis is a more indolent posterior uveitis and generated a more modest bioluminescent signal. In vivo imaging system bioluminescence is a nonlethal, quantifiable assay that can be used for monitoring inflammation in animal models of uveitis.

  10. Mesenchymal stem cells induce functionally active T-regulatory lymphocytes in a paracrine fashion and ameliorate experimental autoimmune uveitis.

    PubMed

    Tasso, Roberta; Ilengo, Cristina; Quarto, Rodolfo; Cancedda, Ranieri; Caspi, Rachel R; Pennesi, Giuseppina

    2012-02-01

    Mesenchymal stem/progenitor cells (MSCs) have regenerative and immunomodulatory properties, exerted by cell-cell contact and in a paracrine fashion. Part of their immunosuppressive activity has been ascribed to their ability to promote the induction of CD4+CD25+FoxP3+ T lymphocytes with regulatory functions (Treg). Here the authors studied the effect of MSCs on the induction of Treg and on the development of autoimmunity, and they examined the possibility that MSC-mediated Treg induction could be attributed to the secretion of soluble factors. The authors induced experimental autoimmune uveitis (EAU) in mice by immunization with the 1-20 peptide of the intraphotoreceptor binding protein. At the same time, some of the animals were treated intraperitoneally with syngeneic MSCs. The authors checked T-cell responses and in vitro Treg conversion by cell proliferation and blocking assays, in cell-cell contact and transwell settings. TGFβ and TGFβ receptor gene expression analyses were performed by real-time PCR. The authors found that a single intraperitoneal injection of MSCs was able to significantly attenuate EAU and that a significantly higher percentage of adaptive Treg was present in MSC-treated mice than in MSC-untreated animals. In vitro blocking of antigen presentation by major histocompatibility complex class II precluded priming and clonal expansion of antigen-specific Treg, whereas blockade of TGFβ impaired the expression of FoxP3, preventing the conversion of CD4+ T cells into functionally active Treg. The authors demonstrated that MSCs can inhibit EAU and that their immunomodulatory function is due at least in part to the induction of antigen-specific Treg in a paracrine fashion by secreting TGFβ.

  11. Vitreal IgM autoantibodies target neurofilament medium in a spontaneous model of autoimmune uveitis.

    PubMed

    Swadzba, Margarete E; Hirmer, Sieglinde; Amann, Barbara; Hauck, Stefanie M; Deeg, Cornelia A

    2012-01-25

    Although the presence of IgG autoantibodies in the vitreous of spontaneous cases of equine recurrent uveitis (ERU) has been demonstrated, the potential role of IgM reactivities during ERU pathogenesis remains unexplored. The purpose of this study was to examine the presence of IgM autoantibodies in vitreous specimens of ERU-affected horses and to test their binding specificity to intraocularly expressed proteins. To test IgM autoantibody responses to retinal tissue, vitreous samples of eye-healthy controls and ERU patients were analyzed via two-dimensional Western blot analysis with equine retinal tissue as an antigen source. A candidate protein, the peptide neurofilament medium (NF-M), was identified via mass spectrometry and validated via enzyme-linked immunosorbent assay. Immunohistochemistry for NF-M expression was performed on healthy and ERU-affected retinal sections. Whereas autoreactivity was never detected in the healthy vitreous samples, NF-M was specifically targeted by vitreal IgM autoantibodies in 44% of the ERU cases. Vitreal anti-NF-M IgG was detected in only 8% of the ERU samples, pointing to a persistent IgM response. In healthy horse retina, NF-M was located in the retinal ganglion cells and their processes, with additional staining in the outer plexiform layer. NF-M expression in ERU-affected retinas decreased considerably, and the remaining expression was limited to the nerve fiber layer. Intraocular anti NF-M IgM autoantibodies occur with high prevalence in vitreous of spontaneous autoimmune uveitis cases. The IgM dominated response may indicate a thymus-independent response to NF-M and merits further investigation in ERU, as well as in its human counterpart, autoimmune uveitis.

  12. Immunopathology of pineal glands from horses with uveitis.

    PubMed

    Kalsow, C M; Dubielzig, R R; Dwyer, A E

    1999-06-01

    Pinealitis accompanying uveitis is well established in laboratory models of experimental autoimmune uveoretinitis. In naturally occurring uveitis, pinealitis has been demonstrated in the pineal gland from a mare with active uveitis and is suspected in some human uveitides. We have evaluated pineal glands from horses with various stages of uveitis for signs of immunopathology accompanying spontaneous uveitis. Pineal glands from 10 horses with uveitis and from 13 horses without uveitis were evaluated for histochemical (H&E, collagen) and immunohistochemical (MHC class II antigen expression, infiltration of T and B lymphocytes, and glial fibrillary acidic protein (GFAP) and vimentin upregulation) evidence of inflammation. Septal areas of pineal glands from horses with uveitis had clusters of MHC class II antigen-expressing cells, T lymphocytes, and enhanced collagen deposition. These changes were not as readily observed in pineal glands from horses without uveitis. B lymphocytes were detected only in the pineal gland from the one mare with active uveitis in which T and B lymphocytes were organized into follicles. No differences in GFAP or vimentin immunoreactivity were noted in pineal glands from horses with or without uveitis. These pineal gland changes suggest that the pinealitis associated with equine uveitis is transient just as the uveitis of these horses is recurrent. Study of pineal glands from horses with clinically documented uveitis allows demonstration of subtle pineal changes associated with natural uveitis. Similar changes would be difficult to document in human patient populations.

  13. Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice.

    PubMed

    Yadav, Umesh C S; Shoeb, Mohammed; Srivastava, Satish K; Ramana, Kota V

    2011-10-17

    To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ∼2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.

  14. Blockade of the interaction of leukotriene b4 with its receptor prevents development of autoimmune uveitis.

    PubMed

    Liao, Tianjiang; Ke, Yan; Shao, Wen-Hai; Haribabu, Bodduluri; Kaplan, Henry J; Sun, Deming; Shao, Hui

    2006-04-01

    To investigate the role of leukotriene B4 (LTB4) and its receptor BLT1 in the pathogenesis of mouse uveitis. Experimental autoimmune uveitis (EAU) was induced in B10RIII mice by immunization of interphotoreceptor retinoid binding protein (IRBP; peptide sequence 161-180) or in C57BL/6 (B6) mice by transfer of activated T cells specific for IRBP1-20. The animals were then treated with and without the BLT1 receptor antagonist, CP105696, at the disease onset after immunization or at day 0 or day 6 after T-cell transfer. EAU was also induced in wild-type B6 (WT) and BLT1-deficient (BLT1-/-) mice by reciprocal transfer of the T cells from B6 to BLT1-deficient mice and vise versa. Clinical signs of inflammation and ocular histology were compared. The chemotactic activity of LTB4 on naïve and IRBP-specific autoreactive T cells as well as effector leukocytes was examined. The treatment of CP105696, greatly reduced the intensity of ongoing disease. IRBP1-20-specific T cells derived from wild-type B6 mice induced only mild uveitis in syngeneic BLT1-deficient mice and that IRBP1-20-specific T cells derived from BLT1-/- mice induced milder disease in wild-type B6 mice than those derived from wild-type B6 mice, suggesting that expression of the LTB4 receptor on both activated autoreactive T cells and effector leukocytes was necessary for ocular inflammation to occur. Consistent with these data, transfer of autoreactive T cells from B6 mice to 5-lipoxygenase-deficient (5-LO-/-) mice, which have a functional defect in LTB4 expression, also failed to induce uveitis in the recipient mice. The results demonstrate a critical role for LTB4 in ocular inflammation and in the development and progression of EAU and suggest a new potential target for therapeutic intervention in this disease.

  15. Uveitis and Gender: The Course of Uveitis in Pregnancy

    PubMed Central

    Chiam, Nathalie P. Y.; Lim, Lyndell L. P.

    2014-01-01

    The hormonal and immunological changes in pregnancy have a key role in maintaining maternal tolerance of the semiallogeneic foetus. These pregnancy-associated changes may also influence the course of maternal autoimmune diseases. Noninfectious uveitis tends to improve during pregnancy. Specifically, uveitis activity tends to ameliorate from the second trimester onwards, with the third trimester being associated with the lowest disease activity. The mechanism behind this phenomenon is likely to be multifactorial and complex. Possible mechanisms include Th1/Th2 immunomodulation, regulatory T-cell phenotype plasticity, and immunosuppressive cytokines. This clearly has management implications for patients with chronic sight threatening disease requiring systemic treatment, as most medications are not recommended during pregnancy due to lack of safety data or proven teratogenicity. Given that uveitis activity is expected to decrease in pregnancy, systemic immunosuppressants could be tapered during pregnancy in these patients, with flare-ups being managed with local corticosteroids till delivery. In the postpartum period, as uveitis activity is expected to rebound, patients should be reviewed closely and systemic medications recommenced, depending on uveitis activity and the patient's breastfeeding status. This review highlights the current understanding of the course of uveitis in pregnancy and its management to help guide clinicians in managing their uveitis patients during this special time in life. PMID:24683491

  16. Cyclosporine: A Historical Perspective on Its Role in the Treatment of Noninfectious Uveitis.

    PubMed

    Smith, Wendy M

    2017-05-01

    The history of cyclosporine and uveitis is intertwined with the development of experimental autoimmune uveitis (EAU) animal models and the understanding that T lymphocytes play a major role in the pathogenesis of uveitis. The early studies of CsA in uveitis also demonstrated the power of collaborative efforts in translational research. Dr. Robert Nussenblatt and his colleagues were the first to show that CsA can inhibit EAU. Over many years after the initial CsA experiments, Dr. Nussenblatt's group as well as others continued to study CsA under experimental conditions as well as in clinical trials with human patients. The data and observations from these studies significantly advanced our knowledge of uveitis pathophysiology and demonstrated the value of well-designed masked, controlled treatment trials in uveitis. Dr. Nussenblatt and his collaborators delved into the most significant adverse effect of CsA, renal toxicity, and helped elucidate the pathophysiology of renal injury. They explored adjunctive treatments to improve the efficacy and decrease the toxicity of CsA and also studied other members of the cyclosporine family. Among the immunosuppressives used to treat ocular inflammation, CsA was the first, and remains the only medication comprehensively studied under both experimental and clinical conditions.

  17. Regulatory T Cell Therapy for Uveitis: A New Promising Challenge.

    PubMed

    Foussat, Arnaud; Gregoire, Sylvie; Clerget-Chossat, Nathalie; Terrada, Celine; Asnagli, Hélène; Lemoine, François M; Klatzmann, David; LeHoang, Phuc; Forte, Miguel; Bodaghi, Bahram

    2017-05-01

    Uveitis is a sight-threatening primary intraocular inflammation of various origins in mainly young and active patients. Due to the absence of biomarkers in most of the cases, the current treatment of noninfectious entities remains nonspecific, using corticosteroids, conventional immunosuppressors, and more recently biological agents. Identification of regulatory T cells in different models of autoimmune uveitis together with the evaluation of this important subpopulation in different entities paved the way for new therapeutic strategies, in addition to exclusive pharmaceutical approaches. Upregulation of regulatory T cells induced by biological agents has been recently highlighted. Development of cell therapy in autoimmune diseases is at its stammering needing more experimental data and robust clinical trials to demonstrate safety and efficacy before larger developments. Specific or polyclonal Tregs may be used, but it is of utmost importance to determine the method of selection, the level of activation, and the route of administration. Mastering immune cell therapy remains a challenging goal in patients with autoimmune diseases, but it may significantly enlarge our therapeutic possibilities in severe and refractory situations.

  18. [Tubulointerstitial nephritis with uveitis (TINU) syndrome. A relatively rare rheumatological differential diagnosis with unexplained uveitis].

    PubMed

    Häusler, U; Guminski, B; Helmchen, U; Kisters, K; Heinz, C; Braun, J

    2013-05-01

    The tubulo-interstitial nephritis and uveitis (TINU) syndrome, first described in 1975, is a rare disease most probably of autoimmune origin that is characterized by unilateral or bilateral uveitis and tubulointerstitial nephritis. Most patients are adolescents and it is sometimes associated with other autoimmune diseases, such as spondyloarthritis, rheumatoid arthritis and hyperthyroidosis. This article reports the case of a 43-year-old female patient who presented with refractory recurrent bilateral uveitis despite therapy with high doses of corticosteroids in combination with cyclosporin. When the patient was referred to this hospital for rheumatological examination after almost 1 year of therapy, mild renal insufficiency and proteinuria were found. The kidney biopsy revealed interstitial nephritis, partly crescent-shaped and partly chronic. A diagnosis of TINU syndrome was made and treatment with adalimumab in combination with methotrexate was started. The favorable clinical outcome indicated that tumor necrosis factor (TNF) alpha may play an important role in the pathogenesis of TINU syndrome.

  19. [Treatment of posterior noninfectious uveitis : Current situation and future developments].

    PubMed

    Pleyer, U; Pohlmann, D; Stübiger, N

    2016-05-01

    Treatment of autoimmune diseases has undergone significant changes and developments in recent years. New classes of active substances, in particular biologics and small molecules have resulted in previously unknown success in the treatment of many diseases. In particular patients suffering from autoimmune rheumatic or dermatological diseases have benefited. For autoimmune uveitis there are numerous reports indicating excellent therapeutic and preventive effects; however, statutory approval for therapy in adults is still pending. This article outlines recent advances and future therapeutic options for the treatment of posterior segment noninfectious uveitis.

  20. Current therapeutic approaches to autoimmune chronic uveitis in children.

    PubMed

    Simonini, Gabriele; Cantarini, Luca; Bresci, Cecilia; Lorusso, Monica; Galeazzi, Mauro; Cimaz, Rolando

    2010-08-01

    Uveitis is an inflammatory disorder involving inflammation of the uveal tract. It is classified as anterior, intermediate, posterior or panuveitis, depending on the part of eye affected by the inflammatory process. In children, non-infectious, chronic uveitis is a relatively uncommon but serious disease, with the potential for significant long-term complications and possible blindness. Although frequently associated with an underlying systemic disease, e.g. juvenile idiopathic arthritis (JIA), a significant number of cases in children show no associated signs or symptoms, and are labelled as idiopathic. Taking into account this evidence, an anti-inflammatory therapy based on an immuno-modulatory approach seems a reasonable strategy for non-infectious chronic uveitis, in children as well as in adults. Due to a lack of controlled studies regarding uveitis in children, immunosuppressive drugs are supported only at evidence level III. The aim of this review is to report currently available medical strategies for treatment of childhood sight-threatening chronic uveitis; in addition, a step-by-step approach to the use of immunosuppressants in this context is suggested. 2010 Elsevier B.V. All rights reserved.

  1. Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a Model of Uveitis in Rats.

    PubMed

    Pepple, Kathryn L; Rotkis, Lauren; Van Grol, Jennifer; Wilson, Leslie; Sandt, Angela; Lam, Deborah L; Carlson, Eric; Van Gelder, Russell N

    2015-12-01

    The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats. In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays. Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU. Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and vitreous of both models and may be a

  2. Differential expression of inwardly rectifying K+ channels and aquaporins 4 and 5 in autoimmune uveitis indicates misbalance in Müller glial cell-dependent ion and water homeostasis.

    PubMed

    Eberhardt, Christina; Amann, Barbara; Feuchtinger, Annette; Hauck, Stefanie M; Deeg, Cornelia A

    2011-05-01

    Reactive gliosis is a well-established response to virtually every retinal disease. Autoimmune uveitis, a sight threatening disease, is characterized by recurrent relapses through autoaggressive T-cells. The purpose of this study was to assess retinal Müller glial cell function in equine recurrent uveitis (ERU), a spontaneous disease model resembling the human disease, by investigating membrane proteins implicated in ion and water homeostasis. We found that Kir2.1 was highly expressed in diseased retinas, whereas Kir4.1 was downregulated in comparison to controls. Distribution of Kir2.1 appeared Müller cell associated in controls, whereas staining of cell somata in the inner nuclear layer was observed in uveitis. In contrast to other subunits, Kir4.1 was evenly expressed along equine Müller cells, whereas in ERU, Kir4.1 almost disappeared from Müller cells. Hence, we suggest a different mechanism for potassium buffering in the avascular equine retina and, moreover, an impairment in uveitis. Uveitic retinas showed significantly increased expression of AQP4 as well as a displaced expression from Müller cells in healthy specimens to an intense circular expression pattern in the outer nuclear layer in ERU cases. Most interestingly, we detected the aquaporin family member protein AQP5 to be expressed in Müller cells with strong enrichments in Müller cell secondary processes. This finding indicates that fluid regulation within the equine retina may be achieved by an additional aquaporin. Furthermore, AQP5 was significantly decreased in uveitis. We conclude that the Müller cell response in autoimmune uveitis implies considerable changes in its potassium and water physiology.

  3. Clinical Trials in Noninfectious Uveitis

    PubMed Central

    Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

    2015-01-01

    The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

  4. Intraocular inflammation in autoimmune diseases.

    PubMed

    Pras, Eran; Neumann, Ron; Zandman-Goddard, Gisele; Levy, Yair; Assia, Ehud I; Shoenfeld, Yehuda; Langevitz, Pnina

    2004-12-01

    The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.

  5. In situ cell surface proteomics reveals differentially expressed membrane proteins in retinal pigment epithelial cells during autoimmune uveitis.

    PubMed

    Uhl, P B; Szober, C M; Amann, B; Alge-Priglinger, C; Ueffing, M; Hauck, S M; Deeg, C A

    2014-09-23

    Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye and plays an important role in pathogenesis of the sight threatening disease equine recurrent uveitis (ERU). ERU is a spontaneous autoimmune mediated inflammatory disease characterised by the breakdown of the outer blood-retinal barrier and an influx of autoaggressive T-cells into the inner eye. Therefore, identification of molecular mechanisms contributing to changed function of blood-retinal barrier in ERU is important for the understanding of pathophysiology. Cell surface proteins of RPE collected from healthy horses and horses with ERU were captured by in situ biotinylation and analysed with high resolution mass spectrometry coupled to liquid chromatography (LC-MS/MS) to identify differentially expressed proteins. With label free differential proteomics, a total of 27 differently expressed cell surface proteins in diseased RPE could be detected. Significant down-regulation of three very interesting proteins, synaptotagmin 1, basigin and collectrin was verified and further characterised. We applied an innovative and successful method to detect changes in the plasma cell surface proteome of RPE cells in a spontaneous inflammatory eye disease, serving as a valuable model for human autoimmune uveitis. We were able to identify 27 differentially expressed plasma cell membrane proteins, including synaptotagmin 1, basigin and collectrin, which play important roles in cell adhesion, transport and cell communication. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Equine recurrent uveitis: Human and equine perspectives.

    PubMed

    Malalana, Fernando; Stylianides, Amira; McGowan, Catherine

    2015-10-01

    Equine recurrent uveitis (ERU) is a spontaneous disease characterised by repeated episodes of intraocular inflammation. The epidemiology of ERU has not been fully elucidated, but the condition appears to be much more common in horses than is recurrent uveitis in humans, especially in certain breeds and geographical regions. Both humans and horses show a similarly altered immune response and a marked autoimmune response as the primary disease pathophysiology. However, an inciting cause is not always clear. Potential inciting factors in horses include microbial agents such as Leptospira spp. Microbial factors and genetic predisposition to the disease may provide clues as to why the horse appears so susceptible to this disease. The aim of this review is to discuss the immunology and genetics of ERU, compare the disease in horses with autoimmune anterior uveitis in humans, and discuss potential reasons for the increased prevalence in the horse. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a Model of Uveitis in Rats

    PubMed Central

    Pepple, Kathryn L.; Rotkis, Lauren; Van Grol, Jennifer; Wilson, Leslie; Sandt, Angela; Lam, Deborah L.; Carlson, Eric; Van Gelder, Russell N.

    2015-01-01

    Purpose The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats. Methods In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays. Results Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU. Conclusions Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and

  8. Identification and functional validation of novel autoantigens in equine uveitis.

    PubMed

    Deeg, Cornelia A; Pompetzki, Dirk; Raith, Albert J; Hauck, Stefanie M; Amann, Barbara; Suppmann, Sabine; Goebel, Thomas W F; Olazabal, Ursula; Gerhards, Hartmut; Reese, Sven; Stangassinger, Manfred; Kaspers, Bernd; Ueffing, Marius

    2006-08-01

    The development, progression, and recurrence of autoimmune diseases are frequently driven by a group of participatory autoantigens. We identified and characterized novel autoantigens by analyzing the autoantibody binding pattern from horses affected by spontaneous equine recurrent uveitis to the retinal proteome. Cellular retinaldehyde-binding protein (cRALBP) had not been described previously as autoantigen, but subsequent characterization in equine recurrent uveitis horses revealed B and T cell autoreactivity to this protein and established a link to epitope spreading. We further immunized healthy rats and horses with cRALBP and observed uveitis in both species with typical tissue lesions at cRALBP expression sites. The autoantibody profiling outlined here could be used in various autoimmune diseases to detect autoantigens involved in the dynamic spreading cascade or serve as predictive markers.

  9. Pharmacotherapy for uveitis: current management and emerging therapy

    PubMed Central

    Barry, Robert J; Nguyen, Quan Dong; Lee, Richard W; Murray, Philip I; Denniston, Alastair K

    2014-01-01

    Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual function for patients with the minimum possible side effects. PMID:25284976

  10. Juvenile idiopathic arthritis-associated uveitis.

    PubMed

    Clarke, Sarah L N; Sen, Ethan S; Ramanan, Athimalaipet V

    2016-04-27

    Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.

  11. Retinitis pigmentosa, Coats disease and uveitis.

    PubMed

    Solomon, A; Banin, E; Anteby, I; Benezra, D

    1999-01-01

    To study the anamnestic immune response to retinal specific antigens of two patients suffering from a rare triad of retinitis pigmentosa, Coats disease and uveitis. 17-year-old girl presented with an acute episode of panuveitis, and her 19-year-old brother suffered from chronic uveitis. On examination, both patients showed retinal vascular changes and subretinal exudations typical of Coats disease, with bone-spicule pigmentary changes as observed in retinitis pigmentosa. All routine examinations were unrevealing. However, the peripheral lymphocytes from these two siblings gave a specific anamnestic response to retinal antigens in vitro. A stimulation index of 4.6 was obtained when the sister's lymphocytes were stimulated with interphotoreceptor binding protein, IRBP--during the acute stage of the uveitis. The brother's lymphocytes showed a stimulation index of 2.7 towards S-Ag during the chronic phase of his uveitic condition. These results indicate that autoimmunity towards retinal antigens may play some role in specific types of retinitis pigmentosa. Whether these autoimmune reactions are a primary pathological mechanism or are secondary to the extensive destruction of the photoreceptor layer resulting from the retinitis pigmentosa remains debatable.

  12. Deciphering membrane-associated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry.

    PubMed

    Hauck, Stefanie M; Dietter, Johannes; Kramer, Roxane L; Hofmaier, Florian; Zipplies, Johanna K; Amann, Barbara; Feuchtinger, Annette; Deeg, Cornelia A; Ueffing, Marius

    2010-10-01

    Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well as autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling T cells to invade and attack the tissue have remained elusive. Changes in membrane protein expression patterns between diseased and healthy stages are especially interesting because initiating events of disease will most likely occur at membranes. Since disease progression is accompanied with a break-down of the blood-retinal barrier, serum-derived proteins mask the potential target tissue-related changes. To overcome this limitation, we used membrane-enriched fractions derived from retinas of the only available spontaneous animal model for the disease equine recurrent uveitis, and compared expression levels by a label-free LC-MSMS-based strategy to healthy control samples. We could readily identify a total of 893 equine proteins with 57% attributed to the Gene Ontology project term "membrane." Of these, 179 proteins were found differentially expressed in equine recurrent uveitis tissue. Pathway enrichment analyses indicated an increase in proteins related to antigen processing and presentation, TNF receptor signaling, integrin cell surface interactions and focal adhesions. Additionally, loss of retina-specific proteins reflecting decrease of vision was observed as well as an increase in Müller glial cell-specific proteins indicating glial reactivity. Selected protein candidates (caveolin 1, integrin alpha 1 and focal adhesion kinase) were validated by immunohistochemistry and tissue staining pattern pointed to a significant increase of these proteins at the level of the outer limiting membrane which is part of the outer blood-retinal barrier. Taken together, the membrane enrichment in combination with LC-MSMS-based label-free quantification greatly increased the sensitivity of the comparative tissue profiling and resulted in detection

  13. Impact of ghrelin on vitreous cytokine levels in an experimental uveitis model

    PubMed Central

    Turgut, Burak; Gül, Fatih Cem; Dağli, Ferda; Ilhan, Nevin; Özgen, Metin

    2013-01-01

    Background The purpose of this study was to investigate the effect of intraperitoneal ghrelin on vitreous levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) and to compare its effects with those of intraperitoneal infliximab in an experimental uveitis model. Methods Twenty-four male rats were assigned to four groups of six rats in each. All the rats, except for those in group 1 (controls), were injected intravitreally with concanavalin A to induce experimental uveitis. Rats in group 2 (sham) were not given any treatment after uveitis was induced. Rats in group 3 were given intraperitoneal infliximab 0.5 mg/100 mL on days 0, 1, 3, 5, and 7 following induction of uveitis on day 14 of the study. Rats in group 4 were given intraperitoneal ghrelin 10 ng/kg/day for 7 days following induction of uveitis. On day 21 of the study, enucleated globes were subjected to histopathologic examination. Vitreous levels of IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay. Results Vitreous levels of IL-1, IL-6, and TNF-α were significantly increased in the sham group relative to the control group (P < 0.05), but showed a significant decrease in the group treated with infliximab (P < 0.05). Cytokine levels also decreased in the ghrelin-treated group, but the decrease was not statistically significant (P > 0.05). Conclusion Ghrelin failed to decrease the IL-1, IL-6, and TNF-α levels that play a critical role in the pathogenesis of uveitis. PMID:23341733

  14. Viral posterior uveitis

    PubMed Central

    Lee, Joanne H.; Agarwal, Aniruddha; Mahendradas, Padmamalini; Lee, Cecilia S.; Gupta, Vishali; Pavesio, Carlos E.; Agrawal, Rupesh

    2017-01-01

    The causes of posterior uveitis can be divided into infectious, autoimmune, or masquerade syndromes. Viral infections, a significant cause of sight-threatening ocular diseases in the posterior segment, include human herpesviruses, measles, rubella, and arboviruses such as dengue, West Nile, and chikungunya virus. Viral posterior uveitis may occur as an isolated ocular disease in congenital or acquired infections or as part of a systemic viral illness. Many viruses remain latent in the infected host with a risk of reactivation that depends on various factors, including virulence and host immunity, age, and comorbidities. Although some viral illnesses are self-limiting and have a good visual prognosis, others, such as cytomegalovirus retinitis or acute retinal necrosis, may result in serious complications and profound vision loss. Since some of these infections may respond well to antiviral therapy, it is important to work up all cases of posterior uveitis to rule out an infectious etiology. We review the clinical features, diagnostic tools, treatment regimens, and long-term outcomes for each of these viral posterior uveitides. PMID:28012878

  15. [HLA-B27 Positive Acute Anterior Uveitis - A Translational Perspective].

    PubMed

    Heiligenhaus, Arnd; Kasper, Maren; Grajewski, Rafael

    2017-05-01

    Background HLA-B27 positive acute anterior uveitis is the most common type of uveitis, and it is an autoimmune disease that can be triggered by infections. The precise mechanism of the interaction between involved microbes (mostly gram negative bacteria) and the host immune system is not clear. The disease probably results from an imbalance between pro- and anti-inflammatory components. Project description This article gives a compact overview about the current knowledge of the clinic and the etiopathogenesis of acute anterior uveitis as a basis for future research approaches. The goal of the current research is to classify the cellular and molecular pathogenetic factors in acute anterior uveitis. In this regard, a project on uveitis within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye", examines the hypothesis that dysregulation of regulatory cell populations and anti-inflammatory cytokines, such as interleukin-10 (IL-10), might contribute to the development of ocular autoimmunity following infections. The goal is to establish new markers for individual susceptibility in the risk group of the HLA-B27 positive population, because only about 1% of the HLA-B27 positive population will eventually develop acute anterior uveitis. Conclusions Translational research approaches to identify predisposed risk groups from the HLA-B27 population could improve patient care both on a prophylactic and a therapeutic level. Georg Thieme Verlag KG Stuttgart · New York.

  16. [Pathophysiology and new treatment of uveitis].

    PubMed

    Yanai, Ryoji; Takeda, Atsunobu; Yoshimura, Takeru; Sonoda, Koh-Hei

    2014-01-01

    Uveitis is narrow-defined inflammation of the uvea, also clinically include all inflammatory conditions in the eye. Uveitis may occur as a consequence of various causes and background, such as autoimmune diseases, infections, and hematopoietic malignancy. We have to treat uveitis not only controlling the inflammation but also maintaining up the visual function of the eye because the most uveitis is chronic and relapsing inflammatory disorder. Behçét's disease is a systemic disease and results in loss of vision without adequate treatment. Behçét's disease was a representative of vision loss uveitis because Behçét's patient usually had treatment resistance of conventional treatment, such as colchicine and cyclosporine. However, biological therapy with TNF-α, which started from 2007, has revolutionized the treatment strategy of Behçét's disease. It is not too much to say that Behçét's patient is free from fear of vision loss by the dramatic decrease of ocular attach. Biological therapy is not approved as a treatment of uveitis except Behçét's disease. Some protracted cases of Sarcoidosis and Vogt-Koyanagi-Harada disease are resistant to corticosteroid therapy and require new treatment. In this review, we discuss the pathophysiology of uveitis and report new treatment of Behçét's disease by biological therapy.

  17. Uveitis associated with juvenile idiopathic arthritis.

    PubMed

    Sen, Ethan S; Dick, Andrew D; Ramanan, Athimalaipet V

    2015-06-01

    Uveitis is a potentially sight-threatening complication of juvenile idiopathic arthritis (JIA). JIA-associated uveitis is recognized to have an autoimmune aetiology characterized by activation of CD4(+) T cells, but the underlying mechanisms might overlap with those of autoinflammatory conditions involving activation of innate immunity. As no animal model recapitulates all the features of JIA-associated uveitis, questions remain regarding its pathogenesis. The most common form of JIA-associated uveitis is chronic anterior uveitis, which is usually asymptomatic initially. Effective screening is, therefore, essential to detect early disease and commence treatment before the development of visually disabling complications, such as cataracts, glaucoma, band keratopathy and cystoid macular oedema. Complications can result from uncontrolled intraocular inflammation as well as from its treatment, particularly prolonged use of high-dose topical corticosteroids. Accumulating evidence supports the early introduction of systemic immunosuppressive drugs, such as methotrexate, as steroid-sparing agents. Prospective randomized controlled trials of TNF inhibitors and other biologic therapies are underway or planned. Future research should aim to identify biomarkers to predict which children are at high risk of developing JIA-associated uveitis or have a poor prognosis. Such biomarkers could help to ensure that patients receive earlier interventions and more-potent therapy, with the ultimate aim of reducing loss of vision and ocular morbidity.

  18. Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

    PubMed

    Rao, Narsing A; Saraswathy, Sindhu; Pararajasegaram, Geeta; Bhat, Suraj P

    2012-01-01

    The small heat shock protein, αA-crystallin null (αA-/-) mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice), which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ), both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

  19. High Levels of Serum Ubiquitin and Proteasome in a Case of HLA-B27 Uveitis.

    PubMed

    Rossi, Settimio; Gesualdo, Carlo; Maisto, Rosa; Trotta, Maria Consiglia; Di Carluccio, Nadia; Brigida, Annalisa; Di Iorio, Valentina; Testa, Francesco; Simonelli, Francesca; D'Amico, Michele; Di Filippo, Clara

    2017-02-26

    In this paper, the authors describe a case of high serum levels of ubiquitin and proteasome in a woman under an acute attack of autoimmune uveitis. The woman was 52 years old, diagnosed as positive for the Human leukocyte antigen-B27 gene, and came to our observation in January 2013 claiming a severe uveitis attack that involved the right eye. During the acute attack of uveitis, this woman had normal serum biochemical parameters but higher levels of serum ubiquitin and proteasome 20S subunit, with respect to a healthy volunteer matched for age and sex. These levels correlated well with the clinical score attributed to uveitis. After the patient was admitted to therapy, she received oral prednisone in a de-escalation protocol (doses from 50 to 5 mg/day) for four weeks. Following this therapy, she had an expected reduction of clinical signs and score for uveitis, but concomitantly she had a reduction of the serum levels of ubiquitin, poliubiquitinated proteins (MAb-FK1) and proteasome 20S activity. Therefore, a role for ubiquitin and proteasome in the development of human autoimmune uveitis has been hypothesized.

  20. What causes relapses of autoimmune diseases? The etiological role of autoreactive T cells.

    PubMed

    Wildner, Gerhild; Kaufmann, Ulrike

    2013-09-01

    Most human autoimmune diseases have a relapsing-remitting or a chronic progressive course, while animal models are usually acute and monophasic. In our experimental animal model the disease can be either monophasic or remitting, depending on the autoantigen used for induction, and it appears to lie in the effector phenotype of the elicited T helper cell response. Since both, monophasic and relapsing courses of disease are induced by immunization as well as by adoptive transfer of peptide-specific, CD4(+) T cells, we were able to directly compare the transcriptomes of pathogenic T cell lines by gene array analysis and qPCR as well as protein expression. Upregulated genes were only determined in T cells inducing relapsing uveitis and belong to certain pathways of antigen presentation, activation, inflammation, migration and survival, comprising WNT, Hedgehog, MAP-kinase and JAK/STAT-pathways. These pathways are partially interacting with each other, and the central molecule upregulated in T cells causing relapsing disease was found to be IFN-γ. Here the course of the autoimmune diseases strictly depends on the characteristics of the autoreactive T cells, which are already determined at their early stage of antigen-specific activation. Our rat models of experimental autoimmune uveitis could help elucidating the immune mechanisms behind relapsing autoimmunity in order to develop better therapeutic strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Comparative Proteomic Analysis of Two Uveitis Models in Lewis Rats.

    PubMed

    Pepple, Kathryn L; Rotkis, Lauren; Wilson, Leslie; Sandt, Angela; Van Gelder, Russell N

    2015-12-01

    Inflammation generates changes in the protein constituents of the aqueous humor. Proteins that change in multiple models of uveitis may be good biomarkers of disease or targets for therapeutic intervention. The present study was conducted to identify differentially-expressed proteins in the inflamed aqueous humor. Two models of uveitis were induced in Lewis rats: experimental autoimmune uveitis (EAU) and primed mycobacterial uveitis (PMU). Differential gel electrophoresis was used to compare naïve and inflamed aqueous humor. Differentially-expressed proteins were separated by using 2-D gel electrophoresis and excised for identification with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Expression of select proteins was verified by Western blot analysis in both the aqueous and vitreous. The inflamed aqueous from both models demonstrated an increase in total protein concentration when compared to naïve aqueous. Calprotectin, a heterodimer of S100A8 and S100A9, was increased in the aqueous in both PMU and EAU. In the vitreous, S100A8 and S100A9 were preferentially elevated in PMU. Apolipoprotein E was elevated in the aqueous of both uveitis models but was preferentially elevated in EAU. Beta-B2-crystallin levels decreased in the aqueous and vitreous of EAU but not PMU. The proinflammatory molecules S100A8 and S100A9 were elevated in both models of uveitis but may play a more significant role in PMU than EAU. The neuroprotective protein β-B2-crystallin was found to decline in EAU. Therapies to modulate these proteins in vivo may be good targets in the treatment of ocular inflammation.

  2. Profile of adalimumab and its potential in the treatment of uveitis

    PubMed Central

    Balevic, Stephen J; Rabinovich, C Egla

    2016-01-01

    Uveitis refers to the presence of intraocular inflammation, and as a strict definition compromises the iris and ciliary body anteriorly and the choroid posteriorly (the uvea). Untreated, uveitis can lead to visual loss or blindness. The etiology of uveitis can include both infectious and noninfectious (usually immune-mediated) causes, the latter of which are often mediated predominantly by Th1 CD4+ T-cells that secrete proinflammatory cytokines. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of uveitis, which at high concentrations can cause excess inflammation and tissue damage. Adalimumab is a recombinant human IgG1 monoclonal antibody specific for human TNF-α. Historically, corticosteroids and methotrexate were used to treat uveitis; however, newer biologic agents such as adalimumab have revolutionized therapy for noninfectious uveitis. Adalimumab has shown efficacy in treating refractory uveitis in multiple settings, including idiopathic disease, juvenile idiopathic arthritis, sarcoidosis, Behçets disease, and uveitis secondary to spondyloarthropathies, among several other noninfectious uveitis conditions. In this paper, we will review the profile of adalimumab, the role of TNF-α in uveitis, discuss safety data, and summarize key articles evaluating the efficacy of adalimumab in treating uveitis secondary to the most commonly associated autoimmune diseases. PMID:27698552

  3. Profile of adalimumab and its potential in the treatment of uveitis.

    PubMed

    Balevic, Stephen J; Rabinovich, C Egla

    2016-01-01

    Uveitis refers to the presence of intraocular inflammation, and as a strict definition compromises the iris and ciliary body anteriorly and the choroid posteriorly (the uvea). Untreated, uveitis can lead to visual loss or blindness. The etiology of uveitis can include both infectious and noninfectious (usually immune-mediated) causes, the latter of which are often mediated predominantly by Th1 CD4 + T-cells that secrete proinflammatory cytokines. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of uveitis, which at high concentrations can cause excess inflammation and tissue damage. Adalimumab is a recombinant human IgG1 monoclonal antibody specific for human TNF-α. Historically, corticosteroids and methotrexate were used to treat uveitis; however, newer biologic agents such as adalimumab have revolutionized therapy for noninfectious uveitis. Adalimumab has shown efficacy in treating refractory uveitis in multiple settings, including idiopathic disease, juvenile idiopathic arthritis, sarcoidosis, Behçets disease, and uveitis secondary to spondyloarthropathies, among several other noninfectious uveitis conditions. In this paper, we will review the profile of adalimumab, the role of TNF-α in uveitis, discuss safety data, and summarize key articles evaluating the efficacy of adalimumab in treating uveitis secondary to the most commonly associated autoimmune diseases.

  4. A Review of the Course and Treatment of Non-Infectious Uveitis during Pregnancy.

    PubMed

    Grotting, Lindsay A; Papaliodis, George N

    2017-01-01

    Inflammatory conditions such as autoimmune uveitis often occur in women of childbearing age. During pregnancy, women may experience exacerbations of their disease in the first trimester. In the later stages of pregnancy, however, the uveitis tends to remain less active. The management of uveitis during pregnancy is a challenging task, forcing the physician to re-evaluate the patient's current therapy and offer alternative options that pose the least risk to the patient and fetus. This article will review treatments widely used for uveitis, including corticosteroid therapy, anti-metabolites, calcineurin inhibitors, and biologic therapy. It will evaluate the use of these medications in pregnancy and the postpartum state.

  5. A Low Concentration of Tacrolimus/Semifluorinated Alkane (SFA) Eyedrop Suppresses Intraocular Inflammation in Experimental Models of Uveitis.

    PubMed

    De Majumdar, S; Subinya, M; Korward, J; Pettigrew, A; Scherer, D; Xu, H

    2017-01-01

    Corticosteroids remain the mainstay therapy for uveitis, a major cause of blindness in the working age population. However, a substantial number of patients cannot benefit from the therapy due to steroids resistance or intolerance. Tacrolimus has been used to treat refractory uveitis through systemic administration. The aim of this study was to evaluate the therapeutic potential of 0.03% tacrolimus eyedrop in mouse models of uveitis. 0.03% tacrolimus in perfluorobutylpentane (F4H5) (0.03% Tacrolimus/SFA) was formulated using a previously published protocol. Tacrolimus suspended in PBS (0.03% Tacrolimus/PBS) was used as a control. In addition, 0.1% dexamethasone (0.1% DXM) was used as a standard therapy control. Endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) were induced in adult C57BL/6 mice using protocols described previously. Mice were treated with eyedrops three times/day immediately after EIU induction for 48 h or from day 14 to day 25 post-immunization (for EAU). Clinical and histological examinations were conducted at the end of the experiment. Pharmacokinetics study was conducted in mice with and without EIU. At different times after eyedrop treatment, ocular tissues were collected for tacrolimus measurement. The 0.03% Tacrolimus/SFA eyedrop treatment reduced the clinical scores and histological scores of intraocular inflammation in both EIU and EAU to the levels similar to 0.1% DXM eyedrop treatment. The 0.03% Tacrolimus/PBS did not show any suppressive effect in EIU and EAU. Pharmacokinetic studies showed that 15 min after topical administration of 0.03% Tacrolimus/SFA, low levels of tacrolimus were detected in the retina (48 ng/g tissue) and vitreous (2.5 ng/ml) in normal mouse eyes, and the levels were significantly higher in EIU eyes (102 ng/g tissue in the retina and 24 ng/ml in the vitreous). Tacrolimus remained detectable in intraocular tissues of EIU eyes 6 h after topical administration (68 ng/g retinal tissue, 10

  6. Comparative Proteomic Analysis of Two Uveitis Models in Lewis Rats

    PubMed Central

    Pepple, Kathryn L.; Rotkis, Lauren; Wilson, Leslie; Sandt, Angela; Van Gelder, Russell N.

    2015-01-01

    Purpose Inflammation generates changes in the protein constituents of the aqueous humor. Proteins that change in multiple models of uveitis may be good biomarkers of disease or targets for therapeutic intervention. The present study was conducted to identify differentially-expressed proteins in the inflamed aqueous humor. Methods Two models of uveitis were induced in Lewis rats: experimental autoimmune uveitis (EAU) and primed mycobacterial uveitis (PMU). Differential gel electrophoresis was used to compare naïve and inflamed aqueous humor. Differentially-expressed proteins were separated by using 2-D gel electrophoresis and excised for identification with matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF). Expression of select proteins was verified by Western blot analysis in both the aqueous and vitreous. Results The inflamed aqueous from both models demonstrated an increase in total protein concentration when compared to naïve aqueous. Calprotectin, a heterodimer of S100A8 and S100A9, was increased in the aqueous in both PMU and EAU. In the vitreous, S100A8 and S100A9 were preferentially elevated in PMU. Apolipoprotein E was elevated in the aqueous of both uveitis models but was preferentially elevated in EAU. Beta-B2–crystallin levels decreased in the aqueous and vitreous of EAU but not PMU. Conclusions The proinflammatory molecules S100A8 and S100A9 were elevated in both models of uveitis but may play a more significant role in PMU than EAU. The neuroprotective protein β-B2–crystallin was found to decline in EAU. Therapies to modulate these proteins in vivo may be good targets in the treatment of ocular inflammation. PMID:26747776

  7. Experimental arthritis and uveitis in rats associated with Mycobacterium butyricum.

    PubMed

    Petty, R E; Hunt, D W; Mathers, D M; McCormick, A Q; Barker, H; Southwood, T R; Corson, L

    1994-08-01

    To determine if the anterior uveitis associated with adjuvant arthritis (AA) in the rat can be passively transferred with arthritis to syngeneic recipients using spleen cells or T cell lines prepared from animals given complete Freund's adjuvant (CFA) and Mycobacterium butyricum (M. butyricum) in incomplete Freund's adjuvant (IFA). Spleen cells from Lewis or Lewis SsN rats given IFA, CFA, type I collagen in IFA (CI-IFA), or type II collagen in IFA (CII-IFA) were administered to naive rats or rats treated with pertussis toxin or bacterial endotoxin. Three CD4+ T cell lines, propagated from CFA injected rats and maintained in vitro with M. butyricum (M-1), bovine proteoglycan (PR-1) or an extract of M. butyricum (MBE-1) were administered to naive or immunosuppressed rats. The arthritogenic and uveitogenic properties of these cell preparations and intradermal MBE-IFA, CII-IFA and intraperitoneal (ip) M. butyricum without adjuvant were evaluated. Uveitis was observed in 15/69 (22%) arthritic rats given CFA. Spleen cells prepared from CFA injected rats caused arthritis in 55 (82%) and uveitis in 2 (3%) of 67 cell recipients. Uveitis occurred in 2/6 cell recipients pretreated with bacterial endotoxin. Neither uveitis nor arthritis was observed in rats given IFA (0/6) or spleen cells prepared from rats given IFA (0/27), CI-IFA (0/6), or CII-IFA (0/28). CII-IFA produced polyarthritis in 5/6 rats, but no uveitis. CII-IFA induced arthritis associated uveitis in 1/15 animals receiving spleen cells from rats given CII-IFA, but not those given CI-IFA (0/3) or IFA (0/13). Uveitis was observed in one recipient of the M-1 T cell line and in 2 recipients of the PR-1 T cell line. Immunization with 400 micrograms of MBE-IFA induced uveitis but not arthritis in 3/11 animals. The MBE specific T cell line was neither arthritogenic nor uveitogenic. A high frequency (5/6) of uveitis accompanied arthritis in male Lewis rats given ip M. butyricum. Arthritis occurred in 4/10 female Lewis

  8. Characterization of cytokines associated with Th17 cells in the eyes of horses with recurrent uveitis.

    PubMed

    Regan, Daniel P; Aarnio, Megan C; Davis, Wesley S; Carmichael, K Paige; Vandenplas, Michel L; Lauderdale, James D; Moore, Phillip A

    2012-05-01

    Equine recurrent uveitis (ERU) is a spontaneous disease that is the most common cause of blindness in horses, affecting up to 15% of the horse population. Th17 cells are a major cell population driving the pathogenesis in several mouse models of autoimmune inflammation, including experimental autoimmune uveitis. The purpose of this study is to investigate the role a Th17 cell-mediated response plays in the pathogenesis of ERU. Banked, Davidson's-fixed equine globes histopathologically diagnosed with ERU (n = 7) were compared immunohistochemically with healthy control globes (n = 7). Immunohistochemical staining was performed using a pan-Leptospira antibody and antibodies against IL-6, IL-17, and IL-23. Additionally, immunostaining was performed for T-cell (CD3) and B-cell (CD79α) markers. Specificity of immunoreactivity was confirmed by western blot analysis. Immunohistochemical staining was positive for IL-6, IL-17, and IL-23 within the cytoplasm of nonpigmented ciliary epithelial cells and mononuclear inflammatory cells infiltrating the iris, and ciliary body of ERU horses (n = 7) but negative in controls (n = 7). ERU-affected eyes were CD3 positive (n = 7) and CD79α negative (n = 7). Staining for Leptospira was negative in all ERU and control globes. Strong immunoreactivity for IL-6, IL-17, and IL-23, in conjunction with the fact that T lymphocytes are the predominating inflammatory cells present in ERU, suggests that IL-17-secreting helper T-cells play a role in the pathogenesis of ERU. These findings suggest that horses with ERU may serve as a naturally occurring animal model for autoimmune uveitis. © 2011 American College of Veterinary Ophthalmologists.

  9. Platelet-Activating Factor (PAF) Receptor Antagonism Modulates Inflammatory Signaling in Experimental Uveitis.

    PubMed

    Elison, Jasmine R; Weinstein, Jessica E; Sheets, Kristopher G; Regan, Cornelius E; Lentz, Jennifer J; Reinoso, Maria; Gordon, William C; Bazan, Nicolas G

    2018-04-11

    The phospholipid mediator platelet-activating factor (PAF) activates an inflammatory response that includes arachidonic acid release and prostaglandin production in the eye, increasing vascular permeability and inflammation. The purpose of this study is to investigate the action of LAU-0901, a novel PAF receptor antagonist, on experimental uveitis. Uveitis was induced in Lewis rats by lipopolysaccharide treatment. LAU-0901 was then delivered systemically in different concentrations at plus 4 and 16 hours, or vehicle injected as controls. Additional animals were used for histological analyses of untreated, uveitis, and uveitis-plus-LAU-0901 retinas. Conventional histological and immunohistochemical methods were employed. A slit lamp and Spectral Domain-Ocular Coherence Tomography (SD-OCT) retinal imager was used for anterior segment photography and posterior pole OCT. Rats were euthanized 4 hours after the second LAU-0901 injection in this 24-hour model. Aqueous humor was collected and quantified, and also analyzed for tumor necrosis factor alpha (TNF-α). Uveitic eyes demonstrated hypopyon formation, leukocyte infiltration, and an increase in aqueous protein and TNF-α levels. LAU-0901 treatment resulted in a dose-dependent reduction in inflammation, reflected by reduced total protein levels (up to a 64% reduction). Moreover, hypopyon was prevented, leukocytes were absent in vitreous and aqueous humor, and TNF-α levels were reduced by 91%. The PAF receptor antagonist LAU-0901 decreases ocular inflammation in a rat model of anterior uveitis in a dose-dependent manner, suggesting that use of this molecule may provide a means to attenuate inflammation onset and offer a future alternative or adjunctive treatment for ocular inflammation.

  10. Emerging role of IL-35 in inflammatory autoimmune diseases.

    PubMed

    Su, Lin-Chong; Liu, Xiao-Yan; Huang, An-Fang; Xu, Wang-Dong

    2018-05-03

    Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis. In addition, functional analysis suggested that IL-35 is critical in the onset and development of these diseases. Therefore, the present study will systematically review what had been occurred regarding IL-35 in inflammatory autoimmune disease. The information collected will help to understand the biologic role of IL-35 in immune cells, and give information about the therapeutic potential of IL-35 in these diseases. Copyright © 2018. Published by Elsevier B.V.

  11. Interleukin-35 induces regulatory B cells that suppress autoimmune disease.

    PubMed

    Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M; Mahdi, Rashid M; Dolinska, Monika B; Sergeev, Yuri V; Wingfield, Paul T; Kim, Sung-Hye; Egwuagu, Charles E

    2014-06-01

    Interleukin-10 (IL-10)-producing regulatory B (Breg) cells suppress autoimmune disease, and increased numbers of Breg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4(+) T cells to regulatory T (Treg) cells. The mechanisms mediating the induction and development of Breg cells remain unclear. Here we show that IL-35 induces Breg cells and promotes their conversion to a Breg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12Rβ2 KO mice) produced less Breg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of Breg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (TH17) and TH1 cells while promoting Treg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12Rβ2 and IL-27Rα subunits. As IL-35 also induced the conversion of human B cells into Breg cells, these findings suggest that IL-35 may be used to induce autologous Breg and IL-35(+) Breg cells and treat autoimmune and inflammatory disease.

  12. A Glimpse into Uveitis in the Aging Eye: Pathophysiology, Clinical Presentation and Treatment Considerations.

    PubMed

    Akinsoji, Elizabeth; Goldhardt, Raquel; Galor, Anat

    2018-05-01

    Uveitis describes a group of inflammatory conditions of the eye that have various underlying causes and clinical presentations. Susceptibilities to uveitis in the elderly may be attributed to age-related risk factors such as immunosenescence, increased immunological inflammatory mediators, and autoimmunity. Overall, anterior uveitis is more common than posterior and panuveitis in the general population and also in the elderly. Some causes of uveitis in the elderly are herpes simplex virus, ocular ischemic syndrome, sarcoidosis, and central nervous system lymphoma, and these will be discussed in detail herein. Eye care professionals need to consider the wide differential for uveitis, obtain the appropriate history, conduct a detailed clinical examination, and tailor management to the clinical presentation and underlying cause of disease. The challenges of polypharmacy and nonadherence in the elderly impact patient outcomes and must be taken into consideration when considering treatment.

  13. Retinal Mueller glial cells trigger the hallmark inflammatory process in autoimmune uveitis.

    PubMed

    Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Gerhards, Hartmut; Ueffing, Marius; Deeg, Cornelia A

    2007-06-01

    Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease severity. Additionally, uveitic changes in the retina were accompanied by upregulation of aldose 1-epimerase, selenium-binding protein 1, alpha crystallin A chain, phosphatase 2A inhibitor (SET), and glial fibrillary acidic protein (GFAP), the latter indicating an involvement of retinal Mueller glial cells (RMG) in disease process. To confirm this, we screened for additional RMG-specific markers and could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin and GFAP and downregulate glutamine synthetase. These expression patterns suggest for an activated state of RMG, which further downregulate the expression of pigment epithelium-derived factor (PEDF) and begin expressing interferon-gamma, a pro-inflammatory cytokine typical for T-helper 1 cells. We thus propose that RMG may play a fatal role in uveitic disease progression by directly triggering inflammatory processes through the expression and secretion of interferon-gamma.

  14. The Use of Biologic Therapies in Uveitis.

    PubMed

    Schwartzman, Sergio; Schwartzman, Monica

    2015-12-01

    Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective

  15. A proteomic approach for studying the pathogenesis of spontaneous equine recurrent uveitis (ERU).

    PubMed

    Deeg, Cornelia A

    2009-03-15

    Equine recurrent uveitis (ERU) is a wide spread disease of the eye, which is the main cause for blindness in horses worldwide. Meanwhile, ERU is also accepted as the only reliable spontaneous model for human autoimmune uveitis. We identified and characterized novel autoantigens by analyzing the autoantibody-binding pattern from ERU cases to the retinal proteome. Cellular retinaldehyde-binding protein (CRALBP) and malate dehydrogenase (MDH) were detected as novel ERU autoantigens by this approach. B- and T-cell autoreactivity was detected to both autoantigens in ERU cases. The evaluation of the pathological relevance of CRALBP and MDH brought surprising results. While CRALBP-induced uveitis with high incidence in rats and horses, MDH was only uveitogenic in Lewis rats, but not in the horse itself.

  16. Kininogen in autoimmune uveitis: decrease in peripheral blood stream versus increase in target tissue.

    PubMed

    Zipplies, Johanna K; Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; van der Meijden, Christiaan H; Stangassinger, Manfred; Ueffing, Marius; Deeg, Cornelia A

    2010-01-01

    Equine recurrent uveitis (ERU) is an incurable disease affecting the inner eye that leads to blindness, through activated T cells that pass the blood-retinal barrier and destroy the retina. Serum markers are a desirable choice for monitoring development of disease, as serum is easy accessible and the markers could serve to predict the beginning of disease or an imminent relapse. In this study, serum proteomes (depleted of high-abundance serum proteins) of horses with ERU and healthy controls were compared with the 2-D DIGE (two-dimensional gel electrophoresis) technique to identify differentially expressed proteins. The expression pattern of a candidate protein in retina and vitreous was validated by Western blots and immunohistochemistry. Ten differentially expressed proteins could be identified by mass spectrometry (MALDI-TOF/TOF). Five proteins--IgM, IgG4 hc, serotransferrin, alpha-2HS-glycoprotein, and complement factor B--were upregulated in the uveitic state, whereas the five proteins albumin, apolipoprotein A-IV and H, IgG5 hc, and high-molecular-weight kininogen (HK) showed a significantly lower expression in sera of uveitis cases. Of interest, kininogen was significantly upregulated in the target tissues vitreous and retina. HK is a plasma protein with multiple physiological functions, with an important role in inflammation and promoting neovascularization. Most interesting is the as of yet unaddressed association of HK with uveitis. Immunohistochemistry showed coexpression of kininogen and VEGF in inflamed eyes. Since neovascularization plays a major role in the pathogenesis of uveitis, the identification of a proangiogenic factor in the retina presents an important finding and may contribute to elucidating the pathogenesis of uveitis.

  17. Changes in patterns of uveitis at a tertiary referral center in Northern Italy: analysis of 990 consecutive cases.

    PubMed

    Luca, Cimino; Raffaella, Aldigeri; Sylvia, Marchi; Valentina, Mastrofilippo; Fabiana, Viscogliosi; Marco, Coassin; Annamaria, Soldani; Luisa, Savoldi; Alessandro, De Fanti; Lucia, Belloni; Alessandro, Zerbini; Maria, Parmeggiani; Matthew, Chersich; Alessandra, Soriano; Carlo, Salvarani; Luigi, Fontana

    2018-02-01

    The role of uveitis, an uncommon ocular disease, is often neglected in research and treatment of autoimmune conditions. The study described the spectrum of uveitis at a referral center in North Italy, and compared that to a previously published series of patients. We reviewed all patients with uveitis diagnosed from 2013 to 2015 at the Immunology Eye Unit, Arcispedale S. M. Nuova-IRCCS, Reggio Emilia, Italy. We examined patient characteristics, disease spectrum, and etiologies. In total, 990 cases of uveitis were identified, who were mostly female (59%) with a median age at presentation of 44 years (interquartile range = 29-57). Anterior uveitis was most frequent (53.5%), followed by panuveitis (22.8%), posterior (16.2%), and intermediate uveitis (5.5%). Anterior herpetic uveitis (15.6%), Fuchs uveitis (9.7%), and HLA-B27 positive anterior uveitis (7.7%) were the most common specific diagnoses. Compared with the previous series, we observed an increased incidence of uveitis, and a different pattern of diagnoses. Rates of herpetic, HLA-B27 positive uveitis, and presumed ocular tuberculosis were higher, but Fuchs uveitis was less frequent. The pattern of uveitis appears to be changing, very likely due to population-level increases in infectious diseases, to the availability of new diagnostic tests and to the interdisciplinary approach used in patient diagnosis.

  18. Complement factor B expression profile in a spontaneous uveitis model.

    PubMed

    Zipplies, Johanna K; Kirschfink, Michael; Amann, Barbara; Hauck, Stefanie M; Stangassinger, Manfred; Deeg, Cornelia A

    2010-12-01

    Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

  19. SUPPRESSION OF ALLERGIC UVEITIS BY 6-MERCAPTOPURINE

    PubMed Central

    Wirostko, E.; Halbert, S. P.

    1962-01-01

    Experimental uveitis in rabbits was induced by single intraocular antigen injection. Treatment with 6-MP for 14 days suppressed the allergic inflammation and antibody response. A good correlation was demonstrated between the degree of uveitis and the antibody titer. PMID:14001284

  20. Emerging Drugs for Uveitis

    PubMed Central

    Larson, Theresa; Nussenblatt, Robert B.; Sen, H. Nida

    2010-01-01

    Importance of the Field Uveitis is a challenging disease covering both infectious and noninfectious conditions. The current treatment strategies are hampered by the paucity of randomized controlled trials (RCTs) and few trials comparing efficacy of different agents. Areas Covered in this Review This review describes the current and future treatments of uveitis. A literature search was performed in PUBMED from 1965 to 2010 on drugs treating ocular inflammation with emphasis placed on more recent, larger studies. What the Reader Will Gain Readers should gain a basic understanding of current treatment strategies beginning with corticosteroids and transitioning to steroid sparing agents. Steroid sparing agents include the antimetabolites which include methotrexate, azathioprine, and mycophenolate mofetil; the calcineurin inhibitors which include cyclosporine, tacrolimus; alkylating agents which include cyclophosphamide and chlorambucil; and biologics which include the TNF-α inhibitors infliximab, adalimumab, and etanercept; daclizumab, interferon α2a, and rituximab. Take Home Message Newer agents are typically formulated from existing drugs or developed based on new advances in immunology. Future treatment will require a better understanding of the mechanisms involved in autoimmune diseases and better delivery systems in order to provide targeted treatment with minimal side effects. PMID:21210752

  1. Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course?

    PubMed

    Jouve, Léa; Benrabah, Rabah; Héron, Emmanuel; Bodaghi, Bahram; Le Hoang, Phuc; Touitou, Valérie

    2017-06-01

    Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (p<0.05), with a tendency toward a higher rate of chronic uveitis (p = 0.06). MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.

  2. The Role of Gender in Uveitis and Ocular Inflammation

    PubMed Central

    Yeung, Ian YL; Popp, Nicholas A; Chan, Chi-Chao

    2015-01-01

    Uveitides can be due to non-infectious and infectious etiologies. It has been observed that there is a gender difference with a greater preponderance of non-infectious uveitis in women than in men. This review will describe both non-infectious and infectious uveitides and describes some of the current autoimmune mechanisms thought to be underlying the gender difference. It will specifically look at non-infectious uveitides with systemic involvement including juvenile idiopathic arthritis, spondyloarthopathies, sarcoidosis, Behçet’s disease, and Vogt-Koyanagi-Harada disease and at uveitides without systemic involvement including sympathetic ophthalmia, birdshot chorioretinitis, and the white dot syndromes. Infectious uveitides like acute retinal necrosis, progressive outer retinal necrosis, and cytomegalovirus mediated uveitis will be mentioned. Different uveitides with female- or male- predominance are presented and discussed. PMID:26035764

  3. Uveitis- a rare disease often associated with systemic diseases and infections- a systematic review of 2619 patients

    PubMed Central

    2012-01-01

    Background Uveitis is an autoimmune disease of the eye that refers to any of a number of intraocular inflammatory conditions. Because it is a rare disease, uveitis is often overlooked, and the possible associations between uveitis and extra-ocular disease manifestations are not well known. The aim of this study was to characterize uveitis in a large sample of patients and to evaluate the relationship between uveitis and systemic diseases. Methods The present study is a cross-sectional study of a cohort of patients with uveitis. Records from consecutive uveitis patients who were seen by the Uveitis Service in the Department of Ophthalmology at the Medical University of Vienna between 1995 and 2009 were selected from the clinical databases. The cases were classified according to the Standardization of Uveitis Nomenclature Study Group criteria for Uveitis. Results Data were available for 2619 patients, of whom 59.9% suffered from anterior, 14.8% from intermediate, 18.3% from posterior and 7.0% from panuveitis. 37.2% of all cases showed an association between uveitis and extra-organ diseases; diseases with primarily arthritic manifestations were seen in 10.1% of all cases, non-infectious systemic diseases (i.e., Behçet´s disease, sarcoidosis or multiple sclerosis) in 8.4% and infectious uveitis in 18.7%. 49.4% of subjects suffering from anterior uveitis tested positively for the HLA-B27 antigen. In posterior uveitis cases 29% were caused by ocular toxoplasmosis and 17.7% by multifocal choroiditis. Conclusion Ophthalmologists, rheumatologists, infectiologists, neurologists and general practitioners should be familiar with the differential diagnosis of uveitis. A better interdisciplinary approach could help in tailoring of the work-up, earlier diagnosis of co-existing diseases and management of uveitis patients. PMID:22932001

  4. Noninvasive Ocular Drug Delivery System of Dexamethasone Sodium Phosphate in the Treatment of Experimental Uveitis Rabbit.

    PubMed

    Papangkorn, Kongnara; Prendergast, Eri; Higuchi, John W; Brar, Balbir; Higuchi, William I

    2017-12-01

    To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis. Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency. Efficacy and safety of DSP-Visulex were evaluated by ophthalmic observations and histopathological examinations for ocular inflammations and pathology. The control group exhibited panuveitis with significant inflammation in the vitreous, choroid, and retina, but less in the conjunctiva, cornea, and anterior chamber. The uveitis occurred within 24 h after induction and persisted throughout the study in the control group. All treatments showed some reduction in inflammation in the vitreous, choroid, and retina. The higher dose regimens generally showed more rapid and higher degree of resolution than the lower dose regimens. The posterior eye tissues of the 15% and 8% DSP-Visulex appeared normal with minimal or no inflammation, whereas the untreated eye and the 4% DSP-Visulex eyes showed minimal response. All DSP-Visulex regimens suppressed the signs of inflammation and were well tolerated over the course of a 29-day study. The 8% and 15% DSP-Visulex treatment regimens were safe and efficacious for anterior, intermediate, and posterior uveitis. On the other hand, the 4% DSP-Visulex regimen may only be considered for anterior and intermediate uveitis.

  5. Antigen-specific tolerance inhibits autoimmune uveitis in pre-sensitized animals by deletion and CD4+CD25+ T-regulatory cells.

    PubMed

    Matta, Bharati; Jha, Purushottam; Bora, Puran S; Bora, Nalini S

    2010-02-01

    The objective of this study was to inhibit experimental autoimmune anterior uveitis (EAAU) by establishing antigen-specific immune tolerance in animals pre-sensitized with melanin-associated antigen (MAA). Intravenous administration of MAA on days 6, 7, 8 and 9 post-immunization induced tolerance and inhibited EAAU in all Lewis rats. The number of cells (total T cells, CD4(+) T cells and CD8(+) T cells) undergoing apoptosis dramatically increased in the popliteal lymph nodes (LNs) of the tolerized animals compared with non-tolerized animals. In addition, Fas ligand (FasL), TNF receptor 1 (TNFR1) and caspase-8 were upregulated in tolerized rats. Proliferation of total lymphocytes, CD4(+)T cells and CD8(+) T cells (harvested from the popliteal LNs) in response to antigenic stimulation was drastically reduced in the state of tolerance compared with the cells from non-tolerized animals. The level of interferon (IFN)-gamma and IL-2 decreased, whereas TGF-beta2 was elevated in the state of tolerance. Furthermore, the number of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) increased in the popliteal LNs of tolerized animals compared with non-tolerized animals. In conclusion, our results suggest that deletion of antigen-specific T cells by apoptosis and active suppression mediated by Tregs has an important role in the induction of antigen specific immune tolerance in animals with an established immune response against MAA.

  6. Immune responses to retinal autoantigens and peptides in equine recurrent uveitis.

    PubMed

    Deeg, C A; Kaspers, B; Gerhards, H; Thurau, S R; Wollanke, B; Wildner, G

    2001-02-01

    To test the hypothesis that autoimmune mechanisms are involved in horses in which equine recurrent uveitis (ERU) develops spontaneously. Material obtained from horses treated for spontaneous disease by therapeutic routine vitrectomy was analyzed for total IgG content and IgG specific for S-Antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). The cellular infiltrate of the vitreous was analyzed by differential counts of cytospin preparations and flow cytometry using equine lymphocyte-specific antibodies. Antigen-specific proliferation assays were performed comparing peripheral blood lymphocytes (PBLs) with vitreal lymphocytes by stimulation with S-Ag and several S-Ag- and IRBP-derived peptides. The total IgG content of specimens from horses with ERU was very high with great variability among the investigated samples (11.5 +/- 8.0 mg). Autoantibodies to S-Ag or IRBP or both were found in 72% of vitreous specimens from horses with uveitis. The leukocyte infiltrates (up to 2 x 10(8) cells per sample) were dominated by lymphocytes (>90%) in most cases (22/32). Flow cytometry showed that more than 50% of these cells were CD4(+) T cells. In vitro stimulation of vitreal lymphocytes, but not of PBL, showed a strong proliferative response to peptides derived from S-Ag or IRBP in 9 of 12 patients. In the eyes of horses with ERU, IgG antibodies and autoreactive T cells specific for retinal antigens were detected. These results strongly support the hypothesis that ERU is an autoimmune-mediated disease and is highly similar to recurrent uveitis in humans in both clinical and immunologic parameters.

  7. [New etiological concepts in uveitis].

    PubMed

    Bodaghi, B

    2005-05-01

    Uveitis remains an important cause of visual impairment, particularly in young patients. Idiopathic forms of intraocular inflammation should no longer be regarded as a presumed clinical entity, and the ophthalmologist must reconsider the specific etiology of primary uveitis when the clinical examination does not yield a definitive diagnosis or when the course of the disease on corticosteroids remains atypical. Laboratory tests based on serum analysis have limited value and should not be considered as diagnostic proof in different clinical presentations. The diagnostic management of infectious uveitis has been greatly improved by the use of molecular techniques applied to ocular fluids and tissues. Polymerase chain reaction (PCR) technology is a powerful tool that should be proposed in atypical cases of uveitis or retinitis of unclear but potentially infectious origin. This strategy is a major step before using unconventional and new immunomodulatory agents such as anti-TNF-alpha molecules. Under strict experimental conditions including adequate testing to rule out a possible contamination, PCR and its variants have changed our practical approach to intraocular inflammatory disorders and have provided new details for the understanding of infectious uveitis. The concept of pathogen-induced intraocular inflammation can be revisited in the light of molecular data obtained after anterior chamber paracentesis or diagnostic vitrectomy.

  8. Pediatric Uveitis.

    PubMed

    Chan, Nicole Shu-Wen; Choi, Jessy; Cheung, Chui Ming Gemmy

    2018-01-01

    Pediatric uveitis differs from adult-onset uveitis and is a topic of special interest because of its diagnostic and therapeutic challenges. Children with uveitis are often asymptomatic and the uveitis is often chronic, persistent, recurrent, and resistant to conventional treatment. Anterior uveitis is the most common type of uveitis in children; the prevalence of intermediate, posterior, and panuveitis varies geographically and among ethnic groups. Regarding etiology, most cases of pediatric uveitis are idiopathic but can be due to systemic inflammatory disorders, infections, or a manifestation of masquerade syndrome. Ocular complications include cataracts, hypotony or glaucoma, band keratopathy, synechiae formation, macular edema, optic disc edema, choroidal neovascular membranes, and retinal detachment. These complications are often severe, leading to irreversible structural damage and significant visual disability due to delayed presentation and diagnosis, persistent chronic inflammation from suboptimal treatment, topical and systemic corticosteroid dependence, and delayed initiation of systemic disease‒modifying agents. Treatment for noninfectious uveitis is a stepwise approach starting with corticosteroids. Immunomodulatory therapy should be initiated in cases where quiescence cannot be achieved without steroid dependence. Patients should be monitored regularly for complications of uveitis along with systemic and ocular adverse effects from treatments. The goals are to achieve steroid-free durable remission, to reduce the risk of sight-threatening complications from the uncontrolled ocular inflammation, and to avoid the impact of lifelong burden of visual loss on the child and their family. Multidisciplinary management will ensure holistic care of affected children and improve the support for their families. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

  9. Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis.

    PubMed

    Wu, Wei; Zhang, Zhaoliang; Xiong, Taotao; Zhao, Wenguang; Jiang, Rou; Chen, Hao; Li, Xingyi

    2017-10-01

    Supramolecular hydrogels formed by the self-assembly of therapeutic agents have received considerable attention due to their high drug payload and carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination with Dex and calcium ion (Ca 2+ ) and further demonstrated its therapeutic efficacy in the control of ocular inflammation. The developed supramolecular hydrogel was thoroughly characterized by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked influence on the sol-gel transition behaviour of hydrogel and the proposed Dex supramolecular hydrogel displayed thixotropic properties. The drug release rate from Dex supramolecular hydrogel was dependent on the Ca 2+ concentration. In comparison with Dex aqueous solution, single intravitreal injections of Dex supramolecular hydrogel up to 30μg/eye were well tolerated without causing undesirable complications of fundus blood vessel tortuosity and lens opacity, as indicated by electroretinograms (ERGs), fundus photography and histopathology. Moreover, the administration by Dex supramolecular hydrogel exhibited a comparable anti-inflammatory efficacy to native Dex solution on an experimental autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the therapeutic efficacy had in a dosage-dependent manner. Histological observation and cytokines measurements indicated that both Dex solution and Dex supramolecular hydrogel (30μg/eye) treatment could significantly attenuate the inflammatory response in both anterior and posterior chambers via the downregulation of Th1 and Th17 effector responses. All these data suggested that the developed Dex supramolecular hydrogel might be a therapeutic alternative for non-infectious uveitis with minimal risk of the induction of lens opacity and fundus blood vessel tortuosity. A facile ionic cross-linking strategy was exploited to construct a dexamethasone sodium phosphate (Dex

  10. Therapeutic Potential of Shark Anti-ICOSL VNAR Domains is Exemplified in a Murine Model of Autoimmune Non-Infectious Uveitis.

    PubMed

    Kovaleva, Marina; Johnson, Katherine; Steven, John; Barelle, Caroline J; Porter, Andrew

    2017-01-01

    Induced costimulatory ligand (ICOSL) plays an important role in the activation of T cells through its interaction with the inducible costimulator, ICOS. Suppression of full T cell activation can be achieved by blocking this interaction and has been shown to be an effective means of ameliorating disease in models of autoimmunity and inflammation. In this study, we demonstrated the ability of a novel class of anti-ICOSL antigen-binding single domains derived from sharks (VNARs) to effectively reduce inflammation in a murine model of non-infectious uveitis. In initial selections, specific VNARs that recognized human ICOSL were isolated from an immunized nurse shark phage display library and lead domains were identified following their performance in a series of antigen selectivity and in vitro bioassay screens. High potency in cell-based blocking assays suggested their potential as novel binders suitable for further therapeutic development. To test this hypothesis, surrogate anti-mouse ICOSL VNAR domains were isolated from the same phage display library and the lead VNAR clone selected via screening in binding and ICOS/ICOSL blocking experiments. The VNAR domain with the highest potency in cell-based blocking of ICOS/ICOSL interaction was fused to the Fc portion of human IgG1 and was tested in vivo in a mouse model of interphotoreceptor retinoid-binding protein-induced uveitis. The anti-mICOSL VNAR Fc, injected systemically, resulted in a marked reduction of inflammation in treated mice when compared with untreated control animals. This approach inhibited disease progression to an equivalent extent to that seen for the positive corticosteroid control, cyclosporin A, reducing both clinical and histopathological scores. These results represent the first demonstration of efficacy of a VNAR binding domain in a relevant clinical model of disease and highlight the potential of VNARs for the treatment of auto-inflammatory conditions.

  11. Infectious Uveitis

    PubMed Central

    2015-01-01

    Infectious uveitis is one of the most common and visually devastating causes of uveitis in the US and worldwide. This review provides a summary of the identification, treatment, and complications associated with certain forms of viral, bacterial, fungal, helminthic, and parasitic uveitis. In particular, this article reviews the literature on identification and treatment of acute retinal necrosis due to herpes simplex virus, varicella virus, and cytomegalovirus. While no agreed-upon treatment has been identified, the characteristics of Ebola virus panuveitis is also reviewed. In addition, forms of parasitic infection such as Toxoplasmosis and Toxocariasis are summarized, as well as spirochetal uveitis. Syphilitic retinitis is reviewed given its increase in prevalence over the last decade. The importance of early identification and treatment of infectious uveitis is emphasized. Early identification can be achieved with a combination of maintaining a high suspicion, recognizing certain clinical features, utilizing multi-modal imaging, and obtaining specimens for molecular diagnostic testing. PMID:26618074

  12. A review and update on orphan drugs for the treatment of noninfectious uveitis

    PubMed Central

    You, Caiyun; Sahawneh, Haitham F; Ma, Lina; Kubaisi, Buraa; Schmidt, Alexander; Foster, C Stephen

    2017-01-01

    Introduction Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as “orphan drugs” and are widely used for systemic autoimmune diseases or organ transplantation. Area covered The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an “orphan drug for treating uveitis” by the US Food and Drug Administration (FDA). Our perspective IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for “on-label” use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease. PMID:28203051

  13. [Therapy of intermediate uveitis].

    PubMed

    Doycheva, D; Deuter, C; Zierhut, M

    2014-12-01

    Intermediate uveitis is a form of intraocular inflammation in which the vitreous body is the major site of inflammation. Intermediate uveitis is primarily treated medicinally and systemic corticosteroids are the mainstay of therapy. When recurrence of uveitis or side effects occur during corticosteroid therapy an immunosuppressive treatment is required. Cyclosporine A is the only immunosuppressive agent that is approved for therapy of uveitis in Germany; however, other immunosuppressive drugs have also been shown to be effective and well-tolerated in patients with intermediate uveitis. In severe therapy-refractory cases when conventional immunosuppressive therapy has failed, biologics can be used. In patients with unilateral uveitis or when the systemic therapy is contraindicated because of side effects, an intravitreal steroid treatment can be carried out. In certain cases a vitrectomy may be used.

  14. Presentation of suspected pediatric uveitis.

    PubMed

    Saeed, Muhammad Usman; Raza, Syed Hamid; Goyal, Sudeshna; Cleary, Gavin; Newman, William David; Chandna, Arvind

    2014-01-01

    Presentation of suspected pediatric uveitis: Pediatric uveitis is usually managed in specialized ophthalmic centers in the UK. Meaningful data acquisition in these clinics may be helpful in clinical governance, and healthcare planning in a specialty that is gradually changing due to changes in treatment choices. Retrospective analysis of prospectively acquired data in the Liverpool pediatric uveitis database was performed. Analysis of our data, based on 147 patients, with a mean age of 10 years, indicated a female to male ratio of 2:1. 99% of patients were Caucasian. Our data indicates 86% of all patients attending the uveitis clinic were diagnosed with juvenile idiopathic arthritis, followed by intermediate uveitis 5% and idiopathic uveitis 4%. 46% of patients required treatment. Systemic treatment included methotrexate (34%), prednisolone (14%), etanercept (6%), ciclosporin (6%), mycophenolate (3%), and infliximab (1%). Severe visual loss (defined by counting fingers or below vision) was seen in 10 eyes despite appropriately treated chronic uveitis. Our data shows uveitis-related ocular morbidity in a predominantly pediatric Caucasian population. Patients with severe and chronic uveitis may experience significant uveitis-related complications and subsequent visual loss despite aggressive treatment.

  15. Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

    PubMed

    Swadzba, Margarete E; Hauck, Stefanie M; Naim, Hassan Y; Amann, Barbara; Deeg, Cornelia A

    2012-01-01

    Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology.

  16. Curcumin and autoimmune disease.

    PubMed

    Bright, John J

    2007-01-01

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

  17. Uveitis in Spondyloarthritis: An Overview.

    PubMed

    Cantini, Fabrizio; Nannini, Carlotta; Cassarà, Emanuele; Kaloudi, Olga; Niccoli, Laura

    2015-11-01

    Autoimmune anterior uveitis (AU) accounts for at least half of the cases of noninfectious uveitis, and similarly to spondyloarthritis (SpA), its occurrence is related to HLA-B27 positivity. AU is significantly more frequently found in HLA-B27-positive subjects with SpA and is characterized by unilateral eye involvement, marked tendency to recur with involvement of both eyes in alternate fashion, and has good prognosis in the majority of cases. The estimated frequency of SpA in patients with AU is around 50%, whereas AU in SpA has been reported in at least 30% of cases. Across the SpA disease spectrum, AU has a frequency peak of 33.4% in patients with ankylosing spondylitis, while the estimated prevalence in psoriatic arthritis (PsA) and inflammatory bowel disease-associated SpA is 2%-25%, and 25%, respectively. In early PsA, the frequency of AU has been found in 9% of patients. The wide range of prevalence reported in PsA may be explained by the variable sets of classification criteria used for patient selection and the different length of followup. AU may precede the clinical features of SpA, may be present at diagnosis, or may complicate the SpA clinical course. However, the occurrence of AU in SpA as well as AU flares has been reduced through treatment of SpA with anti-tumor necrosis factor-α agents.

  18. Uveitis in children.

    PubMed

    Angeles-Han, Sheila T; Rabinovich, Consuelo Egla

    2016-09-01

    The review provides updates on novel risk markers for the development of pediatric inflammatory uveitis and a severe disease course, on treatment of refractory disease, and on the measurement of visual outcomes. There are several new genetic markers, biomarkers, and clinical factors that may influence a child's uveitis disease course. It is important to identify children at risk for poor visual outcomes and who are refractory to traditional therapy. Racial disparities have recently been reported. We describe agents of potential benefit. In addition, we discuss the importance of patient reported outcomes in this population. Uveitis can lead to vision-threatening complications. Timely and aggressive treatment of children identified to be at risk for a severe uveitis course may lead to improved outcomes.

  19. Transplantation of autoimmune regulator-encoding bone marrow cells delays the onset of experimental autoimmune encephalomyelitis.

    PubMed

    Ko, Hyun-Ja; Kinkel, Sarah A; Hubert, François-Xavier; Nasa, Zeyad; Chan, James; Siatskas, Christopher; Hirubalan, Premila; Toh, Ban-Hock; Scott, Hamish S; Alderuccio, Frank

    2010-12-01

    The autoimmune regulator (AIRE) promotes "promiscuous" expression of tissue-restricted antigens (TRA) in thymic medullary epithelial cells to facilitate thymic deletion of autoreactive T-cells. Here, we show that AIRE-deficient mice showed an earlier development of myelin oligonucleotide glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). To determine the outcome of ectopic Aire expression, we used a retroviral transduction system to over-express Aire in vitro, in cell lines and in bone marrow (BM). In the cell lines that included those of thymic medullary and dendritic cell origin, ectopically expressed Aire variably promoted expression of TRA including Mog and Ins2 (proII) autoantigens associated, respectively, with the autoimmune diseases multiple sclerosis and type 1 diabetes. BM chimeras generated from BM transduced with a retrovirus encoding Aire displayed elevated levels of Mog and Ins2 expression in thymus and spleen. Following induction of EAE with MOG(35-55), transplanted mice displayed significant delay in the onset of EAE compared with control mice. To our knowledge, this is the first example showing that in vivo ectopic expression of AIRE can modulate TRA expression and alter autoimmune disease development. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Major retinal autoantigens remain stably expressed during all stages of spontaneous uveitis.

    PubMed

    Deeg, Cornelia A; Hauck, Stefanie M; Amann, Barbara; Kremmer, Elisabeth; Stangassinger, Manfred; Ueffing, Marius

    2007-07-01

    Equine recurrent uveitis (ERU) is a valuable model for autoimmune diseases, since it develops frequently and occurs spontaneously. We investigated the overall expression level of three major retinal autoantigens in normal retinas and various ERU stages. Analysis of retinal proteomes of both, healthy and diseased retinas revealed an almost unaffected expression of IRBP, S-antigen and cRALBP in ERU cases. Validation of these findings with western blots and immunohistochemistry confirmed constant to increased expression of these autoantigens, although loss of their physiological expression sites within retina is evident. In contrast to stable expression of autoantigens, rhodopsin, the major component of phototransduction in photoreceptors, disappeared from destructed retinas. These results explain persistent uveitic attacks even in severely damaged eyes and draw the attention to further investigations of biological pathways and regulations in autoimmune target tissues.

  1. Uveitis in Children

    PubMed Central

    Angeles-Han, Sheila T.; Rabinovich, C. Egla

    2016-01-01

    Purpose of review This review provides updates on novel risk markers for the development of pediatric inflammatory uveitis and a severe disease course, on treatment of refractory disease, and on the measurement of visual outcomes. Recent findings There are several new genetic markers, biomarkers and clinical factors that may influence a child’s uveitis disease course. It is important to identify children at risk for poor visual outcomes and who are refractory to traditional therapy. Racial disparities have recently been reported. We describe agents of potential benefit. In addition, we discuss the importance of patient reported outcomes in this population. Summary Uveitis can lead to vision threatening complications. Timely and aggressive treatment of children identified to be at risk for a severe uveitis course may lead to improved outcomes. PMID:27328333

  2. Immunological Characterization of Intraocular Lymphoid Follicles in a Spontaneous Recurrent Uveitis Model.

    PubMed

    Kleinwort, Kristina J H; Amann, Barbara; Hauck, Stefanie M; Feederle, Regina; Sekundo, Walter; Deeg, Cornelia A

    2016-08-01

    Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and signaling of immune cells in intraocular tertiary lymphoid tissues. Ectopic lymphoid tissues were located preferentially in the iris, ciliary body, and retina at the ora serrata of horses with naturally-occurring ERU. The majority of cells in the tertiary lymphoid follicles were T cells with a scattered distribution of B cells and PNA+ cells interspersed. A fraction of T cells was additionally positive for memory cell marker CD45RO. Almost all cells coexpressed CD166, a molecule associated with activation and transmigration of T cells into inflamed tissues. Several transcription factors that govern immune cell responses were detectable in the tertiary lymphoid follicles, among them Zap70, TFIIB, GATA3, and IRF4. A high expression of the phosphorylated signal transducers and activators of transcription (STAT) proteins 1 and 5 were found at the margin of the structures. Cellular composition and structural organization of these inflammation-associated tertiary lymphoid tissue structures and the expression of markers of matured T and B cells point to highly organized adaptive immune responses in these follicles in spontaneous recurrent uveitis.

  3. [Uveitis in spondyloarthritis patients and its association with HLA-B27 histocompatibility antigen: prospective study].

    PubMed

    Razumova, I Yu; Godzenko, A A; Vorob'eva, O K; Guseva, I A

    2016-01-01

    to perform a prospective study of clinical presentation and course of uveitis in spondyloarthritis (SpA) patients as well as its association with the HLA-B27 histocompatibility antigen. The study included 219 patients with uveitis, all tested for HLA-B27 antigen and various infections (viral, bacterial, and parasitic) as well as examined for locomotive system involvement. The presence of the HLA-B27 antigen was determined in 142 (64.8%) out of 219 patients, of them 87 were diagnosed with an entity of the SpA group. The remaining 77 (35.2%) patients appeared to be HLA-B27-negative, but 13 were still diagnosed with an entity of the SpA group. There were 10 (4.6%) patients with 2 or more diseases from the SpA group («clinical decussation»). When comparing the two groups of HLA-B27-positive and negative patients having both SpA and uveitis, no statistically significant difference was found as to the age of onset, site, frequency of attacks, and uni- or bilateral involvement (p>0.05). We also performed a comparison of HLA-B27-positive and negative patients with no account to their SpA status and revealed a higher complication rate in those that were «negative» (p<0.0001), which can be explained by the fact that HLA-B27-negative patients often have autoimmune or infectious uveitis of different origin notable for long attacks and short remissions. Assessing the site and course of uveitis as well as HLA-B27 testing of uveitis patients has proved important for etiological diagnosis. Diseases of the SpA group have been shown to be 6.7 times more common in HLA-B27-positive patients as compared to HLA-B27-negative ones. Clinical presentation of uveitis in the presence of SpA in both HLA-B27-positive and negative patients resembles that of idiopathic uveitis - an independent HLA-B27-associated syndrome (р>0.05). Cases of «decussation» between entities of the SpA group are usually more severe in terms of clinical presentation and course of uveitis and are associated with

  4. Unraveling the equine lymphocyte proteome: differential septin 7 expression associates with immune cells in equine recurrent uveitis.

    PubMed

    Degroote, Roxane L; Hauck, Stefanie M; Amann, Barbara; Hirmer, Sieglinde; Ueffing, Marius; Deeg, Cornelia A

    2014-01-01

    Equine recurrent uveitis is a spontaneous, lymphocyte-driven autoimmune disease. It affects horses worldwide and presents with painful remitting-relapsing inflammatory attacks of inner eye structures eventually leading to blindness. Since lymphocytes are the key players in equine recurrent uveitis, we were interested in potential changes of their protein repertoire which may be involved in disease pathogenesis. To create a reference for differential proteome analysis, we first unraveled the equine lymphocyte proteome by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequently identified 352 protein spots. Next, we compared lymphocytes from ERU cases and healthy horses with a two-dimensional fluorescence difference in gel electrophoresis approach. With this technique, we identified seven differentially expressed proteins between conditions. One of the significantly lower expressed candidates, septin 7, plays a role in regulation of cell shape, motility and migration. Further analyses revealed T cells as the main cell type with decreased septin 7 abundance in equine recurrent uveitis. These findings point to a possible pathogenetic role of septin 7 in this sight-threatening disease.

  5. Equine recurrent uveitis: the European viewpoint.

    PubMed

    Spiess, B M

    2010-03-01

    Equine recurrent uveitis (ERU) has always been and still is an important disease with a significant impact on the horse industry in Europe, with a prevalence of 8-10%. The need to understand and manage the disease has spurred the development of veterinary ophthalmology in general, although the aetiology of the disease remains the subject of intense discussion. It is most probably an autoimmune disease triggered, at least in Europe, in the majority of cases by Leptospira spp. The therapy of ERU has evolved over the centuries from various methods of bloodletting to rational medical therapy using mydriatics and steroidal and nonsteroidal anti-inflammatory drugs, to surgical therapies, such as vitrectomy or implantation of cyclosporin-releasing devices. In Europe, pars plana vitrectomy in horses testing positive for Leptospira spp. appears to be the most successful form of therapy at the present time.

  6. [Therapy for childhood uveitis: biologics: too often--too late?].

    PubMed

    Mackensen, F; Lutz, T

    2011-03-01

    Pediatric uveitis differs from uveitis seen in adulthood not only because of the uveitis presentation and severity of disease but also by a worse prognosis and age-specific problems that may occur under therapy. Biologics are selective acting proteins that are manufactured by biotechnology. The greatest amount of knowledge to date exists for the TNF alpha blocking agents. Experimental and clinical studies showed that TNF alpha plays a significant role in the process of intraocular inflammation, so it was a logical step to use TNF blocking agents in uveitis therapy. Randomized controlled studies are rare, but pooled data (as presented here) of case series published show good evidence for the efficacy especially of infliximab and adalimumab. It is to be hoped that blindness and severe sight disabilities can be further reduced by this treatment in the future. From pediatric rheumatology we have learned about even newer biologics. With this review we want to show the weaknesses and strengths of therapy with biologics and want to help in choosing this treatment at the indicated time point in the disease.

  7. Emerging Role of Antioxidants in the Protection of Uveitis Complications

    PubMed Central

    Yadav, Umesh C S; Kalariya, Nilesh M; Ramana, Kota V

    2011-01-01

    Current understanding of the role of oxidative stress in ocular inflammatory diseases indicates that antioxidant therapy may be important to optimize the treatment. Recently investigated antioxidant therapies for ocular inflammatory diseases include various vitamins, plant products and reactive oxygen species scavengers. Oxidative stress plays a causative role in both non-infectious and infectious uveitis complications, and novel strategies to diminish tissue damage and dysfunction with antioxidant therapy may ameliorate visual complications. Preclinical studies with experimental animals and cell culture demonstrate significance of anti-inflammatory effects of a number of promising antioxidant agents. Many of these antioxidants are under clinical trial for various inflammatory diseases other than uveitis such as cardiovascular, rheumatoid arthritis and cancer. Well planned interventional clinical studies of the ocular inflammation will be necessary to sufficiently investigate the potential medical benefits of antioxidant therapies for uveitis. This review summarizes the recent investigation of novel antioxidant agents for ocular inflammation, with selected studies focused on uveitis. PMID:21182473

  8. Rabbit hunter uveitis: case report of tularemia uveitis.

    PubMed

    Terrada, Céline; Azza, Said; Bodaghi, Bahram; Le Hoang, Phuc; Drancourt, Michel

    2016-09-01

    Literature reports on ophthalmological manifestations related to tularemia, a zoonose caused by the bacterium Francisella tularensis, largely refer to Parinaud's oculoglandular syndrome, which consists of the association of conjunctivitis with preauricular lymphadenitis. In this paper, we report a case of intraocular inflammation during tularemia infection. A 52-year-old Caucasian man was diagnosed with unilateral uveitis. The uveitis was posterior, with a 2+ vitritis and a large yellowish lesion involving the macula with an overlying sub-retinal detachment, extending inferiorly, and subretinal hemorrhages. Fluorescein angiography showed a late hyperfluorescence with focal vascular leakage. Ultrasound biomicroscopy confirmed the presence of a 3.8 mm parietal granuloma with a few calcifications in the left eye. While extensive work-up eliminated any other infectious and non-infectious etiology, tularemia was diagnosed by advanced serology consisting of two-dimensional Western-immunoblotting. The patient, a hunter, recalled having killed rabbits in the days before the symptoms appeared. Uveitis was rapidly controlled following treatment with doxycycline, yet three years after initiation of the treatment, the patient still complained of loss of vision in the left eye with a central scotoma. Posterior uveitis may be an infrequent manifestation of tularemia infection, and therefore this infection should be considered in the differential diagnosis of intraocular inflammation in areas where F. tularensis is endemic.

  9. Drug-induced uveitis

    PubMed Central

    2013-01-01

    A number of medications have been associated with uveitis. This review highlights both well-established and recently reported systemic, topical, intraocular, and vaccine-associated causes of drug-induced uveitis, and assigns a quantitative score to each medication based upon criteria originally described by Naranjo and associates. PMID:23522744

  10. Small molecules as therapy for uveitis: a selected perspective of new and developing agents.

    PubMed

    Pleyer, Uwe; Algharably, Engi Abdel-Hady; Feist, Eugen; Kreutz, Reinhold

    2017-09-01

    Intraocular inflammation (uveitis) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs and more recently biologics as immune modulatory agents. The purpose of this article is to identify the role of new treatment approaches focusing on small molecules as therapeutic option in uveitis. Areas covered: A MEDLINE database search was conducted through February 2017 using the terms 'uveitis' and 'small molecule'. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included. Both, results from experimental as well as clinical research in this field were included. Since this field is rapidly evolving, a selection of promising agents had to be made. Expert opinion: Small molecules may interfere at different steps of the inflammatory cascade and appear as an interesting option in the treatment algorithm of uveitis. Because of their highly targeted molecular effects and their favorable bioavailability with the potential of topical application small molecules hold great promise. Nevertheless, a careful evaluation of these agents has to be made, since current experience is almost exclusively based on experimental uveitis models and few registered trials.

  11. Management of pediatric uveitis

    PubMed Central

    Wentworth, Bailey A.; Freitas-Neto, Clovis A.

    2014-01-01

    Pediatric uveitis is a topic of special interest not only because of the unique diagnostic and therapeutic challenges but also because of the lifetime burden of vision loss if the problem is not adequately treated, as well as the economic and psychological toll on the family. Often, uveitis in children is discovered as part of a routine eye exam; this silent, insidious inflammation can be difficult to treat and can lead to further complications if not handled skillfully. Corticosteroids have long been the mainstay of therapy; however, the significant associated side effects mandate a corticosteroid-sparing therapeutic regimen in pursuit of remission. In this review, we cover the therapeutic options for pediatric uveitis, specifically focusing on the most common non-infectious varieties, juvenile idiopathic arthritis-associated uveitis and pars planitis. PMID:24991418

  12. Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

    PubMed

    Dick, Andrew D; Rosenbaum, James T; Al-Dhibi, Hassan A; Belfort, Rubens; Brézin, Antoine P; Chee, Soon Phaik; Davis, Janet L; Ramanan, Athimalaipet V; Sonoda, Koh-Hei; Carreño, Ester; Nascimento, Heloisa; Salah, Sawsen; Salek, Sherveen; Siak, Jay; Steeples, Laura

    2018-05-01

    An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations

  13. Human papilloma virus vaccine associated uveitis.

    PubMed

    Holt, Henry D; Hinkle, David M; Falk, Naomi S; Fraunfelder, Frederick T; Fraunfelder, Frederick W

    2014-03-01

    To report a possible association between human papilloma virus (HPV) vaccination and uveitis. Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

  14. [Effect of melatonin instillations on the clinical course of experimental uveitis and biochemical processes in tears and aqueous humor].

    PubMed

    Chesnokova, N B; Beznos, O V; Lozinskaya, N A; Beyshenova, G A; Nesterova, T V

    2016-01-01

    Acute immunogenic uveitis was modeled in rabbits via the subcutaneous and intravitreal injections of normal horse serum. We studied the effect of instillations of 0.1% melatonin solution on the clinical course of uveitis and biochemical parameters of tear fluid and aqueous humor: antioxi-dant activity, protein concentration and α(2)-macroglobulin level. Melatonin instillations decreased clinical manifestations of uveitis. We found that the antioxidant activity in tears of the rabbits treated with melatonin was substantially higher and the α(2)-macroglobulin level lower than in untreated animals. Antioxidant activity in aqueous humor taken on day 10 of uveitis was also twice higher while protein and α(2)-macroglobulin levels were 1.5-2 times lower than in untreated animals. These data indicate that instillations of melatonin increase the local antioxidant activity and decrease the acuity of inflammation and permeability of hematoophthalmic barrier in uveitis.

  15. Increased KPI containing amyloid precursor protein in experimental autoimmune encephalomyelitis brains.

    PubMed

    Beilin, Orit; Karussis, Dimitrios M; Korczyn, Amos D; Gurwitz, David; Aronovich, Ramona; Mizrachi-Kol, Rachel; Chapman, Joab

    2007-04-16

    Amyloid precursor protein can be translated from three alternatively spliced mRNAs. We measured levels of amyloid precursor protein isoforms containing the Kunitz protease inhibitor domain (KPIAPP), and amyloid precursor protein without the Kunitz protease inhibitor domain (KPIAPP) in brain homogenates of acute experimental autoimmune encephalomyelitis mice. At the preclinical phase of the disease, both KPIAPP and KPIAPP levels were significantly higher in homogenates from brains of autoimmune encephalomyelitis mice, whereas at the acute phase of the disease only KPIAPP remained significantly elevated compared with controls. At the recovery phase, no differences were observed between the groups. The early and isoform-specific elevation of KPIAPP in autoimmune encephalomyelitis mice suggests a possible role for amyloid precursor protein in the immune response mediating the disease.

  16. The Dexamethasone Intravitreal Implant for Noninfectious Uveitis: Practice Patterns Among Uveitis Specialists.

    PubMed

    Burkholder, Bryn M; Moradi, Ahmadreza; Thorne, Jennifer E; Dunn, James P

    2015-01-01

    To describe the practice patterns and perceptions of uveitis specialists regarding the use of the intravitreal dexamethasone (DEX) implant for the treatment of noninfectious uveitis. We invited uveitis specialists to participate in an anonymous online survey. Among the 45 respondents, 76.5% identified uveitic macular edema as the most common clinical finding for which they use the DEX implant. The most common contraindications to DEX implantation were aphakia and glaucoma requiring >2 medications. Nearly two-thirds (64.3%) felt that the advent of the DEX implant did not change the frequency with which they used the fluocinolone acetonide (FA) implant, and about one-third (32.3%) preferred to use at least one DEX implant, before committing a patient to an FA implant. Uveitis physicians use the DEX implant for a wide range of clinical findings and uveitic diagnoses. There was no clear consensus on preferences regarding the use of DEX versus FA implants.

  17. Pediatric uveitis: new and future treatments

    PubMed Central

    Mehta, Preema J.; Alexander, Janet L.; Sen, H. Nida

    2017-01-01

    Purpose of review Pediatric uveitis is relatively uncommon, accounting for only 5–10% of all patients with uveitis. However, owing to high prevalence of complications and devastating outcomes, its lifetime burden can be significant. Recent findings Immunomodulatory therapy has been associated with better outcomes in noninfectious pediatric uveitis. However, effective treatments are limited by medication-related complications, including multiorgan toxicities and systemic side effects. Summary We review the current therapies available to treat pediatric uveitis, discuss novel and future therapies, and provide clinical recommendations utilizing these new agents. The consideration for treatment regimens in noninfectious pediatric uveitis is multifactorial. Understanding past, present, and future technology will aid in treatment of a complex and refractory disease. PMID:23872814

  18. Association of systemic lupus erythematosus with uveitis.

    PubMed

    Gallagher, Kevin; Viswanathan, Ananth; Okhravi, Narciss

    2015-10-01

    Systemic lupus erythematosus (SLE) can be associated with uveitis. The reported prevalence of SLE in patients with uveitis varies from 0.1% to 4.8%. Accordingly, the positive predictive value of antinuclear antibody testing in diagnosing SLE in a patient with uveitis varies enormously. An accurate estimate of SLE prevalence in uveitis is needed to establish the value of routine antinuclear antibody testing in patients with uveitis. A literature review using the Medline database was performed to find studies reporting data on uveitis etiology from January 1, 1984, to March 20, 2015. Studies were included where there were sufficient data to draw conclusions on the prevalence of SLE as an etiological factor in uveitis. Data for 53 315 patients were reviewed and 63 studies from 30 countries were included. The prevalence of SLE as a cause of uveitis was estimated to be 0.47% (95% CI, 0.41%-0.53%). The positive predictive value of routine antinuclear antibody testing was 2.9% (95% CI, 2.65%-3.19%). Systemic lupus erythematosus is a rare cause of uveitis. Routine antinuclear antibody testing has a low positive predictive value for SLE. These data suggest such testing should be reserved for patients where there is a higher pretest probability of SLE.

  19. Anti-interferon-gamma antibodies in the treatment of autoimmune diseases.

    PubMed

    Skurkovich, Boris; Skurkovich, Simon

    2003-02-01

    Interferon (IFN)-gamma is an important immune regulator in normal immunity. When IFN gamma production is disturbed, various autoimmune diseases (ADs) can develop, in which we suggest that anti-IFN gamma could have a beneficial effect. Depending on the cell type in which IFN gamma synthesis is disturbed, different clinical manifestations may result. We have also proposed to remove tumor necrosis factor (TNF)-alpha, together with certain types of IFNs, to treat various ADs and AIDS, also an autoimmune condition. Anti-IFN gamma has been tested in several T-helper cell (Th1) ADs, including rheumatoid arthritis (RA), multiple sclerosis (MS), corneal transplant rejection, uveitis, Type I diabetes, schizophrenia (anti-IFN gamma and anti-TNF alpha), and various autoimmune skin diseases (alopecia areata, psoriasis vulgaris, vitiligo, pemphigus vulgaris and epidermolysis bullosa). A strong, sometimes striking, therapeutic response followed administration of anti-IFN gamma, indicating that it may be a promising therapy for Th1 ADs.

  20. Sarcoidosis and uveitis.

    PubMed

    Jamilloux, Yvan; Kodjikian, Laurent; Broussolle, Christiane; Sève, Pascal

    2014-08-01

    Uveitis is a frequent (20-50%) and early feature of sarcoidosis. Typical sarcoid uveitis presents with mutton-fat keratic precipitates, iris nodules, and anterior and posterior synechiae. Posterior involvement includes vitreitis, vasculitis, and choroidal lesions. Cystoid macular edema is the most important and sight-threatening consequence. Histologic proof from a biopsy is the gold standard for the diagnosis of ocular sarcoidosis. An international workshop has recently established diagnostic criteria for sarcoidosis uveitis when biopsy is unavailable or negative: these are based on a combination of ophthalmological findings and laboratory tests. The value of recent techniques, such as PET-scan and endoscopic ultrasound-guided, fine-needle aspiration of intrathoracic nodes needs to be assessed in future studies. Corticosteroids are the mainstay treatment for sarcoidosis. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema and occlusive vasculitis. In up to 15% of cases, additional immunosuppression is used, including methotrexate, azathioprine, and mycophenolate mofetil. Infliximab and adalimumab have been recently proposed for the treatment of refractory or sight-threatening systemic sarcoidosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Use of Immunomodulatory Drugs at a Uveitis Clinic.

    PubMed

    Millán-Longo, Claudia; Peiteado, Diana; Schlincker, Armelle; Hidalgo, Ventura; Pieren, Amara; Balsa, Alejandro; de Miguel, Eugenio

    2017-11-10

    The treatment of noninfectious uveitis includes steroids and immunomodulatory drugs, the use of which has increased in the last few years, and the options have been enriched with the development of new treatments. However, clear therapeutic guidelines and protocols have not been developed. The purpose is to analyze the response to the drugs used and the characteristics of the patients treated at a multidisciplinary uveitis clinic. Observational and retrospective study of the patients attended to from January 2012 to December 2015. Infectious, posttraumatic and postoperative uveitis, as well as masquerade syndrome, were excluded. Two hundred six patients were included. Overall, 58.80% had uveitis without association of systemic disease, mostly idiopathic uveitis, and 35.65% had uveitis with systemic involvement, mainly related to spondyloarthritis. Uveitis without systemic association and anterior uveitis achieved disease control with local treatment more frequently than others (p=.002 and p <.001, respectively). In all, 49.76% of the patients required systemic treatment. Among those treated with immunomodulators, 53.26% needed a second drug and 31.52% needed a third drug. Women required immunomodulators more often than men (P=.042). Methotrexate was the most widely used immunomodulator. Posterior uveitis responded less favorably to the second immunomodulator than anterior uveitis (p=.006). Almost half of the patients needed an immunomodulatory drug and some of them required successive drug changes. Intermediate uveitis was the most treatment-refractory uveitis. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  2. Suppressor of cytokine signaling 1 (SOCS1) mitigates anterior uveitis and confers protection against ocular HSV-1 infection.

    PubMed

    Yu, Cheng-Rong; Hayashi, Kozaburo; Lee, Yun Sang; Mahdi, Rashid M; Shen, De Fen; Chan, Chi-Chao; Egwuagu, Charles E

    2015-04-01

    Immunological responses to pathogens are stringently regulated in the eye to prevent excessive inflammation that damage ocular tissues and compromise vision. Suppressors of cytokine signaling (SOCS) regulate intensity/duration of inflammatory responses. We have used SOCS1-deficient mice and retina-specific SOCS1 transgenic rats to investigate roles of SOCS1 in ocular herpes simplex virus (HSV-1) infection and non-infectious uveitis. We also genetically engineered cell-penetrating SOCS proteins (membrane-translocating sequence (MTS)-SOCS1, MTS-SOCS3) and examined whether they can be used to inhibit inflammatory cytokines. Overexpression of SOCS1 in transgenic rat eyes attenuated ocular HSV-1 infection while SOCS1-deficient mice developed severe non-infectious anterior uveitis, suggesting that SOCS1 may contribute to mechanism of ocular immune privilege by regulating trafficking of inflammatory cells into ocular tissues. Furthermore, MTS-SOCS1 inhibited IFN-γ-induced signal transducers and activators of transcription 1 (STAT1) activation by macrophages while MTS-SOCS3 suppressed expansion of pathogenic Th17 cells that mediate uveitis, indicating that MTS-SOCS proteins maybe used to treat ocular inflammatory diseases of infectious or autoimmune etiology.

  3. A comprehensive review and update on the non-biologic treatment of adult noninfectious uveitis: part I.

    PubMed

    Lee, Kyungmin; Bajwa, Asima; Freitas-Neto, Clovis A; Metzinger, Jamie Lynne; Wentworth, Bailey A; Foster, C Stephen

    2014-10-01

    Treatment of adult, noninfectious uveitis remains a challenge for ophthalmologists around the world. The disease accounts for almost 10% of preventable blindness in the US and can be idiopathic or associated with infectious and systemic disorders. Strong evidence is still emerging to indicate that pharmacologic strategies presently used in rheumatologic or autoimmune disease may be translated to the treatment of intraocular inflammation. Corticosteroid monotherapy is widely regarded as wholly inappropriate, due to the unfavorable risk/benefit profile and poor long-term outcomes. Treatment plans have shifted away from low-dose, chronic corticosteroid therapy for maintenance, towards medium- to high-dose therapy for acute inflammation, followed immediately by initiation of immunomodulatory therapy. These therapies follow the 'stepladder approach', whereby least to more aggressive therapies are trialed to induce remission of inflammation, eventually without corticosteroids of any form (topical, local and systemic). This two-part review gives a comprehensive overview of the existing medical treatment options for patients with adult, noninfectious uveitis, as well as important advances for the treatment of ocular inflammation. Part I covers classic immunomodulation and latest information on corticosteroid therapy. The hazard of chronic corticosteroid use for the treatment of adult, noninfectious uveitis is well-documented. Corticosteroid-sparing therapies, which offer a very favorable risk-benefit profile when administered properly, should be substituted.

  4. Tuberculous Posterior Sclero-Uveitis with Features of Vogt-Koyanagi-Harada Uveitis: An Unusual Case.

    PubMed

    Kalogeropoulos, Dimitrios; Kitsos, George; Konstantinidis, Athanasios; Gartzonika, Constantina; Svarna, Evgenia; Malamos, Konstantinos; Katsanevakis, Emmanouil; Kalogeropoulos, Chris

    2017-04-08

    BACKGROUND Ocular tuberculosis (TB) is a clinical entity that presents with a wide range of clinical manifestations. It is regarded as an extremely challenging condition from the point of view of diagnostic approach and calls for early diagnosis and prompt treatment, as it can potentially lead to blindness. CASE REPORT This is a case report of a 32-year-old male from southern India who has been living and working in Greece over the last 10 years and presented with 2-week history of pain and progressive visual impairment of his left eye. He underwent a thorough clinical ophthalmological examination and imaging of the fundus, and the findings were consistent with uveitis. However, the manifestations of the inflammation were complicated as they included features that could be attributed mainly to Vogt-Koyanagi-Harada (VKH) disease and tuberculous serpiginous-like uveitis. Therefore, a systemic evaluation, together with specific laboratory and paraclinical investigations, were carried out to define the etiology of the inflammation and develop an optimal therapeutic plan. Taking into account specific findings from the chest imaging, a positive purified protein derivative (PPD) skin test, and sputum cultures positive for Mycobacterium tuberculosis (MTB), we set a diagnosis of posterior sclero-uveitis and started our patient on anti-tuberculous treatment. CONCLUSIONS This case reveals an atypical manifestation of tuberculous sclero-uveitis imitating Vogt-Koyanagi-Harada disease together with a few characteristics of serpiginous-like tuberculous uveitis, emphasizing the fact that tuberculosis should always be included in the differential diagnosis of uveitis when there is no obvious underlying disease.

  5. Uveitis

    MedlinePlus

    ... the uveitis is caused by a body-wide (systemic) infection, you may be given antibiotics. You may ... vision Prevention If you have a body-wide (systemic) infection or disease, treating the condition will prevent ...

  6. Uveitis in horses induced by interphotoreceptor retinoid-binding protein is similar to the spontaneous disease.

    PubMed

    Deeg, Cornelia A; Thurau, Stephan R; Gerhards, Hartmut; Ehrenhofer, Marion; Wildner, Gerhild; Kaspers, Bernd

    2002-09-01

    Equine recurrent uveitis (ERU) is an inflammatory eye disease with high similarity to uveitis in man. It is the only spontaneous animal model for uveitis and the most frequent eye disease in horses affecting up to 10% of the population. To further investigate the pathophysiology of ERU we now report the establishment of an inducible uveitis model in horses. An ERU-like disease was elicited in seven out of seven horses by injection of interphotoreceptor retinoid-binding protein (IRBP) in complete Freund's adjuvant. Control horses did not develop uveitis. The disease model is characterized by a highly reproducible disease course and recurrent episodes with an identical time course elicited in all horses by repeated IRBP injections. The histology revealed the formation of lymphoid follicle-like structures in the eyes and an intraocular infiltration dominated by CD3(+) lymphocytes, morphological patterns typical for the spontaneous disease. Antigen-specific T cell proliferation of PBL was monitored prior to clinical uveitis and during disease episodes. An initial T cell response to IRBP-derived peptides was followed by epitope spreading to S-antigen-derived peptides in response to subsequent immunizations. Thus, horse experimental uveitis represents a valuable disease model for comparative studies with the spontaneous disease and the investigation of immunomodulatory therapeutic approaches after onset of the disease.

  7. Equine recurrent uveitis: treatment.

    PubMed

    Curling, Amanda

    2011-06-01

    Equine recurrent uveitis has traditionally been treated with medical management to reduce ocular inflammation and control pain during a single episode. Newer management methods include surgical options such as cyclosporine implantation and vitrectomy. These methods were developed not only to control inflammation but also to eliminate the underlying cause of uveitis in order to prevent recurrence.

  8. Lymphocyte-dependent antibodies in uveitis.

    PubMed

    Pápai, I; Lehrner, J

    1976-01-01

    Lymphocyte-dependent antibodies were revealed in the serum of patients suffering from uveitis of various aetiologies. The serum was incubated with normal uveal tissue and the binding of non-immune human lymphocytes was investigated. In three cases of sympathetic ophthalmitis the lymphocytes accumulated around the melanine granules, while in another 17 patients with uveitis cases the lymphocytes accumulated around the capillaries. Uveal tissue incubated with control sera failed to bound lymphocytes. The lymphocytic infiltration in certain cases of chronic uveitis suggested the role of lymphocyte-mediating antibodies in the aetiology of these cases.

  9. Regulatory T cells control strain specific resistance to Experimental Autoimmune Prostatitis

    PubMed Central

    Breser, Maria L.; Lino, Andreia C.; Motrich, Ruben D.; Godoy, Gloria J.; Demengeot, Jocelyne; Rivero, Virginia E.

    2016-01-01

    Susceptibility to autoimmune diseases results from the encounter of a complex and long evolved genetic context with a no less complex and changing environment. Major actors in maintaining health are regulatory T cells (Treg) that primarily dampen a large subset of autoreactive lymphocytes escaping thymic negative selection. Here, we directly asked whether Treg participate in defining susceptibility and resistance to Experimental Autoimmune Prostatitis (EAP). We analyzed three common laboratory strains of mice presenting with different susceptibility to autoimmune prostatitis upon immunization with prostate proteins. The NOD, the C57BL/6 and the BALB/c mice that can be classified along a disease score ranging from severe, mild and to undetectable, respectively. Upon mild and transient depletion of Treg at the induction phase of EAP, each model showed an increment along this score, most remarkably with the BALB/c mice switching from a resistant to a susceptible phenotype. We further show that disease associates with the upregulation of CXCR3 expression on effector T cells, a process requiring IFNγ. Together with recent advances on environmental factors affecting Treg, these findings provide a likely cellular and molecular explanation to the recent rise in autoimmune diseases incidence. PMID:27624792

  10. Autoreactive Memory CD4+ T Lymphocytes that mediate Chronic Uveitis Reside in the Bone Marrow through STAT3-dependent Mechanisms

    PubMed Central

    Oh, Hyun-Mee; Yu, Cheng-Rong; Lee, YongJun; Chan, Chi-Chao; Maminishkis, Arvydas; Egwuagu, Charles E.

    2011-01-01

    Organ-specific autoimmune diseases are usually characterized by repeated cycles of remission and recurrent inflammation. However, where the autoreactive memory T-cells reside in-between episodes of recurrent inflammation is largely unknown. In this study, we have established a mouse model of chronic uveitis characterized by progressive photoreceptor-cell loss, retinal-degeneration, focal retinitis, retinal vasculitis, multifocal-choroiditis and choroidal neovascularization, providing for the first time a useful model for studying long-term pathological consequences of chronic inflammation of the neuroretina. We show that several months after inception of acute uveitis that autoreactive memory T-cells specific to retinal autoantigen, IRBP, relocated to bone marrow (BM). The IRBP-specific memory T-cells (IL-7RαHiLy6CHiCD4+) resided in BM in resting state but upon re-stimulation converted to IL-17-/IFN-γ-expressing effectors (IL-7RαLowLy6CLowCD4+) that mediated uveitis. We further show that T-cells from STAT3-deficient (CD4-STAT3KO) mice are defective in α4β1 and osteopontin expression; defects that correlated with inability of IRBP-specific memory CD4-STAT3KO T-cells to traffic into BM. We adoptively transferred uveitis to naïve mice using BM cells from WT mice with chronic uveitis but not BM cells from CD4-STAT3KO, providing direct evidence that memory T-cells that mediate uveitis reside in BM and that STAT3-dependent mechanism may be required for migration into and retention of memory T-cells in BM. Identifying BM as survival-niche for T-cells that cause uveitis, suggests that BM stromal cells that provide survival signals to autoreactive memory T-cells and STAT3-dependent mechanisms that mediate their relocation into BM, are attractive therapeutic targets that can be exploited to selectively deplete memory T-cells that drive chronic inflammation. PMID:21832158

  11. New developments in uveitis associated with HLA B27.

    PubMed

    Rosenbaum, James T

    2017-07-01

    Uveitis is the most common, clinically apparent, extra-articular manifestation of axial spondyloarthritis. This review summarizes recent publications related to this form of uveitis. Studies published since the start of 2015 address the worldwide prevalence of human leukocyte antigen (HLA) B27-associated uveitis, the prevalence of axial spondyloarthritis among patients with B27-associated acute anterior uveitis (AAU), the genetics of AAU and some of the clinical implications of AAU. Progress has been made in the treatment of uveitis in general and in the treatment of uveitis in association with spondyloarthropathy in particular. The pathogenesis of AAU might derive clues from the above as well as from an understanding of the microbiome and possibly from knowledge derived from uveitis in association with Ebola. Although HLA B27-associated uveitis has been recognized since 1973, a variety of recent observations shed new light on this common clinical association with spondyloarthritis.

  12. The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Birkner, Katharina; Wasser, Beatrice; Loos, Julia; Plotnikov, Alexander; Seger, Rony; Zipp, Frauke; Witsch, Esther; Bittner, Stefan

    2017-01-01

    Extracellular signal-regulated kinase (ERK) signaling plays a crucial role in regulating immune cell function and has been implicated in autoimmune disorders. To date, all commercially available inhibitors of ERK target upstream components, such as mitogen-activated protein (MAP) kinase/ERK kinase (MEKs), but not ERK itself. Here, we directly inhibit nuclear ERK translocation by a novel pharmacological approach (Glu-Pro-Glu (EPE) peptide), leading to an increase in cytosolic ERK phosphorylation during T helper (Th)17 cell differentiation. This was accompanied by diminished secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine influencing the encephalitogenicity of Th17 cells. Neither the production of the cytokine interleukin (IL)-17 nor the proliferation rate of T cells was affected by the EPE peptide. The in vivo effects of ERK inhibition were challenged in two independent variants of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Overall, ERK inhibition had only a very minor impact on the clinical disease course of EAE. This indicates that while ERK translocation might promote encephalitogenicity in T cells in vitro by facilitating GM-CSF production, this effect is overcome in more complex in vivo animal models of central nervous system (CNS) autoimmunity. PMID:28914804

  13. Ocular immunology in equine recurrent uveitis.

    PubMed

    Deeg, Cornelia A

    2008-09-01

    Equine recurrent uveitis (ERU) is a disease with high prevalence and relevance for the equine population, since it results in blindness. Over the last decade, important advancements have been made in our understanding of the underlying immune responses in this disease. ERU is mediated by an autoaggressive Th1 response directed against several retinal proteins. Interphotoreceptor-retinoid binding protein (IRBP) and cellular retinaldehyde-binding protein (CRALBP) are capable to induce ERU-like disease in experimental horses, with the unique possibility to activate relapses in a well-defined manner. Further, proteomic evidence now suggests that retinal Mueller glial cells (RMG) may play a fatal role in uveitic disease progression by directly triggering inflammation processes through the expression and secretion of interferon-gamma. Ongoing relapses in blind eyes can be associated with stable expression of the major autoantigens in ERU retinas. This review briefly summarizes the most significant developments in uveitis immune response research.

  14. The prevalence of autoimmune disease in patients with esophageal achalasia.

    PubMed

    Booy, J D; Takata, J; Tomlinson, G; Urbach, D R

    2012-04-01

    Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  15. The Association of Race with Childhood Uveitis

    PubMed Central

    Angeles-Han, Sheila T; McCracken, Courtney; Yeh, Steven; Jenkins, Kirsten; Stryker, Daneka; Travers, Curtis; Rouster-Stevens, Kelly; Vogler, Larry B.; Lambert, Scott R.; Drews-Botsch, Carolyn; Prahalad, Sampath

    2015-01-01

    Purpose To identify risk factors for a severe uveitis course among children with non-infectious uveitis. Design Retrospective cohort study Method This was a retrospective analysis of a prospectively collected database. Records of 94 children with uveitis were reviewed at enrollment and every 3-6 months (2011-2015). Severe uveitis was defined as a history of ocular complications or a visual acuity (VA) of ≤20/200. Children were compared by disease, VA, complications and race. Regression models were used to model risk factors for severe disease. When examining race, we focused on non-Hispanic African American and non-Hispanic White children only. Results Of 85 children with uveitis and complete ocular examinations, 27 (32%) had a history of a VA of ≤20/200. A subanalysis of non-Hispanic African American and White children showed an increased prevalence of VA ≤20/200 in non-Hispanic African Americans (18/25 (72%) vs. 4/43 (9%)). Non-Hispanic African Americans were more likely to be diagnosed at an older age (p=0.030), have intermediate uveitis (p=0.026), bilateral disease (p=0.032), a history of VA ≤20/50 (p=0.002), VA ≤20/200 (p<0.001), and a higher rate of complications (p<0.001). On multivariable analysis, non-Hispanic African American race was a significant predictor of blindness (OR=31.6, 95% CI (5.9– 168.5), p<0.001), after controlling for uveitis duration. Non-Hispanic African Americans also developed 2.2 times more unique complications per year of disease than non-Hispanic Whites when controlling for uveitis type and duration. Conclusions There appear to be racial differences in the outcomes of children with uveitis. Non-Hispanic African American children with non-juvenile idiopathic arthritis associated uveitis may have worse visual outcomes with increased vision loss and ocular complications. These findings highlight the need for future studies in minority populations. PMID:26255577

  16. Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis.

    PubMed

    Kaplan, Barbara L F

    2018-02-21

    Cannabinoid compounds refer to a group of more than 60 plant-derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one's ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

  17. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis

    PubMed Central

    Yeste, Ada; Nadeau, Meghan; Burns, Evan J.; Weiner, Howard L.; Quintana, Francisco J.

    2012-01-01

    The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3+ Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55 to promote the generation of Tregs by DCs. NP-treated DCs displayed a tolerogenic phenotype and promoted the differentiation of Tregs in vitro. Moreover, NPs carrying ITE and MOG35–55 expanded the FoxP3+ Treg compartment and suppressed the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis. Thus, NPs are potential new tools to induce functional Tregs in autoimmune disorders. PMID:22745170

  18. Role of IL-22– and TNF-α–Producing Th22 Cells in Uveitis Patients with Behçet’s Disease

    PubMed Central

    Kawazoe, Yuko; Imai, Ayano; Kawaguchi, Tatsushi; Horie, Shintaro; Keino, Hiroshi; Takahashi, Masayo; Mochizuki, Manabu

    2013-01-01

    Behçet’s disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet’s disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4+ T cells from the peripheral blood of Behçet’s disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti–TNF-α– and anti–IL-6–blocking Abs, Behçet’s disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22–producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet’s disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet’s disease. PMID:23630362

  19. Immunoglobulin E-Mediated Autoimmunity

    PubMed Central

    Maurer, Marcus; Altrichter, Sabine; Schmetzer, Oliver; Scheffel, Jörg; Church, Martin K.; Metz, Martin

    2018-01-01

    The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them. PMID:29686678

  20. Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2.

    PubMed

    Hauck, Stefanie M; Hofmaier, Florian; Dietter, Johannes; Swadzba, Margarete E; Blindert, Marcel; Amann, Barbara; Behler, Jennifer; Kremmer, Elisabeth; Ueffing, Marius; Deeg, Cornelia A

    2012-07-19

    Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative mass spectrometry based on label-free quantification of peak intensities across samples. We found a significant upregulation of complement and coagulation cascades and downregulation of negative paracrine regulators of canonical Wnt signalling including the Wnt signalling inhibitors DKK3 and SFRP2. Based on immunohistochemistry, both proteins are expressed in equine retina and suggest localisation to retinal Müller glial cells (RMG), which may be the source cells for these proteins. Furthermore, retinal expression levels and patterns of DKK3 change in response to ERU. Since many other regulated proteins identified here are associated with RMG cells, these cells qualify as the prime responders to autoimmune triggers. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Etanercept in methotrexate-resistant JIA-related uveitis.

    PubMed

    Saeed, Muhammad Usman; Raza, Syed Hamid; Goyal, Sudeshna; Cleary, Gavin; Newman, William David; Chandna, Arvind

    2014-01-01

    We report our results with systemic Etanercept in patients with juvenile idiopathic arthritis in a joint ophthalmology-rheumatology clinic at a tertiary hospital. Patients with JIA on Etanercept were identified from a dedicated uveitis database. A retrospective review of electronic and paper-based patient records was performed. Nine patients with JIA and current or previous treatment with Etanercept were identified, including six females and three males. Five patients with previous or current uveitis were noted. A further four were under observation for uveitis and required Etanercept for their joint disease. All nine patients had previously been taking Methotrexate, which had a suboptimal response in controlling arthritis or uveitis. Six out of nine patients did not show any uveitis activity at their last follow-up. Eyes of three patients still show signs of active inflammation in the anterior chamber (two on Etanercept and one off Etanercept). Severely impaired visual acuity (PL) was recorded in both eyes of one patient with long-standing persistent uveitis. Moderate visual loss in one eye of one patient was seen. The remaining seven patients did not show any significant loss of vision. Intraocular inflammation was not induced in any patient started on Etanercept. Etanercept may be useful in controlling JIA-related uveitis or arthritis in a pediatric patient when Methotrexate has had a suboptimal response in controlling the inflammatory activity.

  2. Anti-adalimumab antibodies in juvenile idiopathic arthritis-related uveitis.

    PubMed

    Leinonen, Sanna T; Aalto, Kristiina; Kotaniemi, Kaisu M; Kivelä, Tero T

    2017-01-01

    To evaluate the association of adalimumab trough levels and anti-adalimumab antibodies with activity of uveitis in juvenile idiopathic arthritis-related uveitis. This was a retrospective observational case series in a clinical setting at the Department of Ophthalmology, Helsinki University Hospital, Finland in 2014-2016. Thirty-one paediatric patients with chronic anterior juvenile idiopathic arthritis-related uveitis in 58 eyes and who had been on adalimumab ≥6 months were eligible for the study. Uveitis activity during adalimumab treatment, adalimumab trough levels and anti-adalimumab antibody levels were recorded. Anti-adalimumab antibody levels ≥12 AU /ml were detected in nine patients (29%). This level of anti-adalimumab antibodies was associated with a higher grade of uveitis (p<0.001), uveitis that was not in remission (p=0.001) and with lack of concomitant methotrexate therapy (p=0.043). In patients with anti-adalimumab antibody levels <12 AU/ml, higher serum trough levels did not associate with better control of uveitis (p=0.86). Adalimumab treatment might be better guided by monitoring anti-adalimumab antibody formation in treating JIA-related uveitis.

  3. SOCS3 deletion in T lymphocytes suppresses development of chronic ocular inflammation via upregulation of CTLA-4 and expansion of regulatory T cells.

    PubMed

    Yu, Cheng-Rong; Kim, Sung-Hye; Mahdi, Rashid M; Egwuagu, Charles E

    2013-11-15

    Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of the JAK/STAT pathway, and SOCS3 contributes to host immunity by regulating the intensity and duration of cytokine signals and inflammatory responses. Mice with Socs3 deletion in myeloid cells exhibit enhanced STAT3 signaling, expansion of Th1 and Th17 cells, and develop severe experimental autoimmune encephalomyelitis. Interestingly, development of the unique IL-17/IFN-γ double-producing (Th17/IFN-γ and Tc17/IFN-γ) subsets that exhibit strong cytotoxic activities and are associated with pathogenesis of several autoimmune diseases has recently been shown to depend on epigenetic suppression of SOCS3 expression, further suggesting involvement of SOCS3 in autoimmunity and tumor immunity. In this study, we generated mice with Socs3 deletion in the CD4 T cell compartment (CD4-SOCS3 knockout [KO]) to determine in vivo effects of the loss of Socs3 in the T cell-mediated autoimmune disease, experimental autoimmune uveitis (EAU). In contrast to the exacerbation of experimental autoimmune encephalomyelitis in myeloid-specific SOCS3-deleted mice, CD4-SOCS3KO mice were protected from acute and chronic uveitis. Protection from EAU correlated with enhanced expression of CTLA-4 and expansion of IL-10-producing regulatory T cells with augmented suppressive activities. We further show that SOCS3 interacts with CTLA-4 and negatively regulates CTLA-4 levels in T cells, providing a mechanistic explanation for the expansion of regulatory T cells in CD4-SOCS3 during EAU. Contrary to in vitro epigenetic studies, Th17/IFN-γ and Tc17/IFN-γ populations were markedly reduced in CD4-SOCS3KO, suggesting that SOCS3 promotes expansion of the Th17/IFN-γ subset associated with development of severe uveitis. Thus, SOCS3 is a potential therapeutic target in uveitis and other autoinflammatory diseases.

  4. The Brain Proteome of the Ubiquitin Ligase Peli1 Knock-Out Mouse during Experimental Autoimmune Encephalomyelitis.

    PubMed

    Lereim, Ragnhild Reehorst; Oveland, Eystein; Xiao, Yichuan; Torkildsen, Øivind; Wergeland, Stig; Myhr, Kjell-Morten; Sun, Shao-Cong; Berven, Frode S

    2016-09-01

    The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak. Brain samples from the frontal hemisphere, peripheral from the extensive inflammatory foci, were analyzed using TMT-labeling of sample pools, and the discovered proteins were verified in individual mice using label-free proteomics. The greatest proteomic differences between Peli1 knock-out and wild-type mice were observed at the disease peak. In Peli1 knock-out a higher degree of antigen presentation, increased activity of adaptive and innate immune cells and alterations to proteins involved in iron metabolism were observed during experimental autoimmune encephalomyelitis. These results unravel global effects to the brain proteome when abrogating Peli1 expression, underlining the importance of Peli1 as a regulator of the immune response also peripheral to inflammatory foci during experimental autoimmune encephalomyelitis. The proteomics data is available in PRIDE with accession PXD003710.

  5. Salate derivatives found in sunscreens block experimental autoimmune encephalomyelitis in mice

    PubMed Central

    Wang, Yanping; Marling, Steven J.; Plum, Lori A.; DeLuca, Hector F.

    2017-01-01

    UV light suppresses experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, in mice and may be responsible for the decreased incidence of MS in equatorial regions. To test this concept further, we applied commercially available sunblock preparations to mice before exposing them to UV radiation. Surprisingly, some of the sunblock preparations blocked EAE without UV radiation. Furthermore, various sunblock preparations had variable ability to suppress EAE. By examining the components of the most effective agents, we identified homosalate and octisalate as the components responsible for suppressing EAE. Thus, salates may be useful in stopping the progression of MS, and may provide new insight into mechanisms of controlling autoimmune disease. PMID:28739922

  6. Clinical characteristics, treatment and ocular complications of HLA-B27-related anterior uveitis and HLA-B27-non related anterior uveitis.

    PubMed

    Valls Pascual, Elia; Fontanilla Ortega, Pablo; Vicens Bernabeu, Elvira; Martínez-Costa, Lucía; Blanco Alonso, Ricardo

    2016-01-01

    Anterior uveitis is the most common type of intraocular inflammation. Those associated to HLA-B27 represent 18 to 32% of all anterior uveitis cases. To describe clinical characteristics, systemic treatment need, and frequency and type of ocular complications in a cohort of patients diagnosed with HLAB27-related anterior uveitis and in a cohort of patients diagnosed with HLA-B27 non-related anterior uveitis. To establish if statistically significant differences between both cohorts exist. We performed a retrospective cohort study including patients with non infectious anterior uveitis related and not related to the antigen HLA-B27. 162 patients were included, 58 diagnosed with HLA-B27-related anterior uveitis (cohort HLA-B27+1) and 104 diagnosed with HLA-B27- non related anterior uveitis (cohort HLA-B27-). No statistically significant differences were found regarding clinical characteristics between both cohorts with the exception of a higher frequency of recurrences in cohort HLA-B27+ and a higher frequency of chronic uveitis in cohort HLA-B27-. No differences were found regarding systemic treatment use nor development of ocular complications. In contrast to previous studies, we neither found higher male gender predominance in the cohort of patients with HLA-B27-related anterior uveitis, Nor did we find differences regarding average age, laterality, development of complications nor use of systemic corticosteroids. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. The Manchester Uveitis Clinic: the first 3000 patients--epidemiology and casemix.

    PubMed

    Jones, Nicholas P

    2015-04-01

    To demonstrate the demography, anatomical, and diagnostic classification of patients with uveitis attending the Manchester Uveitis Clinic (MUC), a specialist uveitis clinic in the northwest of England, UK. Retrospective retrieval of data on a computerized database incorporating all new referrals to MUC from 1991 to 2013. A total of 3000 new patients with uveitis were seen during a 22-year period. The anatomical types seen were anterior 46%; intermediate 11.1%; posterior 21.8%; and panuveitis 21.1%. The most common diagnoses were Fuchs heterochromic uveitis (11.5% of total), sarcoidosis-related uveitis (9.7%), idiopathic intermediate uveitis (7.9%), idiopathic acute anterior uveitis (7.0%), and toxoplasmosis (6.9%). Syphilis and tuberculosis-associated uveitis increased markedly in frequency during the study period. The uveitis casemix in this region reflects a predominantly white Caucasian population in a temperate country, but with changing characteristics owing to increasing immigration, enhanced diagnostic techniques, changes in referral pattern, and some real changes in disease incidence.

  8. Equine recurrent uveitis: classification, etiology, and pathogenesis.

    PubMed

    Curling, Amanda

    2011-06-01

    Equine recurrent uveitis is a cyclical disease that affects the eye and often leads to high management costs and unfavorable results, such as blindness. Research has improved understanding of the roles of various etiologies, especially leptospirosis, in initiating and perpetuating the pathogenesis of equine recurrent uveitis. Research has also led to the discovery that specific breeds and horses with specific coat color patterns may be predisposed to developing recurrent uveitis.

  9. Experimental Autoimmune Encephalomyelitis (EAE) as Animal Models of Multiple Sclerosis (MS).

    PubMed

    Glatigny, Simon; Bettelli, Estelle

    2018-01-08

    Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system (CNS) leading to the progressive destruction of the myelin sheath surrounding axons. It can present with variable clinical and pathological manifestations, which might reflect the involvement of distinct pathogenic processes. Although the mechanisms leading to the development of the disease are not fully understood, numerous evidences indicate that MS is an autoimmune disease, the initiation and progression of which are dependent on an autoimmune response against myelin antigens. In addition, genetic susceptibility and environmental triggers likely contribute to the initiation of the disease. At this time, there is no cure for MS, but several disease-modifying therapies (DMTs) are available to control and slow down disease progression. A good number of these DMTs were identified and tested using animal models of MS referred to as experimental autoimmune encephalomyelitis (EAE). In this review, we will recapitulate the characteristics of EAE models and discuss how they help shed light on MS pathogenesis and help test new treatments for MS patients. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  10. Autoimmune Retinopathy: Current Concepts and Practices (An American Ophthalmological Society Thesis).

    PubMed

    Sen, H Nida; Grange, Landon; Akanda, Marib; Fox, Austin

    2017-08-01

    To elicit and evaluate opinions in the diagnosis and management of nonparaneoplastic autoimmune retinopathy (npAIR) among members of the American Uveitis Society (AUS) and to further the development of consensus and criteria in the diagnosis and management of npAIR. We hypothesize that despite lack of any clear guidelines, a general consensus in the clinical diagnosis and treatment of npAIR exists among uveitis experts. A literature review was performed and a panel of uveitis experts was consulted to formulate a survey regarding the diagnosis and management of npAIR. An online survey of 10 questions was developed, and a link was distributed through the AUS membership discussion list. We defined "general consensus" as meaning that a majority (>50%) of the respondents provided the same answer to a question. Fifty-four members of the AUS responded to the survey. Thirty-eight members (70.4%) see one to three AIR patients per year. Greater than 50% consensus was reached on most items, particularly items relating to diagnostic features and tests (up to 96% consensus). The diagnosis and management of npAIR is challenging, as standardized clinical and laboratory diagnostic criteria have yet to be established. The results of this study support the presence of consensus regarding certain aspects of npAIR, but also indicate the need for developing clear clinical diagnostic criteria and treatment guidelines.

  11. Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients.

    PubMed

    Calvo-Río, Vanesa; Santos-Gómez, Montserrat; Calvo, Inmaculada; González-Fernández, M Isabel; López-Montesinos, Berta; Mesquida, Marina; Adán, Alfredo; Hernández, María Victoria; Maíz, Olga; Atanes, Antonio; Bravo, Beatriz; Modesto, Consuelo; Díaz-Cordovés, Gisela; Palmou-Fontana, Natalia; Loricera, Javier; González-Vela, M C; Demetrio-Pablo, Rosalía; Hernández, J L; González-Gay, Miguel A; Blanco, Ricardo

    2017-03-01

    To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral

  12. The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis.

    PubMed

    Sahin, Ozlem; Ziaei, Alireza

    2014-07-01

    This study was designed to investigate whether the antiinflammatory and antiproliferative activity of oral and intravitreal methotrexate (MTX) suppresses intraocular inflammation in patients with presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis. Interventional prospective study including three cases with presumed latent syphilitic uveitis treated with intravenous penicillin and oral MTX, and two cases with presumed tuberculosis-related uveitis treated with standard antituberculosis therapy and intravitreal MTX injections. Treatment efficacy of all cases was assessed by best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography. Four eyes of 3 patients with presumed latent syphilitic uveitis had improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema in 6 months with oral MTX therapy. No recurrence of intraocular inflammation was observed in 6 months to 18 months of follow-up period after cessation of MTX. Two eyes of two patients with presumed tuberculosis-related uveitis showed improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema after intravitreal injections of MTX. No recurrence of intraocular inflammation was observed in 6 months to 8 months of follow-up period after cessation of antituberculous therapy. For the first time in the treatment of presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis, we believe that MTX might have an adjunctive role to suppress intraocular inflammation, reduce uveitic macular edema, and prevent the recurrences of the diseases.

  13. Simvastatin as an Adjunct to Conventional Therapy of Non-infectious Uveitis: A Randomized, Open-Label Pilot Study.

    PubMed

    Shirinsky, Ivan V; Biryukova, Anastasia A; Shirinsky, Valery S

    2017-12-01

    Statins have been shown to reduce ocular inflammation in animal models of uveitis and to prevent development of uveitis in observational studies. There have been no experimental human studies evaluating statins' efficacy and safety in uveitis. In this study, we aimed to investigate efficacy and safety of simvastatin in patients with uveitis. For this single-center, open-label, randomized study, we enrolled patients with acute non-infectious uveitis. The patients were randomized to receive 40 mg simvastatin per day for 2 months in addition to conventional treatment or conventional treatment alone. The studied outcomes were the rate of steroid-sparing control of ocular inflammation, measures of ocular inflammation, intraocular pressure, and visual acuity. Fifty patients were enrolled in the study. Twenty-five patients were randomly assigned to receive simvastatin with conventional treatment and 25 to conventional treatment alone. Simvastatin was associated with significantly higher rates of steroid-sparing ocular inflammation control, decrease in anterior chamber inflammation, and improvement in visual acuity. The treatment was well tolerated, no serious adverse effects were observed. Our findings suggest that statins may have therapeutic potential in uveitis. These results need to be confirmed in double-blind, randomized, controlled studies.

  14. Remission of Intermediate Uveitis: Incidence and Predictive Factors.

    PubMed

    Kempen, John H; Gewaily, Dina Y; Newcomb, Craig W; Liesegang, Teresa L; Kaçmaz, R Oktay; Levy-Clarke, Grace A; Nussenblatt, Robert B; Rosenbaum, James T; Sen, H Nida; Suhler, Eric B; Thorne, Jennifer E; Foster, C Stephen; Jabs, Douglas A; Payal, Abhishek; Fitzgerald, Tonetta D

    2016-04-01

    To evaluate the incidence of remission among patients with intermediate uveitis; to identify factors potentially predictive of remission. Retrospective cohort study. Involved eyes of patients with primary noninfectious intermediate uveitis at 4 academic ocular inflammation subspecialty practices, followed sufficiently long to meet the remission outcome definition, were studied retrospectively by standardized chart review data. Remission of intermediate uveitis was defined as a lack of inflammatory activity at ≥2 visits spanning ≥90 days in the absence of any corticosteroid or immunosuppressant medications. Factors potentially predictive of intermediate uveitis remission were evaluated using survival analysis. Among 849 eyes (of 510 patients) with intermediate uveitis followed over 1934 eye-years, the incidence of intermediate uveitis remission was 8.6/100 eye-years (95% confidence interval [CI], 7.4-10.1). Factors predictive of disease remission included prior pars plana vitrectomy (PPV) (hazard ratio [HR] [vs no PPV] = 2.39; 95% CI, 1.42-4.00), diagnosis of intermediate uveitis within the last year (HR [vs diagnosis >5 years ago] =3.82; 95% CI, 1.91-7.63), age ≥45 years (HR [vs age <45 years] = 1.79; 95% CI, 1.03-3.11), female sex (HR = 1.61; 95% CI, 1.04-2.49), and Hispanic race/ethnicity (HR [vs white race] = 2.81; 95% CI, 1.23-6.41). Presence/absence of a systemic inflammatory disease, laterality of uveitis, and smoking status were not associated with differential incidence. Our results suggest that intermediate uveitis is a chronic disease with an overall low rate of remission. Recently diagnosed patients and older, female, and Hispanic patients were more likely to remit. With regard to management, pars plana vitrectomy was associated with increased probability of remission. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Remission of Intermediate Uveitis: Incidence and Predictive Factors

    PubMed Central

    Kempen, John H.; Gewaily, Dina Y.; Newcomb, Craig W.; Liesegang, Teresa L.; Kaçmaz, R. Oktay; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Sen, H. Nida; Suhler, Eric B.; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Payal, Abhishek; Fitzgerald, Tonetta D.

    2016-01-01

    Purpose To evaluate the incidence of remission among patients with intermediate uveitis; to identify factors potentially predictive of remission. Design Retrospective cohort study. Methods Involved eyes of patients with primary non-infectious intermediate uveitis at 4 academic ocular inflammation subspecialty practices, followed sufficiently long to meet the remission outcome definition, were studied retrospectively by standardized chart review data. Remission of intermediate uveitis was defined as a lack of inflammatory activity at ≥2 visits spanning ≥90 days in the absence of any corticosteroid or immunosuppressant medications. Factors potentially predictive of intermediate uveitis remission were evaluated using survival analysis. Results Among 849 eyes (of 510 patients) with intermediate uveitis followed over 1,934 eye-years, the incidence of intermediate uveitis remission was 8.6/100 eye-years (95% confidence interval (CI), 7.4–10.1). Factors predictive of disease remission included prior pars plana vitrectomy (PPV) (HR (vs. no PPV)=2.39; 95% CI, 1.42–4.00), diagnosis of intermediate uveitis within the last year (vs. diagnosis >5 years ago)=3.82; 95% CI, 1.91–7.63), age ≥45 years (HR (vs. age <45 years)=1.79; 95% CI, 1.03–3.11), female sex (HR=1.61; 95% CI, 1.04–2.49), and Hispanic race/ethnicity (HR (vs. white race)=2.81; 95% CI, 1.23–6.41). Presence/absence of a systemic inflammatory disease, laterality of uveitis, and smoking status were not associated with differential incidence. Conclusions Our results suggest that intermediate uveitis is a chronic disease with an overall low rate of remission. Recently diagnosed cases, and older, female and Hispanic cases were more likely to remit. With regards to management, pars plana vitrectomy was associated with increased probability of remission. PMID:26772874

  16. A comprehensive review and update on the biologic treatment of adult noninfectious uveitis: part II.

    PubMed

    Lee, Kyungmin; Bajwa, Asima; Freitas-Neto, Clovis A; Metzinger, Jamie Lynne; Wentworth, Bailey A; Foster, C Stephen

    2014-11-01

    Treatment of adult, noninfectious uveitis remains a major challenge for ophthalmologists around the world, especially in regard to recalcitrant cases. It is reported to comprise approximately 10% of preventable blindness in the USA. The cause of uveitis can be idiopathic or associated with infectious and systemic disorders. The era of biologic medical therapies provides new options for patients with otherwise treatment-resistant inflammatory eye disease. This two-part review gives a comprehensive overview of the existing medical treatment options for patients with adult, noninfectious uveitis, as well as important advances for the treatment ocular inflammation. Part I covers classic immunomodulation and latest information on corticosteroid therapy. In part II, emerging therapies are discussed, including biologic response modifiers, experimental treatments and ongoing clinical studies for uveitis. The hazard of chronic corticosteroid use in the treatment of adult, noninfectious uveitis is well documented. Corticosteroid-sparing therapies, which offer a very favorable risk-benefit profile when administered properly, should be substituted. Although nothing is currently approved for on-label use in this indication, many therapies, through either translation or novel basic science research, have the potential to fill the currently exposed gaps.

  17. Adalimumab for the treatment of refractory noninfectious paediatric uveitis.

    PubMed

    Muñoz-Gallego, Alicia; Barral, Estefanía; Enríquez, Eugenia; Tejada, Pilar; Barceló, Ana; de Inocencio, Jaime

    2017-06-01

    To report the experience of our center with the use of adalimumab (ADA) for the treatment of severe refractory noninfectious paediatric uveitis. The study is a retrospective case series of all paediatric patients with refractory uveitis who were treated with ADA at the Paediatric Uveitis Unit of our center from 2008 to 2015. We present 12 patients (6 Juvenile idiopathic arthritis-associated uveitis, 4 idiopathic panuveitis, 1 early-onset sarcoidosis-associated panuveitis, and 1 intermediate uveitis), with uveitis in 19/24 eyes. Once ADA therapy was started, all the patients presented improved activity according to Standardization of Uveitis Nomenclature (SUN) criteria. Nine out of the 12 patients had structural damage before ADA could be started: cataract (n = 4), glaucoma (n = 2), cystic macular edema (n = 1), exudative retinal detachment (n = 1), and optic disk edema (n = 5). Visual acuity improved or maintained stable in 17/19 affected eyes, and only 2 eyes decreased its visual acuity because of structural damage, which was already present before ADA therapy. In our experience, ADA presents a good safety profile and is efficacious in the treatment of paediatric patients with different forms of refractory noninfectious uveitis.

  18. Retinal imaging in uveitis

    PubMed Central

    Gupta, Vishali; Al-Dhibi, Hassan A.; Arevalo, J. Fernando

    2014-01-01

    Ancillary investigations are the backbone of uveitis workup for posterior segment inflammations. They help in establishing the differential diagnosis and making certain diagnosis by ruling out certain pathologies and are a useful aid in monitoring response to therapy during follow-up. These investigations include fundus photography including ultra wide field angiography, fundus autofluorescence imaging, fluorescein angiography, optical coherence tomography and multimodal imaging. This review aims to be an overview describing the role of these retinal investigations for posterior uveitis. PMID:24843301

  19. Elevated S100A8/A9 and S100A12 Serum Levels Reflect Intraocular Inflammation in Juvenile Idiopathic Arthritis-Associated Uveitis: Results From a Pilot Study.

    PubMed

    Walscheid, Karoline; Heiligenhaus, Arnd; Holzinger, Dirk; Roth, Johannes; Heinz, Carsten; Tappeiner, Christoph; Kasper, Maren; Foell, Dirk

    2015-12-01

    Juvenile idiopathic arthritis-associated uveitis (JIAU) is the most common uveitis entity in childhood. As S100A8/A9 and S100A12 proteins are valuable biomarkers in childhood arthritis, we investigated the occurrence of these proteins in childhood uveitis. Serum samples from patients with JIAU (n = 79) or idiopathic anterior uveitis (IAU, n = 24), as well as from nonuveitic controls (n = 24), were collected. Furthermore, aqueous humor samples (JIAU n = 17, nonuveitic controls n = 16, IAU n = 12) were obtained. Samples were analyzed for S100A8/A9 and S100A12 protein levels by ELISA. Intergroup comparisons were performed, involving patient data, clinical data, and S100 levels. S100A8/A9 and S100A12 serum levels were elevated in IAU and JIAU patients as compared to nonuveitic controls (all P < 0.05). S100 serum levels in JIAU patients were higher in active arthritis (not significant; P = 0.289 for S100A8/A9 and P = 0.196 for S100A12) and active uveitis (P = 0.010 for S100A8/A9 and P = 0.026 for S100A12) than in controls. No significant differences in S100 levels were found in a subgroup analysis for sex, antinuclear antibody (ANA) status, disease duration, or presence of uveitis complications. In JIAU patients, S100 serum levels correlated with age and age at onset of uveitis. A longitudinal analysis in JIAU patients showed a correlation of serum S100A8/A9 and S100A12 levels with uveitis activity (both P = 0.03). S100A8/A9 levels in aqueous humor of patients with JIAU (P = 0.001) and IAU (P = 0.0002) were increased as compared to nonuveitic controls. Increased S100A8/A9 and S100A12 levels are found in the serum and aqueous humor of patients with autoimmune uveitis. Serum levels reflect activity of joint and eye disease.

  20. Impact of Juvenile Idiopathic Arthritis Associated Uveitis in Early Adulthood

    PubMed Central

    Vernie, Lenneke A.; Rothova, Aniki; v. d. Doe, Patricia; Los, Leonoor I.; Schalij-Delfos, Nicoline E.; de Boer, Joke H.

    2016-01-01

    Background Typically juvenile idiopathic arthritis (JIA)-associated uveitis (further referred as ‘JIA-uveitis’) has its onset in childhood, but some patients suffer its, sometimes visual threatening, complications or ongoing disease activity in adulthood. The objective of this study was to analyze uveitis activity, complications and visual prognosis in adulthood. Methods In this multicenter study, 67 adult patients (129 affected eyes) with JIA-uveitis were retrospectively studied for best corrected visual acuity, visual fields, uveitis activity, topical/systemic treatments, ocular complications, and ocular surgeries during their 18th, 22nd and 30th year of life. Because treatment strategies changed after the year 1990, outcomes were stratified for onset of uveitis before and after 1990. Results Sixty-two of all 67 included patients (93%) had bilateral uveitis. During their 18th life year, 4/52 patients (8%) had complete remission, 28/52 (54%) had uveitis activity and 37/51 patients (73%) were on systemic immunomodulatory treatment. Bilateral visual impairment or legal blindness occurred in 2/51 patients (4%); unilateral visual impairment or legal blindness occurred in 17/51 patients (33%) aged 18 years. The visual prognosis appeared to be slightly better for patients with uveitis onset after the year 1990 (for uveitis onset before 1990 (n = 7) four patients (58%) and for uveitis onset after 1990 (n = 44) 13 patients (30%) were either visual impaired or blind). At least one ocular surgery was performed in 10/24 patients (42%) between their 18th and 22nd year of life. Conclusions Bilateral visual outcome in early adulthood in patients with JIA-uveitis appears to be fairly good, although one third of the patients developed one visually impaired or blind eye. However, a fair amount of the patients suffered from ongoing uveitis activity and needed ongoing treatment as well as surgical interventions. Awareness of these findings is important for ophthalmologists and

  1. SOCS3 Deletion in T-Lymphocytes Suppresses Development of Chronic Ocular Inflammation Via Up-regulation of CTLA-4 and Expansion of Regulatory T cells

    PubMed Central

    Yu, Cheng-Rong; Kim, Sung-Hye; Mahdi, Rashid M.; Egwuagu, Charles E.

    2013-01-01

    Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of JAK/STAT pathway and SOCS3 contributes to host immunity by regulating the intensity/duration of cytokine signals and inflammatory responses. Mice with Socs3 deletion in myeloid cells exhibit enhanced STAT3-signaling, expansion of Th1 and Th17 cells and developed severe experimental autoimmune encephalomyelitis (EAE). Interestingly, development of the unique IL-17/IFN-γ-double producing (Th17/IFN-γ and Tc17/IFN-γ) subsets that exhibit strong cytotoxic activities and associated with pathogenesis of several autoimmune diseases, has recently been shown to depend on epigenetic suppression of SOCS3 expression, further suggesting involvement of SOCS3 in autoimmunity and tumor immunity. In this study, we generated mice with Socs3 deletion in CD4 T cell compartment (CD4-SOCS3KO) to determine in vivo effects of the loss of Socs3 in the T cell-mediated autoimmune disease, experimental autoimmune uveitis (EAU). In contrast to the exacerbation of EAE in myeloid-specific SOCS3-deleted mice, CD4-SOCS3KO mice were protected from acute and chronic uveitis. Protection from EAU correlated with enhanced expression of CTLA4 and expansion of IL-10 producing Tregs with augmented suppressive activities. We further show that SOCS3 interacts with CTLA4 and negatively regulates CTLA4 levels in T cells, providing mechanistic explanation for the expansion of Tregs in CD4-SOCS3 during EAU. Contrary to in vitro epigenetic studies, Th17/IFN-γ and Tc17/IFN-γ populations were markedly reduced in CD4-SOCS3KO, suggesting that SOCS3 promotes expansion of Th17/IFN-γ subset associated with development of severe uveitis. Thus, SOCS3 is a potential therapeutic target in uveitis and other auto-inflammatory diseases. PMID:24101549

  2. Incidence and risk factors for chronic uveitis following cataract surgery.

    PubMed

    Patel, Chirag; Kim, Stephen Jae; Chomsky, Amy; Saboori, Mazeyar

    2013-04-01

    To determine the incidence of and associated risk factors for uveitis after cataract surgery. A total of 17,757 eyes were identified and records of 42 eyes that developed uveitis and 2320 eyes that did not were reviewed. Postsurgical uveitis was defined as persistent inflammation for ≥ 6 months after surgery. Forty-two eyes of 35 patients developed uveitis (0.24%). Eleven patients underwent consecutive cataract surgery but developed unilateral uveitis, and intraoperative complications occurred in 55% of uveitic eyes compared to 0% in fellow eyes (p < 0.05). Median duration of inflammation was 8 and 11.5 months in eyes with and without vitrectomy (p < 0.05). Intraocular complications occurred in 44 and 8.3% of eyes that did and did not develop uveitis, respectively (p = 0.01). Postsurgical uveitis developed after approximately 1 in 400 cataract surgeries and occurred more frequently in eyes experiencing intraoperative complications.

  3. A case of Sweet's syndrome associated with uveitis in a young male with ulcerative colitis.

    PubMed

    Bancu, Ligia Ariana; Ureche, Corina; Crăciun, Nicoleta Maria; Marian, Dorin

    2016-01-01

    Sweet's syndrome is rare acute febrile neutrophilic dermatosis whose onset is either idiopathic or associated with other underlying conditions, such as infections, autoimmune diseases, pregnancy, use of certain medications, or malignancy. We report the case of a young male with known history of ulcerative colitis and abrupt onset of high fever, malaise, blurred vision and eruption of painful erythematous nodules and papules, localized on the head, neck, trunk and upper limbs. Ophthalmological examination established the diagnosis of anterior uveitis. Inflammatory markers were positive. Histological examination of skin lesions revealed a dense neutrophilic infiltrate of the dermis. Clinical, laboratory and histological findings were suggestive for the diagnosis of Sweet's syndrome and uveitis on a background of ulcerative colitis. Systemic and ophthalmic administration of corticotherapy leads to a prompt resolution of symptoms and inflammatory syndrome. The particularity of this case is the occurrence of two simultaneous extraintestinal manifestations in a young male with inflammatory bowel disease and colonic involvement. Although a relatively rare condition, Sweet's syndrome should be considered as a differential diagnosis in patients with acute onset of high fever and skin rash, as it may have notable internal involvement and can be easily treated.

  4. HLA-B27 Anterior Uveitis: Immunology and Immunopathology.

    PubMed

    Wakefield, Denis; Yates, William; Amjadi, Shahriar; McCluskey, Peter

    2016-08-01

    Acute anterior uveitis (AAU) is the commonest type of uveitis and HLA-B27 AAU is the most frequently recognized type of acute anterior uveitis and anterior uveitis overall. Recent evidence indicates that acute anterior uveitis is a heterogenous disease, is polygenic and is frequently associated with the spondyloarthropathies (SpA). Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis. Recently described genetic associations cluster around immunologic pathways, including the IL-17 and IL-23 pathways, antigen processing and presentation, and lymphocyte development and activation. Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis. These observations have major implications for understanding the pathogenesis of HLA-B27 diseases, such as AAU, and may lead to the development of more specific therapy for AAU. Received 6 January 2016; revised 6 February 2016; accepted 18 February 2016; published online 31 May 2016.

  5. Pigment dispersion syndrome masquerading as acute anterior uveitis.

    PubMed

    Gonzalez-Gonzalez, Luis Alonso; Rodríguez-García, Alejandro; Foster, C Stephen

    2011-06-01

    Signs and symptoms of pigment dispersion may be confused with those of acute anterior uveitis. This case series is intended to aid the ophthalmologist in the clinical differentiation between these two disorders. The authors present a series of 6 patients with pigment dispersion who were initially diagnosed as having acute anterior uveitis and treated with anti-inflammatory medication, including corticosteroids. The patients were referred for a second opinion due to poor or no response to therapy and were found to have pigment dispersion instead of uveitis. Symptoms of pigment dispersion may consist of blurred vision, redness, ocular pain, and photophobia, all of which are also symptoms of acute anterior uveitis. These symptoms, plus the fact that pigment floating in the aqueous humor can be mistaken for inflammation, make diagnosis challenging. Moreover, the possible co-existence of true anterior uveitis and pigment dispersion makes the diagnosis and treatment more difficult.

  6. Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice

    USDA-ARS?s Scientific Manuscript database

    Autoimmune disease is prevalent in humans. Since conventional therapies have limited efficacy and often come with significant side effects, nutrition may provide an alternative and complementary approach to improving the autoimmune disorders. Naringenin, a flavonoid found in citrus fruits, has been ...

  7. Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

    PubMed Central

    Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

    2014-01-01

    Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds. PMID:24711694

  8. Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis.

    PubMed

    Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

    2014-01-01

    Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.

  9. IL-6 blockade in the management of non-infectious uveitis.

    PubMed

    Lopalco, Giuseppe; Fabiani, Claudia; Sota, Jurgen; Lucherini, Orso Maria; Tosi, Gian Marco; Frediani, Bruno; Iannone, Florenzo; Galeazzi, Mauro; Franceschini, Rossella; Rigante, Donato; Cantarini, Luca

    2017-07-01

    Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases. Interleukin (IL)-6 holds a critical role in the pathogenic pathways of uveitis, due to its extended and protean range of effects. On this background, manipulation of IL-6 inflammatory cascade has unraveled encouraging outcomes. For instance, rising evidence has been achieved regarding the successful use of tocilizumab, the humanized monoclonal antibody targeted against the IL-6 receptor, in treating uveitis related to juvenile idiopathic arthritis or Behçet's disease. Similar findings have also been reported for uveitis associated with systemic disorders, such as rheumatoid arthritis or multicentric Castleman disease, but also for idiopathic uveitis, the rare birdshot chorioretinopathy, and even in cases complicated by macular edema. This work provides a digest of all current experiences and evidences concerning IL-6 blockade, as suggested by the medical literature, proving its potential role in the management of non-infectious uveitis.

  10. The Eyes Have It: A Rheumatologist's View of Uveitis.

    PubMed

    Rosenbaum, James T; Dick, Andrew D

    2018-05-23

    Uveitis is defined as intraocular inflammation. It is an extra-articular manifestation of many forms of joint disease which include spondyloarthritis, juvenile idiopathic arthritis, and Behcet's disease. Rheumatologists may be asked to consult on patients with uveitis in order to identify an associated systemic illness. Diagnoses such as spndyloarthritis, sarcoidosis, and interstitial nephritis with uveitis are frequently overlooked by referring ophthalmologists. Alternatively rheumatologists may be asked to help manage the immunosuppression including biologics which can be required to treat a subset of patients with uveitis. This review is written to provide rheumatologists with the necessary information to facilitate collaboration in co-managing patients with uveitis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Listerial keratoconjunctivitis and uveitis (silage eye).

    PubMed

    Erdogan, Hidayet Metin

    2010-11-01

    Listerial keratoconjunctivitis or silage eye has increasingly been reported in ruminants in recent years. Although the disease has always been associated with silage feeding, its cause, pathogenesis, and epidemiology remain to be fully disclosed. Clinical courses include signs of keratoconjunctivitis and uveitis and cases recover without any residual lesions after antibiotic therapy. More epidemiologic and clinical as well as experimental studies are required to determine this poorly defined condition so that preventive measures could be established. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy

    NASA Astrophysics Data System (ADS)

    Li, Xingyi; Wang, Yuqin; Yang, Chengbiao; Shi, Shuai; Jin, Ling; Luo, Zichao; Yu, Jing; Zhang, Zhaoliang; Yang, Zhimou; Chen, Hao

    2014-11-01

    Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular compatibility in rats, as indicated by the optical coherence tomography (OCT) images, HE observation, and glial fibrillary acidic protein (GFAP) and vimentin immuno-staining assays of the retinas. Our TA hydrogel showed a decreased efficacy to inhibit ocular inflammation in the rat's experiment autoimmune uveitis (EAU) model compared to the commercial TA suspension (Transton®), but without causing complications such as high intraocular pressure and cataracts. These promising properties of the hydrogel indicated its great potential for the treatment of eye diseases.Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular

  13. Experimental autoimmune hearing loss

    PubMed Central

    Billings, Peter

    2004-01-01

    Understanding of autoimmune sensorineural hearing loss (ASNHL) has been hindered by the inaccessibility of the inner ear to biopsy and the lack of workable animal models. A report in this issue of the JCI describes a mouse model of CD4+ T cell–mediated ASNHL induced by immunization with peptides from the inner ear–specific proteins cochlin and β-tectorin. PMID:15085190

  14. Prevalence of Toxoplasma gondii and Toxocara canis among patients with uveitis.

    PubMed

    Lim, Su Jin; Lee, Sang Eun; Kim, Sun Hyun; Hong, Sung-Hee; You, Yong Sung; Kwon, Oh Woong; Kim, Hyeun Seung

    2014-10-01

    To investigate the prevalence of Toxoplasma gondii and Toxocara canis in patients with uveitis. Patients with uveitis were examined. Serum antibodies to T. gondii and T. canis were tested by using enzyme-linked immunosorbent assay (ELISA). Polymerase chain reaction (PCR) was done using blood and aqueous humor (AH). 98 patients were enrolled. Mean age was 43.5 ± 13.2 years. Six patients were seropositive for T. gondii with the following pattern-anterior uveitis: 1; posterior uveitis with retinitis: 2; pan uveitis: 2. One patient had a positive result of PCR for T.gondii in AH, who showed pan uveitis. 23 patients were positive to serum IgG for T. canis with the following clinical manifestation-granuloma: 6; pigmented scar: 3; virtrits: 6-but none were PCR positive. T.gondii and T.canis are still one of the important causes of uveitis. Ocular toxocariasis is not an uncommon cause of uveitis even in adult.

  15. [Diagnosis of herpetic uveitis and keratouveitis].

    PubMed

    Schacher, S; Garweg, J G; Russ, C; Böhnke, M

    1998-05-01

    In epithelial viral keratitis as in viral retinitis, the diagnosis is made on the basis of typical clinical findings. A laboratory confirmation is achieved in over 80% using routine laboratory methods. In contrast, it is almost impossible to confirm the diagnosis of stromal herpetic keratitis in vivo using the currently available laboratory methods. Nothing is known about the situation in cases of viral anterior uveitis. Of 52 patients with granulomatous anterior uveitis, 31 were diagnosed on the basis of clinical findings as active herpetic uveitis (group 1), 14 as active granulomatous uveitis of unknown origin (group 2), and 7 had inactive disease after quietening down of herpetic uveitis (group 3). From all patients, aqueous humor was collected at the time of diagnosis and processed for viral culture, Herpes antigen ELISA, and amplification of viral DNA of HSV-1 and VZV. Viral growth in culture was found in only one case in group 3. In this group, viral antigen or viral DNA were detected in no case. Herpes antigen was found in 5/31 cases (16%) in group 1 and in 1/11 cases (9%) in group 2, and viral DNA was found in 8/31 cases from group 1 (5x HSV-1 and 3x VZV) and in 5/14 cases (31%) from group 2. After combination of antigen detection and DNA amplification, the presence of virus was confirmed in 14/45 cases (29%). Virus culture has not proven useful in the diagnosis of viral anterior segment disease. Despite their high overall sensitivity, neither antigen ELISA nor the amplification of viral DNA proved sensitive enough to establish a viral etiology. Nevertheless, a laboratory confirmation should be attempted in granulomatous uveitis of unknown origin after preclusion of an underlying systemic disease because of the consequences of a diagnosis of viral anterior segment disease for treatment and prognosis.

  16. Burden and direct costs of non infectious uveitis in Spain.

    PubMed

    Adán-Civera, Alfredo Manuel; Benítez-Del-Castillo, José Manuel; Blanco-Alonso, Ricardo; Pato-Cour, Esperanza; Sellas-Fernández, Agustí; Bañares-Cañizares, Antonio

    2016-01-01

    There is no updated information on epidemiology and cost of management of non infectious uveitis (NIU) in Spain. This study assessed the frequency of various types of uveítis as well as associated costs of resources used in their management. NIU epidemiological data and direct costs were collected from a literature search. This was complemented with consensus information from 2 expert panel meetings and data from questionnaires to ophthalmologists and rheumatologists, experts on these conditions. Healthcare resources costs were obtained from the Oblikue database, from a medical society and from approved drug prices in Spain. During 2011 the estimate number of NIU was 9,398 (45% male, 70% aged 16-65 years). Incidence per type of uveitis was: acute anterior uveitis (AAU) 55%; posterior uveitis (PU) and pan-uveitis (PanU) 15% each; adult chronic anterior uveitis, paediatric chronic anterior uveitis and intermediate uveitis 5% each. Among total costs (77,834,282.10€), initial drug therapy was the highest (43,602,359.29€), followed by surgical treatment of complications (8,367,420.43€). With respect to types of uveitis, PanU (26,692,948.29€), PU (22,283,330.50€) and AAU (14,336,755.38€) showed the highest associated costs. Non infectious uveitis is associated to high costs in Spain, both in its diagnosis and in its treatment. Early diagnosis and treatment should allow for substantial savings for the National Health System. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  17. Pattern of uveitis in a university-based referral center in southern Thailand.

    PubMed

    Sittivarakul, Wantanee; Bhurayanontachai, Patama; Ratanasukon, Mansing

    2013-01-01

    To identify the characteristics (demographics, anatomical classification, diagnoses, and treatment) of all uveitis patients who were seen at our newly started Uveitis and Ocular Inflammatory Disease Clinic over a two-year period. The computerized uveitis database files and medical records for all new consecutive patients seen at our Uveitis and Ocular Inflammatory Disease Clinic from January 2010 through December 2011 were included. A total of 254 patients were seen during the study period. Anterior uveitis and panuveitis were most frequently found, each accounting for around 35% of cases. Specific diagnoses were established in 70.9% of patients and the top five most common specific diagnoses were VKH (11%), HLA-B27-associated anterior uveitis (7.9%), Behçet disease (7.1%), toxoplasmosis (7.1%), and herpetic anterior uveitis (4.7%). In this setting, the authors found VKH to be the most common diagnosis in the noninfectious uveitis group. Regarding infectious uveitis, toxoplasmosis ranked the most common diagnosis.

  18. Uveitis profile and treatment response in Iranian patients with sarcoidosis.

    PubMed

    Mahmoudzadeh, Pouya; Tousi, Adib; Ramezani, Alireza; Soheilian, Roham; Soheilian, Masoud

    2015-06-01

    The aim of the study was to assess the clinical features and treatment responses in Iranian patients with sarcoid uveitis. A retrospective review of patients diagnosed with sarcoid uveitis from 1996 to 2010 was performed in a referral clinic in Tehran, Iran. Demographic and clinical features of patients, treatment modalities and therapeutic responses, and outcomes were recorded. Sixty-six eyes from 36 patients were studied. Twenty cases had biopsy-proven sarcoidosis. Mean duration of follow-up was 44.7 ± 45 months (range 3-175). Thirty-six eyes (54.5 %) had intermediate uveitis, 25 (37.9 %) panuveitis, and 5 (7.6 %) anterior uveitis. Twenty patients (55.5 %) responded to both systemic and/or topical corticosteroids, and 16 (44.4 %) required immunomodulatory drugs for control of uveitis. All of the patients finally responded to treatment in the form of inflammation reduction and/or vision improvement. The average time interval before initial clinical response following treatment was 3.2 ± 3 months (range 1-72). This study disclosed a higher predominance of females and intermediate form of uveitis in Iranian patients with sarcoid uveitis. Use of immunomodulatory drugs combined with corticosteroids resulted in good visual outcome and control of uveitis with a possible fewer corticosteroid side effects.

  19. Treatment strategies for childhood noninfectious chronic uveitis: an update.

    PubMed

    Cantarini, Luca; Simonini, Gabriele; Frediani, Bruno; Pagnini, Ilaria; Galeazzi, Mauro; Cimaz, Rolando

    2012-01-01

    Uveitis is an inflammatory disorder involving inflammation of the uveal tract. It is classified as anterior, intermediate, posterior or panuveitis, depending on the part of eye affected by the inflammatory process. In children, noninfectious, chronic uveitis is a relatively uncommon but serious disease, with the potential for significant long-term complications and possible blindness. Although frequently associated with an underlying systemic disease, for example, juvenile idiopathic arthritis, a significant number of cases in children show no associated signs or symptoms and are labeled as idiopathic. We reviewed the available literature. Taking into account this evidence, an anti-inflammatory therapy based on an immunomodulatory approach seems a reasonable strategy for noninfectious chronic uveitis, in children as well as in adults. Due to a lack of controlled studies regarding uveitis in children, immunosuppressive strategy is supported only at evidence level III. Our aim is to review the currently available medical strategies for the treatment of childhood sight-threatening chronic uveitis. Uveitis in children can be severe. Methotrexate is the drug of choice for recalcitrant cases, and biologic therapies can be useful in selected situations.

  20. Presumed tuberculous uveitis in non-endemic country for tuberculosis: case series from a New Zealand tertiary uveitis clinic.

    PubMed

    Ng, Ken K; Nisbet, Mitzi; Damato, Erika M; Sims, Joanne L

    2017-05-01

    To describe the clinical spectrum of presumed tuberculous (TB) uveitis in a developed, non-endemic country of high immigrant population. Retrospective review of a consecutive case series. All 39 patients diagnosed with presumed TB uveitis at the tertiary uveitis service in Auckland from 2007 to 2014. Clinical chart review. Patient demographics, risk factors, ophthalmic manifestations, management and outcome. The median age was 37 years (interquartile range [IQR] 31-52) and 56% were female. The majority (97%) were born outside of New Zealand, and 77% had no TB-related history. Radiological abnormalities consistent with TB were evident in seven patients, including three who had culture positive pulmonary disease. Anterior uveitis was diagnosed in ten patients (26%), anterior and intermediate uveitis in eight (21%), posterior uveitis in 13 (33%) and panuveitis in eight (21%). Sixteen (41%) had retinal vasculitis, and five (13%) had multifocal serpiginoid choroiditis. Common complications included cataract (51%), ocular hypertension (36%), broad posterior synechiae (33%) and cystoid macular oedema (28%). Anti-TB treatment was initiated in 30 patients (76%). All but three patients completed the intended course of six to 12 months. Following anti-TB treatment, 67% remained in remission for at least 12 months, and all but two patients successfully stopped systemic steroids. The median initial and final visual acuity was 6/9 (IQR 6/6-6/18) and 6/6 (IQR 6/6-6/9), respectively. Despite a wide range of ocular presentations and complications, our cohort demonstrated good remission rate and visual prognosis following anti-TB treatment in carefully selected patients. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

  1. Bilateral Herpes Simplex Uveitis: Review of the Literature and Own Reports‏.

    PubMed

    de-la-Torre, Alejandra; Valdes-Camacho, Juanita; Foster, C Stephen

    2017-08-01

    Herpes simplex-associated uveitis is usually considered a unilateral eye disease, and rarely included in the differential diagnosis whenever there is bilateral involvement. We report three cases of bilateral herpetic anterior uveitis. We evaluated three patients who presented with clinical manifestations of bilateral uveitis suggestive of viral origin. We found intraocular hypertension, cells in the anterior chamber, paralytic mydriasis, iris atrophy with transillumination defects, and variable anterior vitreous cellularity. According to the clinical findings, supported with herpes-specific antibody titers and aqueous humor PCR results in two of them, they were diagnosed with bilateral anterior herpetic uveitis. Our patients were initially misdiagnosed as having non-infectious uveitis and were treated with immunomodulatory medications, which could have favored the extension of infection bilaterally. Although uncommon, bilateral herpetic uveitis should always be considered in the differential diagnoses, when patients present with hypertensive uveitis in both eyes.

  2. Clinical and investigative profile of biopsy-proven sarcoid uveitis in India.

    PubMed

    Ganesh, Sudha K; Agarwal, Manisha

    2008-01-01

    Retrospective analysis of the clinical features, investigative profile, response to treatment, and final visual outcome in histopathologically confirmed cases of sarcoid uveitis. Retrospective case series analysis was done of 15 eyes of 9 patients seen between July 1999 and August 2003 with biopsy-proven sarcoid uveitis. There were 3 were males and 6 females. The mean age at presentation was 44.1 years (range 11-62 years), The mean follow-up was 28.4 months. Six patients had bilateral ocular involvement and 3 had unilateral involvement. Five out of 9 patients had primarily ocular involvement. The most common presentation was intermediate uveitis and granulomatous anterior uveitis in 7 patients. Eight of 9 patients responded well to the medical treatment with systemic and periocular steroids. Ocular lesions can be the primary manifestation of systemic sarcoidosis. Sarcoid uveitis in the Asian Indian population often presents an intermediate uveitis with granulomatous anterior uveitis.

  3. Cyclooxygenase-2 expression in the eyes of cats with and without uveitis.

    PubMed

    Sim, Zhi Hui; Pinard, Chantale L; Plattner, Brandon L; Bienzle, Dorothee

    2018-01-01

    OBJECTIVE To characterize the distribution and intensity of cyclooxygenase (COX)-2 expression in the eyes of cats with and without uveitis and to determine whether COX-2 expression is correlated with severity of inflammation. SAMPLES Archived ocular tissue specimens from 51 cats with and 10 cats without ocular disease. PROCEDURES Specimens from only 1 eye were evaluated for each cat. Specimens were stained with H&E stain or immunohistochemical stain for detection of COX-2 and reviewed. For each eye, the type, severity, and distribution of inflammation and the distribution and intensity of COX-2 expression were determined for the uvea and other ocular tissues. Correlation between COX-2 expression and inflammation severity was also assessed. RESULTS COX-2 was not expressed in any nondiseased eye. Of the 51 diseased eyes, 20 had histologic evidence of lymphocytic-plasmacytic uveitis, 13 had neutrophilic uveitis, 11 had diffuse iris melanoma with uveitis, and 7 had diffuse iris melanoma without uveitis. Of the 44 eyes with uveitis, COX-2 was detected in the uvea of 16, including 11 eyes with lymphocytic-plasmacytic uveitis, 4 with neutrophilic uveitis, and 1 with diffuse iris melanoma-induced uveitis. Inflammation was severe, moderate, or mild in 10, 5, and 1 of those eyes, respectively. Cyclooxygenase-2 was detected in the cornea of 21 eyes with uveitis and 1 eye with diffuse iris melanoma without uveitis. Uveitis severity was positively correlated with COX-2 expression in both the uvea and cornea. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that COX-2 is an inflammatory mediator in feline uveitis but not diffuse iris melanoma.

  4. Uveitis in Children: Diagnosis and Management.

    PubMed

    Gupta, Anju; Ramanan, A V

    2016-01-01

    Uveitis is a term used to describe inflammation of uvea, which is the middle layer of eye. It is an important cause of blindness in children in both developed and developing countries. Delayed diagnosis, inadequate treatment and risk of amblyopia are some of the factors that are unique to childhood uveitis and are responsible for significant morbidity seen with this disease.

  5. Adalimumab for the treatment of uveitis.

    PubMed

    LaMattina, Kara C; Goldstein, Debra A

    2017-03-01

    Adalimumab, an inhibitor of tumor necrosis factor-alpha (TNFα), is the only systemic non-corticosteroid agent which has been approved by the US Food and Drug Administration (FDA) for the treatment of non-infectious uveitis. Areas covered: The aim of this review is to summarize the research which demonstrated the effectiveness of adalimumab in the treatment of intraocular inflammation and helped to establish its side effect profile, ultimately leading to its FDA approval. Expert commentary: Adalimumab is a useful second-line agent in the treatment of non-infectious uveitis. While it is only approved in the United States for use in intermediate, posterior, and panuveitis in adults, I find it to be effective in off-label treatment of pediatric uveitis and scleritis as well.

  6. Hsp70 Regulates Immune Response in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Mansilla, M. José; Costa, Carme; Eixarch, Herena; Tepavcevic, Vanja; Castillo, Mireia; Martin, Roland; Lubetzki, Catherine; Aigrot, Marie-Stéphane; Montalban, Xavier; Espejo, Carmen

    2014-01-01

    Heat shock protein (Hsp)70 is one of the most important stress-inducible proteins. Intracellular Hsp70 not only mediates chaperone-cytoprotective functions but can also block multiple steps in the apoptosis pathway. In addition, Hsp70 is actively released into the extracellular milieu, thereby promoting innate and adaptive immune responses. Thus, Hsp70 may be a critical molecule in multiple sclerosis (MS) pathogenesis and a potential target in this disease due to its immunological and cytoprotective functions. To investigate the role of Hsp70 in MS pathogenesis, we examined its immune and cytoprotective roles using both in vitro and in vivo experimental procedures. We found that Hsp70.1-deficient mice were more resistant to developing experimental autoimmune encephalomyelitis (EAE) compared with their wild-type (WT) littermates, suggesting that Hsp70.1 plays a critical role in promoting an effective myelin oligodendrocyte glycoprotein (MOG)-specific T cell response. Conversely, Hsp70.1-deficient mice that developed EAE showed an increased level of autoreactive T cells to achieve the same production of cytokines compared with the WT mice. Although a neuroprotective role of HSP70 has been suggested, Hsp70.1-deficient mice that developed EAE did not exhibit increased demyelination compared with the control mice. Accordingly, Hsp70 deficiency did not influence the vulnerability to apoptosis of oligodendrocyte precursor cells (OPCs) in culture. Thus, the immunological role of Hsp70 may be relevant in EAE, and specific therapies down-regulating Hsp70 expression may be a promising approach to reduce the early autoimmune response in MS patients. PMID:25153885

  7. A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia

    PubMed Central

    Na, Songqing; Ma, Yanfei; Zhao, Jingyong; Schmidt, Clint; Zeng, Qing Q.; Chandrasekhar, Srinivasan; Chin, William W.; Nagpal, Sunil

    2011-01-01

    Vitamin D receptor (VDR) agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH)2D3 and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM) compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activity in vivo than 1,25-(OH)2D3. Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia. PMID:21318047

  8. Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine.

    PubMed

    Bhat, Roopa; Mahapatra, Sidharth; Axtell, Robert C; Steinman, Lawrence

    2017-12-15

    In patients with multiple sclerosis, the selective serotonin reuptake inhibitor, fluoxetine, resulted in less acute disease activity. We tested the immune modulating effects of fluoxetine in a mouse model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE). We show that fluoxetine delayed the onset of disease and reduced clinical paralysis in mice with established disease. Fluoxetine had abrogating effects on proliferation of immune cells and inflammatory cytokine production by both antigen-presenting cells and T cells. Specifically, in CD 4 T cells, fluoxetine increased Fas-induced apoptosis. We conclude that fluoxetine possesses immune-modulating effects resulting in the amelioration of symptoms in EAE. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Management of Uveitis in Spondyloarthropathy: Current Trends

    PubMed Central

    Gupta, Nikhil; Agarwal, Aditi

    2018-01-01

    Spondyloarthritis is a chronic inflammatory disease predominantly affecting joints of the axial skeleton. However, as many as 50% of patients with this disease may have extra-articular manifestations, which include uveitis; psoriasis; inflammatory bowel disease such as Crohn disease or ulcerative colitis; cardiovascular manifestations in the form of conduction abnormalities, atherosclerosis, or valvular heart disease; pulmonary involvement; and rarely renal involvement. Uveitis occurs in 25% to 40% of patients with spondyloarthritis. Management of uveitis is crucial to prevent morbidity caused by vision loss and secondary complications. Treatment ranges from local therapies to systemic drugs and varies depending on the severity and response to treatment. Categories of medical treatment include nonsteroidal anti-inflammatory agents, corticosteroids, and steroid-sparing agents. Biologic therapies such as antitumor necrosis factor agents act early in the disease process and have revolutionized the field of rheumatology, including management of uveitis. This review will focus on the management of ophthalmic manifestations in spondyloarthropathies. PMID:29272246

  10. Prevalence of Toxoplasma gondii and Toxocara canis among Patients with Uveitis.

    PubMed

    Lim, Su Jin; Lee, Sang Eun; Kim, Sun Hyun; Hong, Sung-Hee; You, Yong Sung; Kwon, Oh Woong; Kim, Hyeun Seung

    2015-04-01

    To investigate the prevalence of Toxoplasma gondii and Toxocara canis in patients with uveitis. Patients with uveitis were examined. Serum antibodies to T. gondii and T. canis were tested by using the enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) was done using blood and aqueous humor (AH). Ninety-eight patients were enrolled. Mean age was 43.5 ± 13.2 years. Six patients were seropositive for T. gondii with the following pattern: anterior uveitis, 1; posterior uveitis with retinitis, 2; pan uveitis, 2. One patient had a positive PCR result for T. gondii in AH, who showed panuveitis. Twenty-three patients were positive to serum IgG for T. canis with the following clinical manifestation: granuloma, 6; pigmented scar, 3; vitritis, 6--but none were PCR positive. T. gondii and T. canis are still important causes of uveitis. Ocular toxocariasis is not an uncommon cause of uveitis, even in adults.

  11. Incidence and prevalence of uveitis in South Korea: a nationwide cohort study.

    PubMed

    Rim, Tyler Hyungtaek; Kim, Sung Soo; Ham, Don-Il; Yu, Seung-Young; Chung, Eun Jee; Lee, Sung Chul

    2018-01-01

    To evaluate the incidence and prevalence of uveitis and associated risk factors in South Korea. For this retrospective national cohort study, approximately 1 000 000 Korean residents were randomly selected from the Korean National Health Insurance Service database. Uveitis was defined according to the Korean Classification of Diseases. The uveitis incidence and prevalence were calculated. Sociodemographic factors and comorbidities associated with uveitis were evaluated via Cox proportional regression models. A total of 1 094 440 subjects were evaluated over 7 051 346 person-years (mean follow-up: 6.44 years). Overall, 7447 newly developed uveitis cases were identified during the period of 2007-2013; the average incidence of uveitis was 10.6 per 10 000 person-years (95% CI 10.3 to 10.8). The average incidences of anterior and non-anterior uveitis were 9.0 and 1.5 per 10 000 person-years, respectively. The prevalence rates of uveitis, anterior uveitis and non-anterior uveitis were 17.3, 15.0 and 2.3 per 10 000 persons, respectively, during the period of 2007-2013. Increasing age, male sex, residing in a relatively rural area and high income were associated with uveitis, along with Behçet's disease, juvenile idiopathic arthritis, ankylosing spondylitis, systemic lupus erythematous, ulcerative colitis and tuberculosis. The overall incidence of uveitis in Korea was similar to those reported in Taiwan and the USA. Despite a potentially inaccurate disease definition, claims data may be useful for monitoring the substantial uveitis burden in South Korea. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. TAM receptor knockout mice are susceptible to retinal autoimmune induction.

    PubMed

    Ye, Fei; Li, Qiutang; Ke, Yan; Lu, Qingjun; Han, Lixia; Kaplan, Henry J; Shao, Hui; Lu, Qingxian

    2011-06-16

    TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU). TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology. Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina. Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.

  13. Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

    PubMed

    Pryce, Gareth; Riddall, Dieter R; Selwood, David L; Giovannoni, Gavin; Baker, David

    2015-06-01

    Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system. Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms. However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease. Although there is limited evidence that the cannabinoids from cannabis are having significant immunosuppressive activities that will influence relapsing autoimmunity, we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability. Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels. In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans. Although a 3 year, phase III clinical trial did not detect a beneficial effect of oral Δ9-THC in progressive MS, a planned subgroup analysis of people with less disability who progressed more rapidly, demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo. Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.

  14. Characteristics of childhood uveitis leading to visual impairment and blindness in the Netherlands.

    PubMed

    Hettinga, Ymkje M; Verhagen, Fleurieke H; van Genderen, Maria; de Boer, Joke H

    2014-12-01

    To investigate the clinical characteristics of childhood uveitis leading to visual impairment or blindness. In this descriptive study, we reviewed data from the medical records of 58 children with visual impairment or blindness due to childhood uveitis, which were seen at an institute for visually impaired patients (Bartiméus) between January 1981 and December 2012, in a retrospective, cross-sectional manner. Thirty-two of the 58 children (55%) were visually impaired and 26 (45%) were legally blind. Uveitis was posterior in 76% of all cases. Infectious uveitis represented 74% of all cases, of which 86% was congenital. Five patients (9%) had uveitis related to a systemic disease, and ten patients (17%) had idiopathic uveitis. There was a decrease in infectious causes over the last decades (p = 0.04) and an increase in idiopathic uveitis (p < 0.01), but the rate of children with posterior uveitis remained constant. There was an overall decrease in the number of children with uveitis referred to Bartiméus. The number of ocular complications at the time of intake was higher in children with acquired disease compared with congenital diseases (p < 0.01), as it was in children with non-infectious uveitis compared with infectious uveitis (p = 0.04). Most comorbidities that were noted were seen in children with infectious uveitis. Most patients suffering from visual impairment or blindness due to childhood uveitis had posterior and/or infectious uveitis, mostly congenital. There is a shift in causes which shows a decrease in infectious causes and an increase in idiopathic causes. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. New Immunosuppressive Therapies in Uveitis Treatment

    PubMed Central

    Mérida, Salvador; Palacios, Elena; Navea, Amparo; Bosch-Morell, Francisco

    2015-01-01

    Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines. PMID:26270662

  16. Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

    PubMed

    Oray, Merih; Tuğal-Tutkun, İlknur

    2016-04-01

    Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA)-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

  17. Epidemiology of uveitis among the Chinese population in Taiwan: a population-based study.

    PubMed

    Hwang, De-Kuang; Chou, Yiing-Jeng; Pu, Cheng-Yun; Chou, Pesus

    2012-11-01

    This study aimed to investigate the incidence and prevalence of uveitis in Taiwan, and then analyzed the risk factors related to uveitis using multivariate regression. Population-based cohort study using medical claims data. We randomly selected 1 000 000 residents from the Taiwan National Health Insurance Research Database. All participants with correct registry data (96%) were included in the study. The study period was from 2000 to 2008. All types of uveitis were identified using the International Classification of Diseases, 9th revision, Clinical Modification diagnostic codes. The annual incidence and cumulative prevalence of uveitis were calculated. A univariate and a multivariate Poisson regression were used to determine the risk factors associated with uveitis. The first diagnosis of uveitis noted during the study period. The annual cumulative incidence rate of uveitis ranged from 102.2 to 122.0 cases per 100 000 persons over the study period, and the average incidence density was 111.3 cases per 100 000 person-years (95% confidence interval, 108.4-114.1). The cumulative prevalence was found to have increased from 318.8 cases per 100 000 persons in 2003 to 622.7 cases per 100 000 persons in 2008. Anterior uveitis was the most common location and accounted for 77.7% of all incident cases, which was followed by panuveitis, posterior uveitis, and intermediate uveitis. Multivariate regression analysis showed that males, the elderly, and individuals who lived in an urban area had higher incidence rates for uveitis. The epidemiology of uveitis in Taiwan differs from most previous studies in other countries. The incidence of uveitis in Taiwan has increased significantly recently. The elderly and individuals living in urban areas are the populations that are most commonly affected by uveitis. These findings are consistent with suggestions found in several recent studies. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights

  18. Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices.

    PubMed

    Zhao, Chan; Zhang, Meifen

    2017-04-10

    Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and

  19. Pediatric uveitis.

    PubMed

    Patel, Hemang; Goldstein, Debra

    2003-02-01

    Uveitis in children is an entity most pediatricians and ophthalmologists seldom encounter. It is prevalent in society, however, and the high incidence of sight-threatening complications in untreated children warrants a baseline knowl-edge of the diseases and disorders involved as well as a sense of when to refer to a specialist.

  20. Human leukocyte antigen B27 and B51 double-positive Behçet uveitis.

    PubMed

    Ahn, Jae Kyoun; Park, Yeoung Geol

    2007-10-01

    To describe the clinical characteristics of human leukocyte antigen (HLA) B27 and B51 double-positive Behçet uveitis and to determine whether the coexistence of HLA-B27 can affect Behçet uveitis. We retrospectively reviewed the medical records of patients with Behçet uveitis and patients with HLA-B27-associated non-Behçet uveitis who underwent HLA-B27 and HLA-B51 typing and were followed up for more than 3 years. We divided the patients into 3 groups according to HLA-B27/B51 status and compared the clinical outcomes. Main outcome measures were demographic features, uveitis characteristics, complications, treatments, and visual prognosis. Fourteen patients with HLA-B27(+)B51(+) Behçet uveitis, 43 patients with HLA-B27(-)B51(+) Behçet uveitis, and 41 patients with HLA-B27(+)B51(-) non-Behçet uveitis were identified. HLA-B27(+)B51(+) Behçet uveitis showed the demographic features similar to HLA-B27(-) counterparts. However, HLA-B27(+)B51(+) Behçet uveitis showed less involvement of posterior segments, a less chronic course, fewer complications in posterior segments, and less use of systemic medication or surgical intervention for inflammatory control, similar to HLA-B27(+)B51(-) non-Behçet uveitis. The long-term vision prognosis of HLA-B27(+)B51(+) Behçet uveitis was more favorable than that of HLA-B27(-)B51(+) Behçet uveitis. Our results indicate that HLA-B27(+)B51(+) Behçet uveitis is a benign subgroup of Behçet uveitis. The positivity of HLA-B27 may be a good prognostic factor in Behçet uveitis.

  1. Experimental uveitis can be maintained in rabbits for a period of six weeks after a safe sensitization method.

    PubMed

    Eperon, S; Balaskas, K; Vaudaux, J; Guex-Crosier, Y

    2013-03-01

    New treatments against long-lasting uveitis need to be tested. Our aim was to develop a six-week model of uveitis in rabbits. Rabbits were presensitized with an s.c. injection of Mycobacterium tuberculosis H37RA emulsified with TiterMax Gold adjuvant. Uveitis was induced at day 28 and 50, by intravitreal challenges of antigen suspension. Ocular inflammation was assessed till euthanasia at day 71 after s.c. injection of M. tuberculosis H37RA by: (a) the number of inflammatory cells in aqueous humor (AH); (b) the protein concentration in AH; (c) the clinical score (mean of conjunctival hyperaemia, conjunctival chemosis, oedema and secretion); (d) the microscopical score (mean presence of fibrin and synechiae, aqueous cell density and aqueous flare grade, as scored by slit lamp). At the sites of presensitization injection, rabbits presented flat nodules which progressively vanished. The first challenge induced a significant increase in the four parameters (p < 0.05 the Wilcoxon/Kruskal-Wallis test). The AH contained 764 ± 82 cells/µl and 32 ± 0.77 mg protein/ml. During the following days, inflammatory parameters decreased slightly. The second intravitreal challenge increased inflammation (3564 ± 228 cells/µl AH and 31 ± 1 mg protein/ml), which remained at a high level for a longer period of time. We developed a model of long-term uveitis, which could be maintained in rabbits for at least six weeks. Such a model could be used to test the efficacy of either new drugs or various drug delivery systems intended to deliver active agents during a few months.

  2. The efficacy of intravitreal interferon alpha-2b for the treatment of experimental endotoxin-induced uveitis.

    PubMed

    Afarid, Mehrdad; Lashkarizadeh, Hamid; Ashraf, Mohammad J; Nowroozzadeh, Mohammad Hossein; Shafiee, Sayed M

    2016-05-01

    To study the efficacy of intravitreal interferon alpha-2b for endotoxin-induced uveitis. A total of 36 rabbits were randomly allocated to one of the three groups: (1) received interferon plus balanced-salt solution; (2) received lipopolysaccharide (LPS) plus interferon; and (3) received LPS plus balanced-salt solution. Intraocular inflammation was evaluated by slit-lamp biomicroscopy (standardization of uveitis nomenclature grading), binocular indirect ophthalmoscopy (BIO) score, and histopathology. Group 2 showed significantly lower mean (±standard deviation) anterior chamber reaction than Group 3 (3.1 ± 0.9 vs. 3.8 ± 0.4) on day 1 postinjection, lower vitreous cells on days 1 through 7 (day 1: 3.1 ± 0.9 vs. 3.8 ± 0.4; day 3: 2.1 ± 1.6 vs. 3.8 ± 0.4; day 7: 1.9 ± 1.3 vs. 3.6 ± 0.7), and lower BIO score on days 1-7 (day 1: 3.3 ± 1.2 vs. 4.4 ± 0.7; day 3: 3.0 ± 1.4 vs. 4.3 ± 0.9; day 7: 2.4 ± 1.4 vs. 3.7 ± 1.2). The protein content of anterior and vitreous aspirates was lower in Group 2 than 3 (1618.5 ± 411.4 vs. 2567.3 ± 330.8 and 2157.0 ± 283.3 vs. 3204.6 ± 259.5, respectively). Intravitreal interferon alpha-2b was effective in controlling endotoxin-induced uveitis.

  3. Prophylactic Effect of Probiotics on the Development of Experimental Autoimmune Myasthenia Gravis

    PubMed Central

    Chae, Chang-Suk; Kwon, Ho-Keun; Hwang, Ji-Sun; Kim, Jung-Eun; Im, Sin-Hyeog

    2012-01-01

    Probiotics are live bacteria that confer health benefits to the host physiology. Although protective role of probiotics have been reported in diverse diseases, no information is available whether probiotics can modulate neuromuscular immune disorders. We have recently demonstrated that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental disorders in mice model. In this study we further investigated whether IRT5 probiotics could modulate the progression of experimental autoimmune myasthenia gravis (EAMG). Myasthenia gravis (MG) is a T cell dependent antibody mediated autoimmune disorder in which acetylcholine receptor (AChR) at the neuromuscular junction is the major auto-antigen. Oral administration of IRT5 probiotics significantly reduced clinical symptoms of EAMG such as weight loss, body trembling and grip strength. Prophylactic effect of IRT5 probiotics on EMAG is mediated by down-regulation of effector function of AChR-reactive T cells and B cells. Administration of IRT5 probiotics decreased AChR-reactive lymphocyte proliferation, anti-AChR reactive IgG levels and inflammatory cytokine levels such as IFN-γ, TNF-α, IL-6 and IL-17. Down-regulation of inflammatory mediators in AChR-reactive lymphocytes by IRT5 probiotics is mediated by the generation of regulatory dendritic cells (rDCs) that express increased levels of IL-10, TGF-β, arginase 1 and aldh1a2. Furthermore, DCs isolated from IRT5 probiotics-fed group effectively converted CD4+ T cells into CD4+Foxp3+ regulatory T cells compared with control DCs. Our data suggest that IRT5 probiotics could be applicable to modulate antibody mediated autoimmune diseases including myasthenia gravis. PMID:23284891

  4. Mononuclear cell secretome protects from experimental autoimmune myocarditis.

    PubMed

    Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

    2015-03-14

    Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

  5. Mononuclear cell secretome protects from experimental autoimmune myocarditis

    PubMed Central

    Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

    2015-01-01

    Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. PMID:23321350

  6. Equine uveitis: a UK perspective.

    PubMed

    Lowe, R C

    2010-03-01

    Uveitis in the equine population of the UK does not appear to be as prevalent or disastrous as seen across regions of Europe and the USA. Some cases perceived to be recurrent uveitis may be poorly resolved single episodes of uveitis and care should be taken not to make the diagnosis of recurrence without ensuring effective control of the initial episode. Leptospira spp. appear to play only a minor role ERU in the UK which is probably the main reason for the prevalence of the disease being much lower compared to the USA and mainland Europe. Actual data are relatively few on the ground as far as disease surveillance in concerned. This has 2 implications. Firstly unless we are able to effectively monitor the levels of uveitic disease, it will be difficult to pick up early changes in the trend which may allow quicker intervention. Secondly, it is difficult to secure funding for further research if the prevalence of the problem is poorly defined. This may leave the UK equine population at risk should the disease profile suddenly alter for the worse.

  7. Benefits of Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, and Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.

    PubMed

    Kempen, John H; Altaweel, Michael M; Drye, Lea T; Holbrook, Janet T; Jabs, Douglas A; Sugar, Elizabeth A; Thorne, Jennifer E

    2015-10-01

    To compare the benefits of fluocinolone acetonide implant therapy versus systemic corticosteroid therapy supplemented (when indicated) with immunosuppression for intermediate uveitis, posterior uveitis, and panuveitis. Additional follow-up of a randomized comparative effectiveness trial cohort. Two hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis randomized to implant or systemic therapy. Best-corrected visual acuity (BCVA), visual field mean deviation (MD), activity of uveitis, and presence of macular edema (per reading center grading) ascertained prospectively. Trial participants were followed-up for 54 months from original randomization. The visual function trajectory in uveitic eyes demonstrated a similar (P = 0.73) degree of modest (not statistically significant) improvement from baseline to 54 months in both groups (mean improvement in BCVA at 54 months, 2.4 and 3.1 letters in the implant and systemic groups, respectively). Many had excellent initial visual acuity, limiting the potential for improvement. The mean automated perimetry MD score remained similar to baseline throughout 48 months of follow-up in both groups. Overall control of inflammation was superior in the implant group at every time point assessed (P < 0.016), although most eyes in the systemic therapy arm also showed substantial improvement, achieving complete control or low levels of inflammation. Although macular edema improved significantly more often with implant treatment within the first 6 months, the systemic group gradually improved over time such that the proportions with macular edema converged in the 2 groups by 36 months and overlapped thereafter (P = 0.41 at 48 months). Visual outcomes of fluocinolone acetonide implant and systemic treatment for intermediate uveitis, posterior uveitis, and panuveitis were similarly favorable through 54 months. The implant maintained a clear advantage in controlling inflammation through 54 months. Nevertheless

  8. Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

    PubMed Central

    Hunter, Rebecca S; Lobo, Ann-Marie

    2011-01-01

    Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

  9. Uveitis in spondyloarthritis including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease.

    PubMed

    Rosenbaum, James T

    2015-06-01

    Uveitis is a common complication of spondyloarthritis. The "phenotype" of the uveitis characteristic of ankylosing spondylitis (sudden onset, anterior, unilateral, recurrent, more often male) may differ from the phenotype often seen with either psoriatic arthritis or inflammatory bowel disease (insidious onset, anterior and intermediate, bilateral, chronic, and/or more often female). The frequency of uveitis is also much greater in association with ankylosing spondylitis than with either inflammatory bowel disease or psoriasis. Uveitis may affect the choice of therapy and can rarely be a complication of therapy. Uveitis and arthritis also co-exist in several animal models.

  10. The future of uveitis treatment.

    PubMed

    Lin, Phoebe; Suhler, Eric B; Rosenbaum, James T

    2014-01-01

    Uveitis is a heterogeneous collection of diseases with polygenic and environmental influences. This heterogeneity presents challenges in trial design and selection of end points. Despite the multitude of causes, therapeutics targeting common inflammatory pathways are effective in treating diverse forms of uveitis. These treatments, including corticosteroids and immunomodulatory agents, although often effective, can have untoward side effects, limiting their utility. The search for drugs with equal or improved efficacy that are safe is therefore paramount. A mechanism-based approach is most likely to yield the future breakthroughs in the treatment of uveitis. We review the literature and provide examples of the nuances of immune regulation and dysregulation that can be targeted for therapeutic benefit. As our understanding of the causes of uveitis grows we will learn how to better apply antibodies designed to block interaction between inflammatory cytokines and their receptors. T-lymphocyte activation can be targeted by blocking co-stimulatory pathways or inhibiting major histocompatibility complex protein interactions. Furthermore, intracellular downstream molecules from cytokine or other pathways can be inhibited using small molecule inhibitors, which have the benefit of being orally bioavailable. An emerging field is the lipid-mediated inflammatory and regulatory pathways. Alternatively, anti-inflammatory cytokines can be provided by administering recombinant protein, and intracellular "brakes" of inflammatory pathways can be introduced potentially by gene therapy. Novel approaches of delivering a therapeutic substance include, but are not limited to, the use of small interfering RNA, viral and nonviral gene therapy, and microparticle or viscous gel sustained-release drug-delivery platforms. Copyright © 2014. Published by Elsevier Inc.

  11. Assessment of diagnostic and therapeutic vitrectomy for vitreous opacity associated with uveitis with various etiologies

    PubMed Central

    Sato, Tomohito; Kinoshita, Rina; Taguchi, Manzo; Sugita, Sunao; Kaburaki, Toshikatsu; Sakurai, Yutaka; Takeuchi, Masaru

    2018-01-01

    Abstract Vitreous opacity (VO) is a common feature of intermediate uveitis, posterior uveitis, and panuveitis. Fundus observation is critical for determining the etiology of uveitis, however, is often interfered with VO. In these clinical settings, vitrectomy contributes to a correct diagnosis and guides alternative management strategies. The purpose of this study was to evaluate the diagnostic yield and surgical outcome of vitrectomy in uveitic patients with VO and compare the visual outcome between infectious and noninfectious uveitis. Forty-five eyes with uveitis-associated VO underwent diagnostic and therapeutic vitrectomy, and etiological diagnosis of uveitis was confirmed in 34 of 45 eyes (75.6%). The diagnoses were infectious uveitis in 13 eyes (28.9%), noninfectious uveitis in 21 eyes (46.7%), and unidentified uveitis in 11 eyes (24.4%). Visual acuity (VA) improvement rates at 6 months after surgery were 69.2%, 76.2%, and 90.9% in the infectious, noninfectious, and unidentified uveitis groups, with no significant difference among 3 groups. Significant decrease in inflammation score after vitrectomy was observed only in the infectious uveitis group. This study demonstrated that diagnostic vitrectomy for inflammatory eyes with VO of unknown etiology was effective in infectious and noninfectious uveitis, and the therapeutic effect of VA improvement was observed in both types of uveitis. PMID:29480837

  12. HL-A27 and anterior uveitis.

    PubMed

    Woodrow, J C; Mapstone, R; Anderson, J; Usher, N

    1975-09-01

    HL-A types were determined in 90 successive patients with non-granulomatous uveitis. Fifty-one were HL-A27 positive (55.7%) compared to 8.2% of controls. Of 16 patients with ankylosing spondylitis, 13 were HL-A27 positive, as were two patients with a history of Reiter's syndrome. Twenty-eight patients were HL-A27 positive but had no evidence of rheumatic disease. The findings are discussed in relation to the possible pathogenesis of uveitis.

  13. Targeting interleukin-6 for noninfectious uveitis

    PubMed Central

    Lin, Phoebe

    2015-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine implicated in the pathogenesis of many immune-mediated disorders including several types of non-infectious uveitis. These uveitic conditions include Vogt-Koyanagi-Harada syndrome, uveitis associated with Behçet disease, and sarcoidosis. This review summarizes the role of IL-6 in immunity, highlighting its effect on Th17, Th1, and plasmablast differentiation. It reviews the downstream mediators activated in the process of IL-6 binding to its receptor complex. This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab. The target, dosage, potential side effects, and potential uses of these biologics are summarized in this article based on the existing literature. In summary, anti-IL-6 therapy for non-infectious uveitis shows promise in terms of efficacy and side effect profile. PMID:26392750

  14. Readability Assessment of Online Uveitis Patient Education Materials.

    PubMed

    Ayoub, Samantha; Tsui, Edmund; Mohammed, Taariq; Tseng, Joseph

    2017-12-29

    To evaluate the readability of online uveitis patient education materials. A Google search in November 2016 was completed using search term "uveitis" and "uveitis inflammation." The top 50 websites with patient-centered information were selected and analyzed for readability using the Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Gunning FOG Index (GFI), and Simple Measure of Gobbledygook (SMOG). Statistical analysis was performed with two-tailed t-tests. The mean word count of the top 50 websites was 1162.7 words, and averaged 16.2 words per sentence. For these websites, the mean FRES was 38.0 (range 4-66, SD = 12.0), mean FKGL was 12.3 (range 6.8-19, SD = 2.4), mean SMOG score was 14.4 (range 9.8-19, SD = 1.8), and the mean Gunning FOG index was 14.0 (range 8.6-19, SD = 2.0). The majority of online patient directed uveitis materials are at a higher reading level than that of the average American adult.

  15. Plumbagin suppresses dendritic cell functions and alleviates experimental autoimmune encephalomyelitis.

    PubMed

    Zhang, Kai; Ge, Zhenzhen; Da, Yurong; Wang, Dong; Liu, Ying; Xue, Zhenyi; Li, Yan; Li, Wen; Zhang, Lijuan; Wang, Huafeng; Zhang, Huan; Peng, Meiyu; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

    2014-08-15

    Plumbagin (PL, 5-hydroxy-2-methyl-1,4-naphthoquinone) is a herbal compound derived from medicinal plants of the Droseraceae, Plumbaginaceae, Dioncophyllaceae, and Ancistrocladaceae families. Reports have shown that PL exerts immunomodulatory activity and may be a novel drug candidate for immune-related disease therapy. However, its effects on dendritic cells (DCs), the most potent antigen-presenting cells (APCs), remain unclear. In this study, we demonstrate that PL inhibits the differentiation, maturation, and function of human monocyte-derived DCs. PL can also restrict the expression of Th1- and Th17-polarizing cytokines in mDC. In addition, PL suppresses DCs both in vitro and in vivo, as demonstrated by its effects on the mouse DC line DC2.4 and mice with experimental autoimmune encephalomyelitis (EAE), respectively. Notably, PL ameliorated the clinical symptoms of EAE, including central nervous system (CNS) inflammation and demyelination. Our results demonstrate the immune suppressive and anti-inflammatory properties of PL via its effects on DCs and suggest that PL could be a potential treatment for DC-related autoimmune and inflammatory diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. [The clinical investigation of peripheral retinal changes of anterior uveitis].

    PubMed

    Guo, Chunying; Qiao, Lijun; Yang, Liu

    2015-10-01

    To observe the peripheral retinal changes of anterior uveitis patients using ultra-wide field fluorescein angiography. Retrospective case series study. Thirty-three eyes of 20 patients diagnosed as anterior uveitis from September to November 2013 in the ophthalmic clinic of Peking University First Hospital was included. All the patients underwent routine ocular examination, followed by ultra-wide field Fluorescein. There were 13 male patients and 7 female patients, aged 23-66, an average of 46 years old. The anterior uveitis recurrent in both eyes in 13 patients and only one eye in 7 patients. Uveitis duration ranging from months to 30 years. Twenty eyes were at the active stage of the anterior uveitis while 13 eyes in the quiescent stage. Peripheral retinal vessels leakage was detected in 57.6% (19/33) of the eyes, among which in eyes with active disease the rate of peripheral retinal vessels leakage was 75% (15/20), and in eyes with quiescent disease the rate was 30.8% (4/13). Optic disk hyperfluorescence was found in 6 of 20 eyes with active disease. Cystoid macular edema was found in 4 eyes. In addition, peripheral retinal hyperfluorescence dot and zone were detected in 2 eyes. Peripheral retinal vessels were detected to have inflammative leakage in patients of anterior uveitis by ultra-wide field fluorescein agiography. Peripheral retinal inflammation may still exist even in the quiescent stage of the anterior uveitis.

  17. Profile of patients with uveitis referred to a multidisciplinary unit in northern Spain.

    PubMed

    Fanlo, P; Heras, H; Pérez, D; Tiberio, G; Espinosa, G; Adan, A

    2017-05-01

    To describe the main characteristics of a cohort of patients with uveitis referred to a multidisciplinary unit in northern Spain. Retrospective analysis of clinical records of patients evaluated in the Multidisciplinary Unit of the Navarra Hospital Complex from the period January 2010 until March 2015. An analysis was performed on the demographic characteristics, origin, types of uveitis, laterality, and aetiology. The present series was also compared with 2 previous series from Castilla y León and Barcelona. A total of 500 patients were identified, with a mean age of 47.9±16.4 years, with 50% women. The most frequent type of uveitis was anterior uveitis (65.4%), followed by posterior uveitis (17.6%), panuveitis (15.2%), and intermediate uveitis (1.8%). The origin was unclassifiable in 31.2%, followed by non-infectious systemic disease in 29.2%. Ankylosing spondylitis was the most frequent cause in 10.8% of patients, followed by herpes infection in 9.2%, and toxoplasmosis in 7.8%, respectively. Compared with the 2other cohorts, the present cohort showed a higher proportion of unilateral anterior uveitis. Furthermore, the patients from the Navarra series had a higher prevalence of unilateral and idiopathic uveitis compared to the series from Barcelona. The main characteristics of the present cohort of patients with uveitis are similar to those of patients from other regions of our country. Unilateral anterior uveitis and idiopathic uveitis were the most frequent in our series. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Association of leptospiral seroreactivity and breed with uveitis and blindness in horses: 372 cases (1986-1993).

    PubMed

    Dwyer, A E; Crockett, R S; Kalsow, C M

    1995-11-15

    Recurrent uveitis, a leading cause of blindness in horses, often develops as a sequela to systemic leptospirosis. Over a 7-year period, 63 of 112 (56%) horses with uveitis were seropositive for Leptospira interrogans serovar pomona, but only 23 of 260 (9%) horses without uveitis were seropositive. Odds-ratio analysis revealed that seropositive horses were 13.2 times more likely to have uveitis than were seronegative horses. Of the 63 seropositive horses with uveitis, 59% developed blindness, compared with only 24% in the 49 seronegative horses with uveitis that lost vision in 1 or both eyes during the same period. Odds-ratio analysis revealed that seropositive horses with uveitis were 4.4 times more likely to lose vision than were seronegative horses with uveitis. Of the 112 horses with uveitis, 28 (25%) were Appaloosas, compared with only 10 of the 260 (4%) horses without uveitis (odds ratio, 8.3). In addition, 19 of the 28 (68%) Appaloosas with uveitis developed blindness, compared with only 30 of the 84 (36%) non-Appaloosas with uveitis that lost vision in 1 or both eyes (odds ratio, 3.8). This field study therefore confirmed a strong positive relationship between uveitis and leptospiral seroreactivity in horses. Furthermore, the data suggested that seropositive horses with uveitis were at increased risk of losing vision, compared with that in seronegative horses with uveitis, and that Appaloosas were at increased risk of developing uveitis and associated blindness, compared with that in non-Appaloosas.

  19. Cytokines, chemokines and soluble adhesion molecules in aqueous humor of children with uveitis.

    PubMed

    Sijssens, Karen M; Rijkers, Ger T; Rothova, Aniki; Stilma, Jan S; Schellekens, Peter A W J F; de Boer, Joke H

    2007-10-01

    Uveitis in childhood is a visual threatening disease with a complication rate of more than 75%. Despite extensive research, the etiology of uveitis is still unclear although the general opinion is now that uveitis is a T-cell mediated disease. The purpose of this study was to investigate the profile of cytokines, chemotactic cytokines (chemokines) and soluble adhesion molecules in the aqueous humor (AqH) of children with uveitis in order to identify the factors that control the immune response in the eye. In this clinical laboratory investigation we analyzed, with a multiplex immunoassay, 16 immune mediators in the AqH of 25 children with uveitis and 6 children without uveitis. Increased levels of interleukin-2 (IL-2), IL-6, IL-10, IL-13, IL-18, interferon-gamma, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, RANTES, IL-8 and interferon-inducible 10-kDa protein were found in the AqH of children with uveitis compared with controls. No significant differences were found for IL-1 beta, IL-4, IL-12 p-70, soluble vascular cell adhesion molecule 1 and Eotaxin. Lower levels of IL-10 and IL-8 were found in quiet stage uveitis (surgical) samples compared with active uveitis (diagnostic) samples and in samples of patients treated with methotrexate (MTX) compared with samples of patients not treated with MTX. Lower levels of IL-10 were as well found in samples taken during the first 3 months after the diagnosis of uveitis than samples taken later during the disease process. No significant differences were found between patients treated with or without topical or systemic (perioperative and long term) corticosteroids. In conclusion, in children with uveitis, multiple intraocular cytokines, chemokines and soluble adhesion molecules are increased in the AqH regardless of active or inactive inflammation. Whether the IL-8 and IL-10 levels in AqH of children with uveitis are correlated with uveitis activity, early or late phase of the course of the disease

  20. Equine recurrent uveitis: the viewpoint from the USA.

    PubMed

    Gilger, B C

    2010-03-01

    Equine recurrent uveitis (ERU) is a common disease in horses in the USA. There have been many advances in the treatment of ERU; however, frequent misdiagnosis of ERU occurs in cases of primary corneal or uveal disease. It is critical to remember that primary uveitis (i.e. one bout of inflammation) is a different disease to ERU, which is an immune mediated recurrent uveitis. Standard symptomatic anti-inflammatory therapy is effective to control most cases of ERU; however, some horses require advanced therapy, such as placement of drug delivery devices or removal of the vitreous, when they fail to respond to the standard therapy.

  1. Response of Pediatric Uveitis to Tumor Necrosis Factor-α Inhibitors

    PubMed Central

    Lerman, Melissa A.; Burnham, Jon M.; Chang, Peter Y.; Daniel, Ebenezer; Foster, C. Stephen; Hennessy, Sean; Jabs, Douglas A.; Joffe, Marshall M.; Kaçmaz, R. Oktay; Levy-Clarke, Grace A.; Mills, Monte D.; Nussenblatt, Robert B.; Rosenbaum, James T.; Suhler, Eric B.; Thorne, Jennifer E.; Kempen, John H.

    2013-01-01

    Objectives To evaluate the outcome of TNF-alpha inhibition (anti-TNFα) for pediatric uveitis. Methods We retrospectively assessed children (≤18 years) with non-infectious uveitis receiving anti-TNFα at five uveitis centers and one pediatric-rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at ≥2 consecutive ophthalmological exams ≥28 days apart while taking no oral and ≤2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses. Results Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% confidence interval [95% CI]: 62–87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI: 51–76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype amongst JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75–80% lower rate of achieving quiescence under anti-TNFα - independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis re-activated within 12 months of achieving quiescence in 14% of those continuing anti-TNFα (95% CI: 6–31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI: 1–43%). Conclusion Treatment with anti-TNFα was successful and sustained in a majority of children with non-infectious uveitis and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNFα. PMID:23818712

  2. Unimpaired Autoreactive T-Cell Traffic Within the Central Nervous System During Tumor Necrosis Factor Receptor-Mediated inhibition of Experimental Autoimmune Encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Korner, Heinrich; Goodsall, Anna L.; Lemckert, Frances A.; Scallon, Bernard J.; Ghrayeb, John; Ford, Andrew L.; Sedgwick, Jonathon D.

    1995-11-01

    The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin α, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4^+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin α in autoimmune tissue damage.

  3. Management of cataract in uveitis patients.

    PubMed

    Conway, Mandi D; Stern, Ethan; Enfield, David B; Peyman, Gholam A

    2018-01-01

    This review is timely because the outcomes of surgical invention in uveitic eyes with cataract can be optimized with adherence to strict anti-inflammatory principles. All eyes should be free of any cell/ flare for a minimum of 3 months preoperatively. Another helpful maneuver is to place dexamethasone in the infusion fluid or triamcinolone intracamerally at the end of surgery. Recent reports about the choice of intraocular lens material or lens design are germane to the best surgical outcome. Integrating these findings will promote better visual outcomes and allow advancement in research to further refine these surgical interventions in high-risk uveitic eyes. Control of inflammation has been shown to greatly improve postoperative outcomes in patients with uveitis. Despite better outcomes, more scientific research needs to be done regarding lens placement and materials and further research needs to adhere to the standardized reporting of uveitis nomenclature. Future studies should improve postoperative outcomes in eyes with uveitis so that they approach those of eyes undergoing routine cataract procedures.

  4. Uveitis in the elderly: epidemiological data from the National Long-term Care Survey Medicare Cohort.

    PubMed

    Reeves, Sherman W; Sloan, Frank A; Lee, Paul P; Jaffe, Glenn J

    2006-02-01

    There is a paucity of population-based data on the epidemiology of uveitis in the elderly. In the past 40 years, only 2 U.S. population-based studies have examined the epidemiology of uveitis. The conclusions of these studies on the burden of uveitis in the elderly differ greatly. In this analysis, we use Medicare claims data to define the population-based incidence and prevalence of uveitis in the United States elderly population. Cohort study. A cohort of 21644 Medicare beneficiaries drawn for the National Long-term Care Survey, a random sample of U.S. adults 65 years and older, was followed up from 1991 through 1999. The International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes specific to uveitis were queried. To decrease the inclusion of uveitis caused by surgery, diagnoses occurring within 3 months of intraocular surgery were excluded. The incidence and prevalence of uveitis by anatomic location was calculated for each year in the study. The onset of uveitis during a given year and its presence in subsequent years. The cumulative yearly incidence of uveitis ranged from 302/100000 to 424/100000 persons per year and averaged 340.9/100000 persons per year. Anterior uveitis was the most common form of uveitis in this population, with a mean incidence of 243.6 cases per 100000 persons per year. The incidence of posterior uveitis averaged 76.6/100000 and the incidence of panuveitis/endophthalmitis averaged 41.7/100000. Only 2 cases of intermediate uveitis occurred during the study period. The cumulative prevalence of uveitis doubled from 511/100000 in 1991 to 1231/100000 in 1999, with anterior uveitis accounting for most prevalent cases in every year. The burden of uveitis in the elderly is substantial and is higher than previously thought. Longitudinal analysis of Medicare claims data may provide a useful tool for monitoring uncommon diseases, such as uveitis, in the elderly population.

  5. Successful treatment of syphilitic uveitis in HIV-positive patients.

    PubMed

    Nurfahzura, Mohd-Jamil; Hanizasurana, Hashim; Zunaina, Embong; Adil, Hussein

    2013-01-01

    We report successful treatment of syphilitic uveitis in a case series of three Human immunodeficiency virus (HIV)-positive patients at Malaysia's Selayang Hospital eye clinic. All three patients with syphilitic uveitis were male, aged from 23 to 35 years old, with a history of high-risk behaviors. Of the patients, two presented with blurring of vision and only one patient presented with floaters in the affected eye. Ocular examination revealed intermediate uveitis (case 1 and case 3) and panuveitis (case 2). Each patient showed a high Venereal Disease Research Laboratory (VDRL) titer at presentation and they were also newly diagnosed as HIV positive with variable CD4 counts. All three patients responded well to a neurosyphilis regimen of intravenous penicillin G. At 3 months posttreatment, there was reduction in VDRL titer with improvement of vision in the affected eye. Diagnosis of syphilis needs to be ruled out in all cases of uveitis. All syphilitic uveitis cases should have HIV screening and vice versa, as syphilis is one of the most common infectious diseases associated with HIV-positive patients. Early detection and treatment are important for a good visual outcome.

  6. The spectrum of presumed tubercular uveitis in Tunisia, North Africa.

    PubMed

    Khochtali, Sana; Gargouri, Salma; Abroug, Nesrine; Ksiaa, Imen; Attia, Sonia; Sellami, Dorra; Feki, Jamel; Khairallah, Moncef

    2015-10-01

    The purpose of this study was to analyze the spectrum of presumed tubercular uveitis in Tunisia, North Africa. We retrospectively reviewed the clinical records of 38 patients (65 eyes) diagnosed with presumed tubercular uveitis at two referral centers in Tunisia, between January 2009 and December 2011. Mean age at presentation was 42.7 years. Twenty-four patients were women (63.2%) and 14 (36.8%) were men. Twenty-three eyes (35.4%) had posterior uveitis, 21 eyes (32.3%) had intermediate uveitis, 13 eyes (20%) had panuveitis, and 8 eyes (12.3%) had anterior uveitis. Ocular findings included vitritis in 67.7% of eyes, posterior synechiae in 47.7%, multifocal non-serpiginoid choroiditis in 23.1%, multifocal serpiginoid choroiditis in 21.5%, periphlebitis in 21.5%, and mutton-fat keratic precipitates in 20%. Anti-tubercular treatment was prescribed in 33 patients (86.8%) and was associated with systemic corticosteroids in 20 patients (52.6%) and periocular injections of corticosteroids in four patients (10.5%). After a mean follow-up of 14.2 months (range, 10-58), inflammation was controlled, with a significant improvement in visual acuity (VA) (p = 0.028). However, recurrences developed in two patients (5.3%). Final VA was better than 20/40 in 27 eyes (41.5%) and less than 20/200 in five eyes (7.7%). In Tunisia, all anatomic types are possible in tuberculosis-associated uveitis, but posterior and intermediate uveitis are more frequent. Vitritis, posterior synechiae, multifocal serpiginoid or non-serpiginoid choroiditis, and periphlebitis are the most common manifestations.

  7. The effects of Helicobacter pylori infection on intraocular pressure in anterior uveitis

    PubMed Central

    Kim, J M; Park, K H; Choi, M J; Ha, M M; Sohn, Y H; Kim, H K; Caprioli, J

    2012-01-01

    Purpose We investigated the influence of H. pylori infection on intraocular pressure (IOP) in anterior uveitis patients to clarify whether H. pylori infection is related to high IOP in anterior uveitis. Methods In this prospective study, 165 Korean anterior uveitis patients were examined. All patients underwent serological analysis to identify the cause of uveitis, including the presence of H. pylori infection by enzyme-linked immunosorbent assay. Serological values were compared between patients with and without high IOP. Results Seropositivity for H. pylori was 69.70% of patients with high IOP and 38.38% of patients with normal IOP (P<0.01). Conclusion This study suggests that H. pylori infection is associated with high IOP in anterior uveitis. PMID:23154495

  8. [Amblyopia and uveitis in childhood].

    PubMed

    Eckstein, A; Robering, A; Rudolph, G; Esser, J

    2007-06-01

    Manifestations of uveitis in the sensitive period of childhood can cause amblyopia. In most of the cases band keratopathy, dense cataracts and cyclitic membranes cause deprivation amblyopia. Asymmetrical damage can result in relative amblyopia. Secondary squint can lead to suppression amblyopia. For these reasons every visit during uveitis treatment should be accompanied by a search for amblyogenic factors and visual acuity measurements. In the case of a side difference in the visual acuity, occlusion therapy should be started. The follow-up should not only contain visual acuity measurements but also cycloplegic refraction. Especially when pupil-dilating drugs are necessary for a longer period, bifocals should be prescribed.

  9. Bilateral uveitis and Usher syndrome: a case report.

    PubMed

    Benson, Matthew D; MacDonald, Ian M

    2015-03-15

    Usher syndrome is a genetically heterogeneous condition and represents the most common cause of inherited combined vision and hearing loss. Deficits manifest as sensorineural hearing loss that typically develops at a young age and retinitis pigmentosa that can lead to peripheral vision loss and night blindness. As a result, this syndrome can have a significant impact on a patient's quality of life. Previous studies have described an association between Usher syndrome and Fuchs' heterochromic iridocyclitis, a form of non-granulomatous uveitis that generally presents in a unilateral manner. We present a rare finding of bilateral uveitis and, to the best of our knowledge, the first report of granulomatous uveitis as a feature in a patient with Usher syndrome. A 45-year-old Caucasian woman with a known history of retinitis pigmentosa presented to our clinic with suspected Usher syndrome, given her report of long-standing hearing loss. Aside from a mild loss in visual acuity, our patient was otherwise asymptomatic. Visual field testing, audiology and electroretinography findings supported the diagnosis of Usher syndrome. With slit lamp examination she was found to have bilateral keratic precipitates, with large, greasy-white, mutton-fat keratic precipitates on the endothelial surface of her left eye. A thorough work-up that included blood tests and imaging was negative for an alternative cause of her uveitis. We present a rare finding of bilateral uveitis and what we believe to be the first reported instance of mutton-fat keratic precipitates and granulomatous uveitis as a feature in a patient with Usher syndrome. By identifying atypical presentations of the disease, we hope to contribute to the range of ophthalmic conditions that may be seen in association with Usher syndrome.

  10. Updates on the risk markers and outcomes of severe juvenile idiopathic arthritis-associated uveitis

    PubMed Central

    Angeles-Han, Sheila T; Yeh, Steven; Vogler, Larry B

    2013-01-01

    Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis, which is the most common systemic cause of uveitis in children. Known risk factors for uveitis include antinuclear antibody seropositivity, young age of arthritis onset, specific juvenile idiopathic arthritis subtype and short duration of disease. Risk markers for severe ocular disease include gender, age and complications at initial visit. Due to the risk for vision-compromising sequelae such as cataracts, band keratopathy, glaucoma, vision loss and blindness, an understanding of the risk factors for uveitis development and severe ocular disease is crucial to help prevent serious visual disability and complications. This paper reviews the pathogenesis of uveitis, known risk factors for uveitis development and severe visual outcome, and addresses the need for additional biomarkers of uveitis risk, prognosis and remission. PMID:24187594

  11. Incidence and outcomes of uveitis in juvenile rheumatoid arthritis, a synthesis of the literature.

    PubMed

    Carvounis, Petros E; Herman, David C; Cha, Stephen; Burke, James P

    2006-03-01

    Juvenile rheumatoid arthritis (JRA) is the most common systemic cause of pediatric uveitis in Europe and North America. Uveitis is commonly perceived as a frequent sequela of JRA and JRA-associated uveitis is commonly considered to have a complicated course with frequent adverse visual outcomes. We performed a systematic literature search for series of consecutive patients with JRA (as defined by the American College of Rheumatology criteria) reporting on the frequency of uveitis and/or complications of uveitis, published between January 1980 and December 2004. The main outcome measures were: the cumulative incidence of uveitis in JRA, the cumulative incidence of adverse visual outcome and that of complications in JRA-associated uveitis. Additionally, the influence of gender, presence of antinuclear antibody (ANA) and disease onset subtype to the likelihood of developing uveitis were examined. Analysis of pooled data from the 26 eligible series suggested a cumulative incidence of uveitis in JRA of 8.3% [95% confidence intervals (CI), 7.5-9.1%]. The cumulative incidence of uveitis varied according to geographic location, being highest in Scandinavia, then the US, then Asia and lowest in India. JRA-associated uveitis was more common in pauciarticular than polyarticular onset patients [odds ratio (OR) = 3.2, 95% CI, 2.33-4.36] and in ANA-positive than ANA-negative patients (OR = 3.18, 95% CI, 2.22-4.54). Female gender was only a weak risk factor for the development of uveitis in JRA patients (OR = 1.69, 95% CI 1.09-2.62) and was not statistically significant after considering disease onset subtypes. In JRA-associated uveitis the cumulative incidence of cumulative incidence of adverse outcome (visual acuity < 20/40 OU) was 9.2% (95% CI: 4.7-15.8) of cataracts 20.5% (95% CI: 15.5-26.3), of glaucoma 18.9% (95% CI: 14.4-24.2) and of band keratopathy 15.7% (95% CI: 10.9-21.7). The cumulative incidence of uveitis in JRA varies according to geographic location, presence of

  12. Treatment and prevention of experimental autoimmune myocarditis with CD28 superagonists.

    PubMed

    Wang, Shu; Liu, Jing; Wang, Min; Zhang, Jinghui; Wang, Zhaohui

    2010-01-01

    Experimental autoimmune myocarditis (EAM), a rodent model of human dilated cardiomyopathy (DCM), is mediated by an autoimmune mechanism. We investigated whether a CD28 superagonistic antibody selectively targeting CD4+CD25+ regulatory T cells (T(regs)) provides effective therapy for EAM. Four groups of 5 rats were used. The normal control group was immunized with PBS. The EAM group was immunized with porcine myosin. The experimental group was immunized with myosin and superagonistic CD28 antibody JJ316. The final group was immunized with myosin and an unrelated rat IgG. Autoantibody and IL-10 production, CD4+CD25+ cell levels, Foxp3 expression and cardiac histology were analyzed. Anti-myosin autoantibody levels were higher in the EAM and isotype control groups than the normal control group (p < 0.05), and reduced in the CD28-JJ316 group (p < 0.05). The levels of CD25+CD4+ cells, IL-10 and splenocyte Foxp3 expression were significantly lower in the EAM and isotype control groups versus the CD28-JJ316 group (p < 0.05). Infiltration of inflammatory cells was observed in the EAM and isotype control groups, whereas CD28-JJ316 ameliorated myocarditis. CD28 superagonists could be effective in EAM treatment by up-regulating Foxp3 expression and contributing to CD4+CD25+ T(reg) activation and expansion. The enhancement in IL-10 by CD28 superagonists also ameliorated the disease.

  13. Uveitis and Juvenile Psoriatic Arthritis or Psoriasis.

    PubMed

    Salek, Sherveen S; Pradeep, Archana; Guly, Catherine; Ramanan, Athimalaipet V; Rosenbaum, James T

    2018-01-01

    To describe the phenotype of the uveitis that accompanies juvenile psoriatic arthritis or psoriasis. Observational case series. Setting: Two university-based referral clinics: 1 in England, 1 in the United States. Five children with uveitis and psoriatic arthritis and 1 with uveitis and psoriasis Observational Procedure: Retrospective chart review. Demographics of subjects such as age and sex; description of ocular and joint disease; surgical and other complications; medical treatment. Five of the 6 children in this series had the onset of disease at or before age 6 (P = .0008 compared to expected age of onset for psoriatic arthritis in childhood). All children in this series had an inadequate response to topical corticosteroids. Most of the children were treated with systemic corticosteroids for many months, yet all of them went on to require methotrexate. Therapy with systemic methotrexate did not suffice, as all the patients also required some form of biologic therapy. Five of 6 had surgeries such as vitrectomy, cataract extraction, or a procedure for glaucoma control. The observations suggest that the uveitis that accompanies juvenile psoriatic arthritis might be a distinct disease that is particularly severe when its onset affects children aged 6 years or younger. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. LruA and LruB Antibodies in Sera of Humans with Leptospiral Uveitis▿

    PubMed Central

    Verma, Ashutosh; Rathinam, S. R.; Priya, C. Gowri; Muthukkaruppan, V. R.; Stevenson, Brian; Timoney, John F.

    2008-01-01

    Uveitis can be a serious complication of leptospirosis. Previous studies indicated that the leptospiral lipoproteins LruA and LruB are expressed in the eyes of uveitic horses and that antibodies directed against those proteins show in vitro cross-reactivity with components of equine lens, ciliary body, and/or retina. We now demonstrate that sera from a significant proportion of humans who have leptospiral uveitis also contain antibodies against LruA and LruB. Different categories of nonleptospiral uveitis and autoimmune uveitis were also screened; patients diagnosed with Fuchs uveitis or Behçet's syndrome produced antibodies that cross-reacted with LruA and LruB, suggesting similarities of the autoimmune responses in those diseases with those of leptospiral uveitis. PMID:18400972

  15. Activation of the Stimulator of Interferon Genes (STING) adaptor attenuates experimental autoimmune encephalitis

    PubMed Central

    Lemos, Henrique; Huang, Lei; Chandler, Phillip R.; Mohamed, Eslam; Souza, Guilherme R.; Li, Lingqian; Pacholczyk, Gabriela; Barber, Glen N.; Hayakawa, Yoshihiro; Munn, David H.; Mellor, Andrew L.

    2014-01-01

    Cytosolic DNA sensing activates the Stimulator of Interferon Genes (STING) adaptor to induce interferon type I (IFNαβ) production. Constitutive DNA sensing to induce sustained STING activation incites tolerance breakdown leading to autoimmunity. Here we show that systemic treatments with DNA nanoparticles (DNPs) induced potent immune regulatory responses via STING signaling that suppressed experimental autoimmune encephalitis (EAE) when administered to mice after immunization with myelin oligodendrocyte glycoprotein (MOG), at EAE onset, or at peak disease severity. DNP treatments attenuated infiltration of effector T cells into the central nervous system (CNS) and suppressed innate and adaptive immune responses to MOG immunization in spleen. Therapeutic responses were not observed in mice treated with cargo DNA or cationic polymers alone, indicating that DNP uptake and cargo DNA sensing by cells with regulatory functions was essential for therapeutic responses to manifest. Intact STING and IFNαβ receptor genes, but not IFNγ receptor genes, were essential for therapeutic responses to DNPs to manifest. Treatments with cyclic diguanylate monophosphate (c-diGMP) to activate STING also delayed EAE onset and reduced disease severity. Therapeutic responses to DNPs were critically dependent on indoleamine 2,3 dioxygenase (IDO) enzyme activity in hematopoietic cells. Thus DNPs and c-diGMP attenuate EAE by inducing dominant T cell regulatory responses via the STING-IFNαβ-IDO pathway that suppress CNS-specific autoimmunity. These findings reveal dichotomous roles for the STING-IFNαβ pathway in either stimulating or suppressing autoimmunity and identify STING activating reagents as a novel class of immune modulatory drugs. PMID:24799564

  16. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP)

    PubMed Central

    Murphy, Stephen F.; Schaeffer, Anthony J.; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

    2015-01-01

    Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90–95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17’s role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS. PMID:25933188

  17. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

    PubMed

    Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

    2015-01-01

    Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  18. Pemphigus vulgaris in a patient with arthritis and uveitis: successful treatment with immunosuppressive therapy and acyclovir.

    PubMed

    Pranteda, G; Carlesimo, M; Bottoni, U; Di Napoli, A; Muscianese, M; Pimpinelli, F; Cordiali, P; Laganà, B; Pranteda, G; Di Carlo, A

    2014-01-01

    A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated. © 2014 Wiley Periodicals, Inc.

  19. Corticosteroid implants for chronic non-infectious uveitis

    PubMed Central

    Brady, Christopher J; Villanti, Andrea C; Law, Hua Andrew; Rahimy, Ehsan; Reddy, Rahul; Sieving, Pamela C; Garg, Sunir J; Tang, Johnny

    2016-01-01

    Background Uveitis is a term used to describe a heterogeneous group of intraocular inflammatory diseases of the anterior, intermediate, and posterior uveal tract (iris, ciliary body, choroid). Uveitis is the fifth most common cause of vision loss in high-income countries, accounting for 5% to 20% of legal blindness, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of acute treatment for all anatomical subtypes of non-infectious uveitis and can be administered orally, topically with drops or ointments, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation. Objectives To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlledtrials.com) (last searched 15 April 2013), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform(ICTRP) (www.who.int/ictrp/search/en).We did not use any date or language restrictions in the electronic search for studies. We last searched the electronic databases on 6 November 2015. We also searched reference lists of included study reports, citation databases, and abstracts and clinical study presentations from professional meetings. Selection criteria We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone intravitreal implants with standard

  20. Uveitis in juvenile idiopathic arthritis.

    PubMed

    Heiligenhaus, Arnd; Minden, Kirsten; Föll, Dirk; Pleyer, Uwe

    2015-02-06

    Juvenile idiopathic arthritis (JIA) is the most common systemic disease causing uveitis in childhood, with a prevalence of 10 per 100 000 persons. JIA often takes a severe inflammatory course, and its complications often endanger vision. This review is based on pertinent articles retrieved by a selective literature search up to 18 August 2014 and on the current interdisciplinary S2k guideline on the diagnostic evaluation and anti-inflammatory treatment of juvenile idiopathic uveitis. Uveitis arises in roughly 1 in 10 patients with JIA. Regular eye check-ups should be performed starting as soon as JIA is diagnosed. 75-80% of patients are girls; antinuclear antibodies are found in 70-90%. The risk to vision is higher if JIA begins in the preschool years. As for treatment, only a single, small-scale randomized controlled trial (RCT) and a small number of prospective trials have been published to date. Topical corticosteroids should be given as the initial treatment. Systemic immunosuppression is needed if irritation persists despite topical corticosteroids, if new complications arise, or if the topical steroids have to be given in excessively high doses or have unacceptable side effects. If the therapeutic effect remains inadequate, conventional and biological immune modulators can be given as add-on (escalation) therapy. Treatment lowers the risk of uveitis and its complications and thereby improves the prognosis for good visual function. Severely affected patients should be treated in competence centers to optimize their long-term outcome. Multidisciplinary, individualized treatment is needed because of the chronic course of active inflammation and the ensuing high risk of complications that can endanger vision. Future improvements in therapy will be aided by prospective, population-based registries and by basic research on biomarkers for the prediction of disease onset, prognosis, tissue damage, and therapeutic response.

  1. Overview and recent developments in the medical management of paediatric uveitis.

    PubMed

    Pilly, Bertrand; Heath, Greg; Tschuor, Patrizia; Lightman, Susan; Gale, Richard P

    2013-09-01

    Although rarer than its adult counterpart, non-infectious uveitis remains a significant cause of ocular morbidity in children. Owing to the chronicity of the disorder and when refractory to first-line treatment, namely corticosteroids, systemic immunosuppressive treatment may be required to control the disease. Following a literature search using the keywords 'paediatric uveitis', 'juvenile idiopathic arthritis-associated uveitis', 'immunosuppression' and 'treatment', we reviewed the range and effectiveness of treatments employed in the management of non-infectious, paediatric uveitis. Corticosteroids (topical, periocular, intraocular or systemic) remain the initial drug of choice in ameliorating the signs and symptoms of non-infectious paediatric uveitis. Failure to control the disease and/or failure to reduce the oral dose of prednisolone at least 0.15 mg/kg within 4 weeks often requires additional immunosuppressant therapy. Methotrexate and azathioprine have shown to be effective in the management of juvenile idiopathic arthritis (JIA)-associated uveitis with the former considered the first-line corticosteroid-sparing agent. Biologic therapies are increasingly used earlier in the disease with investigators in the UK currently recruiting patients for the SYCAMORE trial evaluating the efficacy of methotrexate and adalimumab vs methotrexate alone for the treatment for JIA-associated uveitis. Until further randomised controlled trials are conducted, the use of other biologic agents should only be used with an appreciation that there are potentially unknown side-effects and that there is not a full knowledge of their efficacy.

  2. High salt intake does not exacerbate murine autoimmune thyroiditis

    PubMed Central

    Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

    2014-01-01

    Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

  3. Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pestronk, A.; Drachman, D.B.; Teoh, R.

    1983-08-01

    A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used tomore » repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.« less

  4. Antigen-specific Immunotherapeutic Vaccine for Experimental Autoimmune Myasthenia Gravis

    PubMed Central

    Luo, Jie; Lindstrom, Jon

    2014-01-01

    Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are caused by antibody-mediated autoimmune responses to muscle nicotinic acetylcholine receptors (AChRs) that impair neuromuscular transmission thereby causing muscle weakness. Previously, we discovered that i. p. injection of a therapeutic vaccine consisting of bacterially-expressed cytoplasmic domains of human AChR subunits reduced development of chronic EAMG in rats. Here we show that immunization with the therapeutic vaccine in adjuvant does not induce EAMG, thus is safe. Potency and efficacy of the therapeutic vaccine were greatly increased by administering repeated low doses subcutaneously in incomplete Freund’s adjuvant. Onset of chronic EAMG could be prevented. Established chronic EAMG could be rapidly reversed, modeling therapy of chronic MG. Therapy reduced pathological antibodies assayed by immune precipitation of a main immunogenic region chimera. Successfully treated rats exhibited long-term resistance to re-induction of EAMG, modeling a lasting cure of MG. A long-term effect of therapy was to change isotype of the pathogenic antibody response from IgG2b that fixes complement to IgG1 that does not. Prevention and reversal of chronic EAMG was not caused by the isotype switch, but the isotype switch may contribute to resistance to reinduction of EAMG. Immunization with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. PMID:25288571

  5. Patterns of uveitis in a tertiary eye care center in Iran.

    PubMed

    Soheilian, Masood; Heidari, Kumars; Yazdani, Shahin; Shahsavari, Mohsen; Ahmadieh, Hamid; Dehghan, Mohammad

    2004-12-01

    To identify the distribution and characteristics of new uveitis referrals to a tertiary eye care center in Tehran. A three-year prospective study was carried out to obtain information on 544 new patients referred with uveitis. A complete ophthalmologic examination was performed in all cases; a routine set of tests and an additional battery of directed workup were conducted when indicated. Mean age was 32.3 years. There was no significant sex predominance. The most common forms of uveitis were anterior (38.4%) vs. other anatomical forms, chronic (62.1%) vs. acute (28.3%), nongranulomatous (85.5%) vs. granulomatous (14.5%), and noninfectious (83.5%) vs. infectious (16.5%). With regard to etiology, 45.5% were idiopathic, 19.9% were due to specific ocular disease, and 37.3% were associated with systemic disorders. Behcet's disease was the most common noninfectious disease and toxoplasmosis the most common infectious entity. The most prevalent causes were idiopathic, Fuchs' heterochromic iridocylitis, and seronegative spondyloarthropathies in anterior uveitis; toxoplasmosis, Eales disease, and toxocariasis in posterior uveitis; idiopathic, sarcoidosis, and multiple sclerosis in intermediate uveitis; and, finally, Behcet's disease, idiopathic, and Vogt-Koyanagi-Harada syndrome in panuveitis. The most frequent cause in patients under 16 years of age was pars planitis. Over 80% of the patients belonged to middle-to-upper socioeconomic classes. Uveitis significantly affected patients' lives in 63.1% of the cases. Although the current study was performed at a referral center, it may reflect to some extent the different distribution of uveitis in Iran and probably other Middle Eastern countries. Some entities such as presumed ocular histoplasmosis were not found, cytomegalovirus retinitis and birdshot chorioretinopathy were extremely rare, and HLA-B27-associated iridocyclitis was less commonly observed. In contrast, Behcet's disease, Fuchs' heterochromic iridocyclitis, Eales

  6. Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging.

    PubMed

    Denniston, Alastair K; Keane, Pearse A; Srivastava, Sunil K

    2017-05-01

    Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

  7. The Future Is Now: Biologics for Non-Infectious Pediatric Anterior Uveitis.

    PubMed

    Lerman, Melissa A; Rabinovich, C Egla

    2015-08-01

    Anterior uveitis (AU), inflammation of the iris, choroid or ciliary body, can cause significant eye morbidity, including visual loss. In the pediatric age group, the most common underlying diagnosis for AU is juvenile idiopathic associated uveitis and idiopathic AU, which are the focus of this paper. AU is often resistant to medications such as topical corticosteroids and methotrexate. In the past 15 years, biologic agents (biologics) have transformed treatment. In this review, we discuss those in widespread use and those with more theoretical applications for anterior uveitis. Tumor necrosis factor alpha inhibitors (anti-TNFα) have been available the longest and are used widely to treat pediatric uveitis. The effects of anti-TNFα in children are described mostly in small retrospective case series. Together, the literature suggests that the majority of children treated with anti-TNFα achieve decreased uveitis activity and reduced corticosteroid burden. However, many will have disease flares even on treatment. Only a few small studies directly compare outcomes between alternate anti-TNFα (infliximab and adalimumab). The use of different uveitis grading systems, inclusion criteria, and outcome measures makes cross-study comparisons difficult. Whether the achievement and maintenance of inactive disease occurs more frequently with certain anti-TNFα remains controversial. Newer biologics that modulate the immune system differently (e.g., interfere with Th17 activation through IL-17a and IL-6 blockade, limit T lymphocyte costimulation, and deplete B lymphocytes), have shown promise for uveitis. Studies of these agents are small and include mostly adults. Additional biologics are also being explored to treat uveitis. With their advent, we are hopeful that outcomes will ultimately be improved for children with AU. With many biologics available, much work remains to identify the optimal inflammatory pathway to target in AU.

  8. Impaired autophagy in macrophages promotes inflammatory eye disease.

    PubMed

    Santeford, Andrea; Wiley, Luke A; Park, Sunmin; Bamba, Sonya; Nakamura, Rei; Gdoura, Abdelaziz; Ferguson, Thomas A; Rao, P Kumar; Guan, Jun-Lin; Saitoh, Tatsuya; Akira, Shizuo; Xavier, Ramnik; Virgin, Herbert W; Apte, Rajendra S

    2016-10-02

    Autophagy is critical for maintaining cellular homeostasis. Organs such as the eye and brain are immunologically privileged. Here, we demonstrate that autophagy is essential for maintaining ocular immune privilege. Deletion of multiple autophagy genes in macrophages leads to an inflammation-mediated eye disease called uveitis that can cause blindness. Loss of autophagy activates inflammasome-mediated IL1B secretion that increases disease severity. Inhibition of caspase activity by gene deletion or pharmacological means completely reverses the disease phenotype. Of interest, experimental uveitis was also increased in a model of Crohn disease, a systemic autoimmune disease in which patients often develop uveitis, offering a potential mechanistic link between macrophage autophagy and systemic disease. These findings directly implicate the homeostatic process of autophagy in blinding eye disease and identify novel pathways for therapeutic intervention in uveitis.

  9. CNS Plasmacytoid Dendritic Cells Regulate the Severity of Relapsing Experimental Autoimmune Encephalomyelitis1

    PubMed Central

    Bailey-Bucktrout, Samantha L.; Caulkins, Sarah C.; Goings, Gwendolyn; Fischer, Jens A. A.; Dzionek, Andrzej; Miller, Stephen D.

    2010-01-01

    Plasmacytoid dendritic cells (pDC) have both stimulatory and regulatory effects on T cells. pDCs are a major CNS-infiltrating DC population during experimental autoimmune encephalomyelitis (EAE), but unlike myeloid DCs (mDC) have a minor role in T cell activation and epitope spreading. We show that depletion of pDCs during either the acute or relapse phases of EAE resulted in exacerbation of disease severity. pDC depletion significantly enhanced CNS but not peripheral CD4+ T cell activation, as well as IL-17 and IFN-γ production. Moreover, CNS pDCs suppressed CNS mDC-driven production of IL-17, IFN-γ and IL-10 in an IDO-independent manner. The data demonstrate that pDCs play a critical regulatory role in negatively regulating pathogenic CNS CD4+ T cell responses highlighting a new role for pDCs in inflammatory autoimmune disease. PMID:18453561

  10. Clinical Manifestations and Outcome of Syphilitic Uveitis.

    PubMed

    Bollemeijer, Jan G; Wieringa, Wietse G; Missotten, Tom O A R; Meenken, Ina; ten Dam-van Loon, Ninette H; Rothova, Aniki; Los, Leonoor I

    2016-02-01

    To analyze visual outcome, effectiveness of various modes of antibiotic treatment, and prognostic factors in patients with serologically proven syphilitic uveitis. The clinical records of 85 patients (139 eyes) diagnosed with syphilitic uveitis between 1984 and 2013 at tertiary centers in The Netherlands were retrospectively analyzed. Mean age was 47 years (range, 27-73 years), 82.4% were male. HIV positivity was found in 28 (35.9%) patients; 13 were newly diagnosed. Most patients had pan (45.9%) or posterior (31.8%) uveitis. On average, logMAR visual acuity (VA) improved significantly from 0.55 at the start of syphilis treatment to 0.34 at 1 month and to 0.27 at 6 months follow-up. Most patients (86.7%) reached disease remission. No differences in efficacy between the various treatment regimens were found. A high logMAR VA at the start of syphilis treatment and a treatment delay of more than 12 weeks were prognostic for a high logMAR VA at 6 months follow-up. Chronicity was not related to any form of treatment, HIV status, or Venereal Disease Research Laboratory test outcome. In this large cohort of 85 patients with syphilitic uveitis, visual outcomes were favorable in the majority of cases. Visual outcome was dependent on VA at the start of syphilis treatment and treatment delay.

  11. Interobserver Agreement Among Uveitis Experts on Uveitic Diagnoses: The Standardization of Uveitis Nomenclature Experience.

    PubMed

    Jabs, Douglas A; Dick, Andrew; Doucette, John T; Gupta, Amod; Lightman, Susan; McCluskey, Peter; Okada, Annabelle A; Palestine, Alan G; Rosenbaum, James T; Saleem, Sophia M; Thorne, Jennifer; Trusko, Brett

    2018-02-01

    To evaluate the interobserver agreement among uveitis experts on the diagnosis of the specific uveitic disease. Interobserver agreement analysis. Five committees, each comprised of 9 individuals and working in parallel, reviewed cases from a preliminary database of 25 uveitic diseases, collected by disease, and voted independently online whether the case was the disease in question or not. The agreement statistic, κ, was calculated for the 36 pairwise comparisons for each disease, and a mean κ was calculated for each disease. After the independent online voting, committee consensus conference calls, using nominal group techniques, reviewed all cases not achieving supermajority agreement (>75%) on the diagnosis in the online voting to attempt to arrive at a supermajority agreement. A total of 5766 cases for the 25 diseases were evaluated. The overall mean κ for the entire project was 0.39, with disease-specific variation ranging from 0.23 to 0.79. After the formalized consensus conference calls to address cases that did not achieve supermajority agreement in the online voting, supermajority agreement overall was reached on approximately 99% of cases, with disease-specific variation ranging from 96% to 100%. Agreement among uveitis experts on diagnosis is moderate at best but can be improved by discussion among them. These data suggest the need for validated and widely used classification criteria in the field of uveitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. [Equine recurrent uveitis].

    PubMed

    Spiess, B M

    1997-01-01

    Equine recurrent uveitis is an important ocular disease and the most common cause for blindness in horses and mules worldwide. The anatomy, physiology, immunology and inflammatory reactions of the uveal tract are discussed. Possible etiologies and the clinical signs are described. A detailed description of possible therapies is given and the prognosis is discussed.

  13. Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis.

    PubMed

    Kalinina Ayuso, Viera; van de Winkel, Evelyne Leonce; Rothova, Aniki; de Boer, Joke Helena

    2011-02-01

    To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective case series. Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a

  14. Efficacy of golimumab on recurrent uveitis in HLA-B27-positive ankylosing spondylitis.

    PubMed

    Yazgan, Serpil; Celik, Ugur; Işık, Metin; Yeşil, Nesibe Karahan; Baki, Ali Erdem; Şahin, Hatice; Gencer, Ercan; Doğan, İsmail

    2017-02-01

    To evaluate the efficacy of golimumab on severe and frequent recurrent anterior uveitis in patients with HLA-B27-positive ankylosing spondylitis. In this study, 15 eyes of 12 HLA-B27-positive AS patients with resistant anterior uveitis who received 50 mg of subcutaneous golimumab (Gol) per month due to frequent uveitis recurrences were analyzed retrospectively between May 2013 and October 2015. Assessment criteria were uveitis activity, the number of recurrence of uveitis, visual acuity, systemic corticosteroid, or other drug requirement for maintenance of remission of AU. Twelve patients (15 eyes) with HLA-B27-positive ankylosing spondylitis and anterior uveitis have been treated with golimumab 50 mg/month. Remission of uveitis was observed in 12 eyes out of 15. Malign hypertension developed in one subject after the second dose of golimumab therefore the treatment was stopped and this subject was excluded from the study. Median follow-up time was 11 months (interquartile range: 8-18). No uveitic reaction was seen except in the patient who stopped treatment. No topical or systemic steroid necessity was needed except in two cases with oral 4 mg systemic maintenance. Visual acuity was significantly increased (p = 0.002). Golimumab may be a new and effective choice for maintaining remission and the prevention of recurrences of severe, resistant anterior uveitis in patients with HLA-B27-positive ankylosing spondylitis.

  15. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis.

    PubMed

    Foeldvari, Ivan; Wierk, Angela

    2005-02-01

    To assess the effectiveness of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) associated uveitis, which is still one of the most common causes of visual impairment. A retrospective chart review of patients with the diagnosis of uveitis associated with JIA between July 1, 2002, and December 31, 2002. Four hundred sixty-seven patients with JIA were followed. Thirty-eight had uveitis: 31 associated with oligoarticular JIA and 7 with psoriatic JIA. Twenty-five of the 38 patients received MTX; in 23 patients uveitis was the indication for MTX therapy. In the MTX treated group 46/50 eyes had uveitis, the mean (range) age at onset of uveitis was 7.82 years (1.8-15.8), and the mean age at onset of arthritis was 7.25 years (1.25-15.7). MTX treatment was started an average of 11.4 months (0-72) after the onset of uveitis. The mean MTX dose was 15.6 mg/m2. Remission occurred after 4.25 months (1-12). Mean duration of remission was 10.3 months (3-27). The total duration of MTX therapy was 661 months and patients were in remission for 417/661 months. In 6 patients MTX was discontinued after 12 months of remission. Four patients were still in remission after 7.5 months (1-14). MTX seems to be an effective therapy for JIA associated uveitis.

  16. The neuropeptide cortistatin attenuates experimental autoimmune myocarditis via inhibition of cardiomyogenic T cell‐driven inflammatory responses

    PubMed Central

    Delgado‐Maroto, Virginia; Falo, Clara P; Forte‐Lago, Irene; Adan, Norma; Morell, Maria; Maganto‐Garcia, Elena; Robledo, Gema; O'Valle, Francisco; Lichtman, Andrew H; Gonzalez‐Rey, Elena

    2017-01-01

    Background and purpose Myocarditis is an inflammatory and autoimmune cardiovascular disease that causes dilated myocardiopathy and is responsible for high morbidity and mortality worldwide. Cortistatin is a neuropeptide produced by neurons and cells of the immune and vascular systems. Besides its action in locomotor activity and sleep, cortistatin inhibits inflammation in different experimental models of autoimmune diseases. However, its role in inflammatory cardiovascular disorders is unexplored. Here, we investigated the therapeutic effects of cortistatin in a well‐established preclinical model of experimental autoimmune myocarditis (EAM). Experimental Approach We induced EAM by immunization with a fragment of cardiac myosin in susceptible Balb/c mice. Cortistatin was administered i.p. starting 7, 11 or 15 days after EAM induction. At day 21, we evaluated heart hypertrophy, myocardial injury, cardiac inflammatory infiltration and levels of serum and cardiac inflammatory cytokines, cortistatin and autoantibodies. We determined proliferation and cytokine production by heart draining lymph node cells in response to cardiac myosin restimulation. Key Results Systemic injection of cortistatin during the effector phase of the disease significantly reduced its prevalence and signs of heart hypertrophy and injury (decreased the levels of brain natriuretic peptide) and impaired myocardial inflammatory cell infiltration. This effect was accompanied by a reduction in self‐antigen‐specific T‐cell responses in lymph nodes and in the levels of cardiomyogenic antibodies and inflammatory cytokines in serum and myocardium. Finally, we found a positive correlation between cardiac and systemic cortistatin levels and EAM severity. Conclusions and Implications Cortistatin emerges as a new candidate to treat inflammatory dilated cardiomyopathy. PMID:27922195

  17. Eosinophils in Autoimmune Diseases

    PubMed Central

    Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

    2017-01-01

    Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

  18. Suppression of chronic experimental autoimmune neuritis by nasally administered recombinant rat interleukin-6

    PubMed Central

    DERETZI, G; PELIDOU, S-H; ZOU, L-P; QUIDING, C; MIX, E; LEVI, M; WAHREN, B; ZHU, J

    1999-01-01

    Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as experimental model for human immune-demyelinating neurophathies, especially the Guillain–Barré syndrome. In this study, we examined the effect of recombinant rat interleukin-6 (rrIL-6) on chronic EAN in Lewis rats induced by immunization with P2 peptide 57-81 and Freund’s complete adjuvant (FCA). Nasal administration of rat rIL-6 (1 μg/rat/day) beginning in the initial phase of EAN as a therapeutic agent, decreased the severity and the duration of clinical EAN. Low-grade inflammation and suppression of regional demyelination within the sciatic nerves were seen in rrIL-6-treated rats. Hyporesponsiveness of lymph node T cells, down-regulation of serum tumour necrosis factor-α (TNF-α) and increased levels of P2-specific immunoglobulin G1 (IgG1) antibodies document that nasal administration of rrIL-6 was effective systemically. However, because of the non-specific nature of the treatment and multiple effects of IL-6, more experience and great caution are needed, before nasal administration of IL-6 can be considered as a treatment of human autoimmune demyelinating neurophathies. PMID:10447716

  19. Ultra-Widefield Fluorescein Angiography in Intermediate Uveitis.

    PubMed

    Laovirojjanakul, Wipada; Acharya, Nisha; Gonzales, John A

    2017-10-17

    To examine associations between pattern of vascular leakage on ultrawide-field fluorescein angiography (UWFFA) and visual acuity, cystoid macular edema (CME), and inflammatory activity in intermediate uveitis. Single center cross-sectional, retrospective review of medical records, spectral domain optical coherence tomography (SD-OCT) and angiographic images of intermediate uveitis patients who underwent UWFFA over a 12-month period. Forty-one eyes from 24 patients were included. Twelve eyes (29%) exhibited peripheral leakage, 26 eyes (64%) had diffuse leakage and three eyes (7%) had no leakage. Diffuse leakage was associated with 0.2 logMAR worse visual acuity than peripheral leakage (p = 0.02). There was no statistically significant difference in the odds of having CME when diffuse leakage was compared to peripheral leakage. UWFFA identifies retinal vascular pathology in intermediate uveitis not present on clinical examination. Diffuse retinal vascular leakage was associated with worse visual acuity when compared to peripheral and no leakage patterns.

  20. Abatacept in the treatment of severe, longstanding, and refractory uveitis associated with juvenile idiopathic arthritis.

    PubMed

    Tappeiner, Christoph; Miserocchi, Elisabetta; Bodaghi, Bahram; Kotaniemi, Kaisu; Mackensen, Friederike; Gerloni, Valeria; Quartier, Pierre; Lutz, Thomas; Heiligenhaus, Arnd

    2015-04-01

    Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA). Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor-α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications. In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup. A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

  1. Autoimmune synaptopathies.

    PubMed

    Crisp, Sarah J; Kullmann, Dimitri M; Vincent, Angela

    2016-02-01

    Autoantibodies targeting proteins at the neuromuscular junction are known to cause several distinct myasthenic syndromes. Recently, autoantibodies targeting neurotransmitter receptors and associated proteins have also emerged as a cause of severe, but potentially treatable, diseases of the CNS. Here, we review the clinical evidence as well as in vitro and in vivo experimental evidence that autoantibodies account for myasthenic syndromes and autoimmune disorders of the CNS by disrupting the functional or structural integrity of synapses. Studying neurological and psychiatric diseases of autoimmune origin may provide new insights into the cellular and circuit mechanisms underlying a broad range of CNS disorders.

  2. Epidemiology of uveitis in a Western urban multiethnic population. The challenge of globalization.

    PubMed

    Llorenç, Victor; Mesquida, Marina; Sainz de la Maza, Maite; Keller, Johannes; Molins, Blanca; Espinosa, Gerard; Hernandez, María V; Gonzalez-Martín, Julian; Adán, Alfredo

    2015-09-01

    To report the anatomical pattern and etiological spectrum of uveitis in an urban multi-ethnic population from Barcelona, Spain. General and specific epidemiological data for the most prevalent aetiologies are also calculated. A cross-sectional study of consecutive uveitis cases was performed between 1 January 2009 and 31 December 2012. Exogenous endophthalmitis, surgery-related, post-traumatic and toxic uveitis along with masquerade syndromes were excluded. Anatomical (Standard Uveitis Nomenclature criteria) and aetiological patterns (by tailored tests), age, sex, geographical origin and laterality were analysed. Mean incidence and prevalence were calculated for a mid-period reference population. From 1022 patients included, 52% were anterior uveitis (AU), 23% posterior, 15% panuveitis and 9% intermediate uveitis. Aetiologically, 26% were unclassifiable, 29% infectious, 25% associated with systemic immune diseases, and 20% corresponded to ocular-specific syndromes. Among classified causes, herpesvirus (12%), toxoplasma (7%), Behçet's disease (BD) (5%), HLA-B27-isolated AU (5%), ankylosing spondylitis (5%), tuberculosis-related uveitis (TRU) (5%), birdshot chorioretinopathy (3%) and sarcoidosis (3%) were the most frequent. Non-Spanish origin was recorded in 22%, with 47% of Vogt-Koyanagi-Harada and 36% of toxoplasma cases coming from South America, 10% of BD and 11% of TRU from Africa and 24% of TRU cases from Asia. A mean annual incidence of 51.91 cases/100,000 inhabitants was found for the referral population. In our referral area, 74% of the uveitis cases can be correctly classified. A large myriad of uveitis aetiologies with a strong geographical origin burden are found in Western urban multi-ethnic populations. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  3. Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood.

    PubMed

    Doycheva, Deshka; Zierhut, Manfred; Blumenstock, Gunnar; Sobolewska, Bianka; Voykov, Bogomil; Hohmann, Johanna; Spitzer, Martin S; Deuter, Christoph

    2016-08-01

    To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis. Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects. From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed. Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Detection of Leptospira spp. in the aqueous humor of horses with naturally acquired recurrent uveitis.

    PubMed

    Faber, N A; Crawford, M; LeFebvre, R B; Buyukmihci, N C; Madigan, J E; Willits, N H

    2000-07-01

    Leptospiral organisms have long been presumed to be associated with the presence of equine recurrent uveitis. This project was undertaken to determine the presence of Leptospira spp. in the aqueous humor of horses with uveitis to determine if there was an association with inflammation. Thirty horses were determined to have recurrent uveitis based on clinical evaluation or history. Sixteen horses were judged clinically and historically to be free of uveitis and were used as controls. Aqueous humor samples were cultured and evaluated by PCR for the presence of Leptospira DNA. Serum was collected and evaluated for the presence of antibodies against five serovars in a leptospirosis panel. Twenty-one of 30 horses with recurrent uveitis and one of 16 uveitis-free horses were positive by PCR for the presence of Leptospira DNA. Six of these 21 horses with uveitis were culture positive for leptospires from the aqueous humor. Serologic results did not correlate well with the presence of Leptospira DNA or organisms in the aqueous humor. Leptospira spp. are present in a high percentage of horses with naturally occurring recurrent uveitis.

  5. Detection of Leptospira spp. in the Aqueous Humor of Horses with Naturally Acquired Recurrent Uveitis

    PubMed Central

    Faber, Nick A.; Crawford, Melissa; LeFebvre, Rance B.; Buyukmihci, Nedim C.; Madigan, John E.; Willits, Neil H.

    2000-01-01

    Leptospiral organisms have long been presumed to be associated with the presence of equine recurrent uveitis. This project was undertaken to determine the presence of Leptospira spp. in the aqueous humor of horses with uveitis to determine if there was an association with inflammation. Thirty horses were determined to have recurrent uveitis based on clinical evaluation or history. Sixteen horses were judged clinically and historically to be free of uveitis and were used as controls. Aqueous humor samples were cultured and evaluated by PCR for the presence of Leptospira DNA. Serum was collected and evaluated for the presence of antibodies against five serovars in a leptospirosis panel. Twenty-one of 30 horses with recurrent uveitis and one of 16 uveitis-free horses were positive by PCR for the presence of Leptospira DNA. Six of these 21 horses with uveitis were culture positive for leptospires from the aqueous humor. Serologic results did not correlate well with the presence of Leptospira DNA or organisms in the aqueous humor. Leptospira spp. are present in a high percentage of horses with naturally occurring recurrent uveitis. PMID:10878072

  6. Diagnosis and treatment of tuberculous uveitis in a low endemic setting.

    PubMed

    Vos, A G; Wassenberg, M W M; de Hoog, J; Oosterheert, J J

    2013-11-01

    To determine factors associated with the diagnosis of tuberculous uveitis and the response to anti-tuberculous treatment (ATT). A retrospective case study was performed at the University Medical Centre Utrecht between October 2007 and December 2009. Patients with possible tuberculous uveitis (TBU) were selected from all patients with an unexplained uveitis. Demographics, ethnicity, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tuberculin skin test (TST), QuantiFERON (QFT) test, and ocular findings were evaluated. An interdisciplinary panel discussed if there was a presumed TBU and decided to start treatment. When there was a decrease in intraocular cell count and/or improvement in visual acuity after ATT, the confirmation of presumed TBU was made. Of 585 patients with unexplained uveitis, 66 (11.3%) fulfilled the definition of possible TBU. Ten (15.4%) patients were regarded as having presumed TBU and received ATT. All of them had latent tuberculosis (LTB). The ocular situation improved in seven patients (70%). A history of TB contact, abnormalities on chest radiology, and extraocular manifestations of TB were associated with a good response to ATT in the case of presumed tuberculous uveitis. Tuberculous uveitis remains difficult to diagnose. No clearly correlating factors that predicted the response to ATT, including ocular parameters, could be identified. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Strain-related effects of fenbendazole treatment on murine experimental autoimmune encephalomyelitis.

    PubMed

    Ramp, A A; Hall, C; Orian, J M

    2010-07-01

    Parasitic infections are a concern in animal facilities, in view of their influence on physiological processes and the immune status of animals. Pinworms are effectively controlled with the anthelminthic fenbendazole (FBZ, [5-(phenylthio)-1H-benzamidazol-2-yl]carbamic acid methyl ester; C(15)H(13)N(3)O(2)S); however, questions remain as to whether prolonged FBZ exposure alters the disease course in specific experimental models, such as those pertaining to the immune system. We report that a three-month regimen of FBZ-medicated feed severely affected the onset and disease severity of murine experimental autoimmune encephalomyelitis (EAE), a disease that mimics multiple sclerosis. Differences were recorded between mouse strains used. Our data suggest that where the use of FBZ is mandatory, its full effect should be verified on the particular EAE variant adopted by the laboratory.

  8. Tocilizumab treatment for refractory uveitis-related cystoid macular edema.

    PubMed

    Adán, Alfredo; Mesquida, Marina; Llorenç, Victor; Espinosa, Gerard; Molins, Blanca; Hernández, Maria V; Pelegrín, Laura

    2013-11-01

    This retrospective study investigated the efficacy of tocilizumab (TCZ), a fully humanized antibody that binds both to soluble and membrane bound IL-6 receptors, for the treatment of uveitis-related cystoid macular edema (CME) refractory to immunomodulatory therapy. Five refractory patients with uveitis-related CME who received TCZ between January and August 2012 were included. All patients received 8 mg/kg TCZ at 4-week intervals. Data regarding patient demographics, use of immunosuppressive drugs, biologic agents or intravitreal therapies prior to TCZ infusions were collected. Main outcome measure was central foveal thickness (CFT) measured by optical coherence tomography at 6 months. Secondary outcome measures were degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria) and visual acuity (logarithm of the minimum angle of resolution [log-MAR]) at month 6. Adverse events (AEs) related to TCZ therapy were also assessed. Eight eyes from five patients (all females) were included. Mean age was 49.4 years (range, 30-68). Mean follow-up was 8.4 months (range, 6-12). Before TCZ, all patients received and failed conventional immunosuppressive therapy and had received at least another biologic agent. Uveitis diagnoses were Birdshot chorioretinopathy (n = 3), juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), and idiopathic panuveitis (n = 1). Mean evolution of CME was 13.4 years (range, 2-30). Mean baseline CFT (95% confidence interval) was 602 ± 236 μm at baseline, 386 ± 113 μm at month 1 (p = 0.006), 323 ± 103 μm at month 3 (p = 0.026), and 294.5 ± 94.5 μm at month 6 (p = 0.014). Median best-corrected visual acuity (BCVA) improved from 0.66 ± 0.57 at baseline to 0.47 ± 0.62 at month 6 (p = 0.035). After 6 months, an improvement of ≥ 2 lines of BCVA was observed in 50% of eyes (p = 0.028) remained stable in 25% and worsened in none of the patients. Sustained uveitis remission was

  9. Syphilitic retinitis and uveitis in HIV-positive adults.

    PubMed

    Hughes, Edward H; Guzowski, Magdalena; Simunovic, Matthew P; Hunyor, Alex P; McCluskey, Peter

    2010-12-01

    The incidence of new infection with syphilis is increasing, particularly in men who have sex with men, with HIV co-infection common. There has been a corresponding increase in ophthalmic manifestations that can be varied in presentation. Thirteen consecutive patients with syphilitic uveitis presenting to two ophthalmic departments in Sydney are described. Twelve patients were male, of whom 10 were homosexual and six HIV-positive. Peripheral retinitis with panuveitis was the commonest ophthalmic presentation (n = 7, 54%), and six cases were initially treated with vitreous tap and intravitreal foscarnet as a precaution in case of viral retinitis. Retinitis was present in six of six (100%) HIV-positive and only one of seven (14%) HIV-negative patients (χ² 10.6, P < 0.01). Other ophthalmic presentations included anterior uveitis, vitritis, multifocal choroiditis, scleritis and papillitis. All patients responded to 10-14 days' intravenous penicillin with good final visual outcomes (6/12 or better in all eyes). This case series reinforces the importance of considering syphilis in the differential diagnosis of many ocular presentations, but in particular retinitis. Retinitis appears to be the predominant presentation in HIV-infected individuals, suggesting that HIV infection may somehow modulate the disease. © 2010 The Authors. Clinical and Experimental Ophthalmology © 2010 Royal Australian and New Zealand College of Ophthalmologists.

  10. Anti-inflammatory and ultrastructural effects of Turkish propolis in a rat model of endotoxin-induced uveitis.

    PubMed

    Ertürküner, Salime Pelin; Yaprak Saraç, Elif; Göçmez, Semil Selcen; Ekmekçi, Hakan; Öztürk, Zeynep Banu; Seçkin, İsmail; Sever, Özkan; Keskinbora, Kadircan

    2016-01-01

    Experimental animal models of acute uveitis, an inflammatory eye disease, can be established via endotoxin-induced inflammation. Propolis, a natural substance collected by honeybees from buds and tree exudates, has antioxidant, antibacterial, antiviral, and anti-inflammatory effects. We investigated the effects of propolis, obtained from the Sakarya province of Turkey, on endotoxin-induced uveitis using immunohistochemical, ultrastructural, and biochemical approaches. Male Wistar albino rats (n = 6/group) received intraperitoneal (ip) lipopolysaccharide (LPS) endotoxin (150 μg/kg) followed by aqueous extract of propolis (50 mg/kg ip) or vehicle; two additional groups received either saline (control) or propolis only. After 24 h, aqueous humor (AH) was collected from both eyes of each animal for analysis of tumor necrosis factor-α (TNF-α) and hypoxia-inducible factor-1α (HIF-1α). Right eyeballs were paraffin-embedded for immunohistochemical staining of nuclear factor κB (NF-κB)/p65 and left eyeballs were araldite-embedded for ultrastructural analysis. Treatment of LPS-induced uveitis with propolis significantly reduced ciliary body NF-κB/p65 immunoreactivity and AH levels of HIF-1α and TNF-α. Ultrastructural analysis showed fewer vacuoles and reduced mitochondrial degeneration in the retinal pigment epithelium, as compared to the uveitis group. The intercellular spaces of the inner nuclear layer and outer limiting membrane were comparable with those of the control group; no polymorphonuclear cells or stasis was observed in intravascular or extravascular spaces. This is the first report demonstrating an anti-inflammatory effect of Turkish propolis in a rat model of LPS-induced acute uveitis, suggesting a therapeutic potential of propolis for the treatment of inflammatory ophthalmic diseases.

  11. Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18.

    PubMed

    Im, S H; Barchan, D; Maiti, P K; Raveh, L; Souroujon, M C; Fuchs, S

    2001-10-01

    Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine that plays an important role in interferon gamma (IFN-gamma) production and IL-12-driven Th1 phenotype polarization. Increased expression of IL-18 has been observed in several autoimmune diseases. In this study we have analyzed the role of IL-18 in an antibody-mediated autoimmune disease and elucidated the mechanisms involved in disease suppression mediated by blockade of IL-18, using experimental autoimmune myasthenia gravis (EAMG) as a model. EAMG is a T cell-regulated, antibody-mediated autoimmune disease in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1- and Th2-type responses are both implicated in EAMG development. We show that treatment by anti-IL-18 during ongoing EAMG suppresses disease progression. The protective effect can be adoptively transferred to naive recipients and is mediated by increased levels of the immunosuppressive Th3-type cytokine TGF-beta and decreased AChR-specific Th1-type cellular responses. Suppression of EAMG is accompanied by down-regulation of the costimulatory factor CD40L and up-regulation of CTLA-4, a key negative immunomodulator. Our results suggest that IL-18 blockade may potentially be applied for immunointervention in myasthenia gravis.

  12. [Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy].

    PubMed

    Heiligenhaus, A; Tappeiner, C; Walscheid, K; Heinz, C

    2016-05-01

    Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

  13. Association between intermediate uveitis and toxocariasis in the Korean population

    PubMed Central

    Kwon, Jin-woo; Sim, Yoonseob; Jee, Donghyun

    2017-01-01

    Abstract The aim of the study was to investigate the characteristics of ocular toxocariasis (OT) presenting with intermediate uveitis in the Korean population. We studied intermediate uveitis patients using ocular and systemic evaluations and a Toxocara IgG serology test. Of 50 intermediate uveitis patients, 19 were seropositive for Toxocara IgG. Of the 19 OT patients, 4 presented with recurrence within 6 months and were significantly younger than nonrecurrence patients (P = 0.009). Thirteen patients had a history of eating raw cow liver. There were 14 males and 5 females in the OT group, and 11 males and 20 females in the non-OT group (P = 0.009). There was bilateral involvement in 7 out of 19 patients in the OT group, and 20 out of 31 patients in non-OT group (P = 0.033). Intermediate uveitis patients in OT were predominately male and had more unilateral presentation than non-OT patients. PMID:28151857

  14. Association between intermediate uveitis and toxocariasis in the Korean population.

    PubMed

    Kwon, Jin-Woo; Sim, Yoonseob; Jee, Donghyun

    2017-02-01

    The aim of the study was to investigate the characteristics of ocular toxocariasis (OT) presenting with intermediate uveitis in the Korean population.We studied intermediate uveitis patients using ocular and systemic evaluations and a Toxocara IgG serology test.Of 50 intermediate uveitis patients, 19 were seropositive for Toxocara IgG. Of the 19 OT patients, 4 presented with recurrence within 6 months and were significantly younger than nonrecurrence patients (P = 0.009). Thirteen patients had a history of eating raw cow liver.There were 14 males and 5 females in the OT group, and 11 males and 20 females in the non-OT group (P = 0.009). There was bilateral involvement in 7 out of 19 patients in the OT group, and 20 out of 31 patients in non-OT group (P = 0.033).Intermediate uveitis patients in OT were predominately male and had more unilateral presentation than non-OT patients.

  15. Chronic Non-infectious Uveitis in Patients with Juvenile Idiopathic Arthritis.

    PubMed

    Kolomeyer, Anton M; Tu, Yufei; Miserocchi, Elisabetta; Ranjan, Mangala; Davidow, Amy; Chu, David S

    2016-08-01

    To describe clinical findings and analyze treatment evolution of chronic, non-infectious uveitis in patients with juvenile idiopathic arthritis (JIA). A total of 82 patients (147 eyes) with JIA-related uveitis treated for ≥2 months were included (78% females; 79% bilateral uveitis; 74% anterior uveitis). Outcome measures were visual acuity (VA), inflammation control, side-effects, and surgical procedures. Mean ± SD age at diagnosis was 4.9 ± 3.8 years; mean ± SD follow-up time was 8.7 ± 7.8 years. Mean VA did not significantly change throughout the study. Three (2%) eyes resulted in no light perception (NLP) vision. Thirty (37%) patients underwent 69 procedures. In total, 41 (50%) patients achieved inflammation control. TNF-α inhibitors were significantly associated with inflammation control. Seven (8.5%) patients stopped treatment due to side-effects. JIA is a cause of significant ocular morbidity. TNF-α inhibitor use was associated with inflammation control. Prospective, randomized, double blind clinical trials in this regard are warranted.

  16. Levels of thrombopoietin in aqueous humor of patients with noninfectious acute anterior uveitis

    PubMed Central

    Mondejar, José-Juan; Salom, David; Garcia-Delpech, Salvador; Diaz-Llopis, Manuel

    2015-01-01

    Purpose To measure thrombopoietin (TPO) levels in the serum and aqueous humors of patients with noninfectious acute anterior uveitis. Methods A prospective, comparative, controlled study. Serum and aqueous humors were obtained from the eyes of 16 patients with noninfectious acute anterior uveitis. TPO levels were measured using an enzyme-linked immunosorbent assay (ELISA). The results obtained were compared with those of a control group. Results Serum concentrations of TPO were not significantly different between control individuals and patients with active anterior uveitis. Aqueous humor TPO levels were 54.46±16.24 pg/mL in the eyes of patients with uveitis, and 34.32±11.63 pg/mL in the eyes of controls. The difference between the two groups was significant (Mann–Whitney U-test for independent data, P=0.0008), with uveitis patients exhibiting significantly higher levels of TPO. Conclusion The high levels of TPO in the aqueous humors of uveitis patients points toward a cytoprotective role of this factor in inflammatory repair processes and the recovery of tissue homeostasis. PMID:26203218

  17. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

    PubMed

    Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

    2016-06-01

    To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  18. The Future is Now – Biologics for Non-Infectious Pediatric Anterior Uveitis

    PubMed Central

    Lerman, Melissa A.; Rabinovich, C. Egla

    2015-01-01

    Anterior uveitis (AU), inflammation of the iris, choroid, or ciliary body, can cause significant eye morbidity, including visual loss. In the pediatric age group, the most common underlying diagnosis for AU is juvenile idiopathic associated uveitis and idiopathic AU, which are the focus of this paper. AU is often resistant to medications such as topical corticosteroids and methotrexate. In the past 15 years, biologic agents (biologics) have transformed treatment. In this review, we discuss those in widespread use and those with more theoretical applications for anterior uveitis. Tumor Necrosis Factor alpha inhibitors (anti-TNFα) have been available the longest and are used widely to treat pediatric uveitis. The effects of anti-TNFα in children are described mostly in small retrospective case series. Together, the literature suggests that the majority of children treated with anti-TNFα achieve decreased uveitis activity and reduce corticosteroid burden. However, many will have disease flares even on treatment. Only a few small studies directly compare outcomes between alternate anti-TNFα (infliximab and adalimumab). The use of different uveitis grading systems, inclusion criteria, and outcome measures, makes cross-study comparisons difficult. Whether the achievement and maintenance of inactive disease occurs more frequently with certain anti-TNFα remains controversial. Newer biologics that modulate the immune system differently (e.g., interfere with TH17 activation through IL-17a and IL-6 blockade, limit T lymphocyte costimulation, and deplete B lymphocytes), have shown promise for uveitis. Studies of these agents are small and include mostly adults. Additional biologics are also being explored to treat uveitis. With their advent, we are hopeful that outcomes will ultimately be improved for children with AU. With many biologics available, much work remains to identify the optimal inflammatory pathway to target in AU. PMID:25893479

  19. Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis.

    PubMed

    Sepah, Yasir Jamal; Sadiq, Mohammad Ali; Chu, David S; Dacey, Mark; Gallemore, Ron; Dayani, Pouya; Hanout, Mostafa; Hassan, Muhammad; Afridi, Rubbia; Agarwal, Aniruddha; Halim, Muhammad Sohail; Do, Diana V; Nguyen, Quan Dong

    2017-11-01

    To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Randomized, controlled, multicenter clinical trial. STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6. A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was -83.88 ± 136.1 μm at month 6 (-131.5 ± 41.56 μm in Group 1 and -38.92 ± 13.7 μm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated. Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

    PubMed Central

    van den Hoogen, Ward J.; Laman, Jon D.; ’t Hart, Bert A.

    2017-01-01

    Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research. PMID:28928747

  1. Metals and kidney autoimmunity.

    PubMed Central

    Bigazzi, P E

    1999-01-01

    The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal

  2. Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Singh, Avneesh K.; Wilson, Michael T.; Hong, Seokmann; Olivares-Villagómez, Danyvid; Du, Caigan; Stanic, Aleksandar K.; Joyce, Sebastian; Sriram, Subramaniam; Koezuka, Yasuhiko; Van Kaer, Luc

    2001-01-01

    Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell–mediated autoimmunity. Vα14 natural killer T (NKT) cells are a subset of T lymphocytes that recognize glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I–like protein CD1d. Here, we show that activation of Vα14 NKT cells by the glycosphingolipid α-galactosylceramide (α-GalCer) protects susceptible mice against EAE. β-GalCer, which binds CD1d but is not recognized by NKT cells, failed to protect mice against EAE. Furthermore, α-GalCer was unable to protect CD1d knockout (KO) mice against EAE, indicating the requirement for an intact CD1d antigen presentation pathway. Protection of disease conferred by α-GalCer correlated with its ability to suppress myelin antigen-specific Th1 responses and/or to promote myelin antigen-specific Th2 cell responses. α-GalCer was unable to protect IL-4 KO and IL-10 KO mice against EAE, indicating a critical role for both of these cytokines. Because recognition of α-GalCer by NKT cells is phylogenetically conserved, our findings have identified NKT cells as novel target cells for treatment of inflammatory diseases of the central nervous system. PMID:11748281

  3. Increased spontaneous apoptosis of rat primary neurospheres in vitro after experimental autoimmune encephalomyelitis.

    PubMed

    Sajad, Mir; Zargan, Jamil; Sharma, Jyoti; Chawla, Raman; Arora, Rajesh; Umar, Sadiq; Khan, Haider A

    2011-06-01

    Survival of neuronal progenitors (NPCs) is a critical determinant of the regenerative capacity of brain following cellular loss. Herein, we report for the first time, the increased spontaneous apoptosis of the first acute phase of Experimental Autoimmune Encephalomyelitis (EAE) derived neurospheres in vitro. Neuronal as well as oligodendroglial loss occurs during experimental autoimmune encephalomyelitis (EAE). This loss is replenished spontaneously by the concomitant increase in the NPC proliferation evidenced by the presence of thin myelin sheaths in the remodeled lesions. However, remyelination depends upon the survival of NPCs and their lineage specific differentiation. We observed significant increase (P < 0.001) in number of BrdU (+) cells in ependymal subventricular zone (SVZ) in EAE rats. EAE derived NPCs showed remarkable increase in S-phase population which was indeed due to the decrease in G-phase progeny suggesting activation of neuronal progenitor cells (NPCs) from quiescence. However, EAE derived neurospheres showed limited survival in vitro which was mediated by the significantly (P < 0.01) depolarized mitochondria, elevated Caspase-3 (P < 0.001) and fragmentation of nuclear DNA evidenced by single cell gel electrophoresis. Our results suggest EAE induced spontaneous apoptosis of NPCs in vitro which may increase the possibility of early stage cell death in the negative regulation of the proliferative cell number and may explain the failure of regeneration in human multiple sclerosis.

  4. Visual Functioning and Health-related Quality-of-Life are Compromised in Patients with Uveitis.

    PubMed

    Hui, Michelle M; Wakefield, Denis; Patel, Ilesh; Cvejic, Erin; McCluskey, Peter J; Chang, John H

    2017-08-01

    To assess the vision-related (VR) and health-related (HR) quality-of-life (QoL) of patients with uveitis. In total, 60 patients with uveitis, 81 patients with diabetic retinopathy (DR), and 70 healthy subjects completed the National Eye Institute Visual Functioning Questionnaire and the Medical Outcome Study 36-Item Short Form. Patients with uveitis reported lower HR- and VR-QoL than healthy subjects (p<0.05) and lower VR-QoL (p<0.001) than patients with DR. For patients with uveitis, multiple linear regression analyses indicated that lower HR-QoL scores were predicted by younger age (p<0.01), while lower VR-QoL scores were predicted by poorer visual acuity (p<0.001), ocular comorbidities (p<0.05), and female sex (p<0.05). Patients with uveitis have significantly poorer VR- and HR-QoL than healthy control subjects. Uveitis has a more debilitating impact on VR-QoL than DR.

  5. Endothelial NOS-deficient mice reveal dual roles for nitric oxide during experimental autoimmune encephalomyelitis.

    PubMed

    Wu, Muzhou; Tsirka, Stella E

    2009-08-15

    Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by infiltration of T cells into the central nervous system (CNS) after compromise of the blood-brain barrier. A model used to mimic the disease in mice is experimental autoimmune encephalomyelitis (EAE). In this report, we examine the clinical and histopathological course of EAE in eNOS-deficient (eNOS-/-) mice to determine the role of nitric oxide (NO) derived from this enzyme in the disease progression. We find that eNOS-/- mice exhibit a delayed onset of EAE that correlates with delayed BBB breakdown, thus suggesting that NO production by eNOS underlies the T cell infiltration into the CNS. However, the eNOS-/- mice also eventually exhibit more severe EAE and delayed recovery, indicating that NO undertakes dual roles in MS/EAE, one proinflammatory that triggers disease onset, and the other neuroprotective that promotes recovery from disease exacerbation events.

  6. Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives

    PubMed Central

    Lang, Yue

    2018-01-01

    The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS. PMID:29805314

  7. Azathioprine in severe uveitis of Behçet's disease.

    PubMed

    Saadoun, D; Wechsler, B; Terrada, C; Hajage, D; Le Thi Huong, D; Resche-Rigon, M; Cassoux, N; Le Hoang, P; Amoura, Z; Bodaghi, B; Cacoub, P

    2010-12-01

    To investigate the efficacy and tolerance of azathioprine in severe uveitis related to Behçet's disease (BD). We reported 157 consecutive patients with severe uveitis (active posterior uveitis or panuveitis) fulfilling the international criteria for BD and treated with corticosteroids (0.5-1 mg/kg/day) and azathioprine (2.5 mg/kg/day). Long-term outcome and factors associated with complete remission were assessed. Mean±SD age at diagnosis was 29.9±10.1 years, with 71.3% men. At baseline, 59 patients (37.6%) had loss of useful vision, 54 (34.4%) had retinal vasculitis, 66 (42.0%) had panuveitis, and 132 (84.1%) had bilateral uveitis. Following azathioprine therapy, 81 patients (51.6%) were complete responders, 65 (41.4%) were partial responders, and 11 (7%) were nonresponders. The visual acuity significantly improved (P<0.001), and a significant decrease in the mean oral prednisone dosage (55.3 to 10.5 mg/day; P<0.001) was observed after therapy. Patients with retinal vasculitis (odds ratio [OR] 0.45 [95% confidence interval (95% CI) 0.2-0.9], P=0.02) and severe visual loss (OR 0.28 [95% CI 0.2-0.7], P<0.0001) at diagnosis were less likely to be complete responders. Azathioprine was well tolerated, with only 3 withdrawals due to hepatotoxic effects (n=2) and bacterial septicemia (n=1). Azathioprine represents an effective and safe therapy in patients with severe uveitis of BD. Copyright © 2010 by the American College of Rheumatology.

  8. Anterior chamber paracentesis to improve diagnosis and treatment of infectious uveitis in South Africa.

    PubMed

    Schaftenaar, Erik; Lecuona, Karin; Baarsma, Seerp; Meenken, Christina; Verjans, Georges; McIntyre, James; Peters, Remco

    2015-09-22

    Infectious uveitis is a significant cause of blindness in South Africa, especially among HIV-infected individuals. The visual outcome of uveitis depends on early clinical and laboratory diagnosis to guide therapeutic intervention. Analyses of aqueous humor, obtained by anterior chamber paracentesis, directs the differential diagnosis in infectious uveitis. However, although safe and potentially cost-effective, diagnostic anterior chamber paracentesis is not common practice in ophthalmic care across Africa. We seek to draw attention to this important procedure that could improve the diagnosis and prognosis of infectious uveitis.

  9. Controversies in juvenile idiopathic arthritis-associated uveitis.

    PubMed

    Zierhut, Manfred; Heiligenhaus, Arnd; deBoer, Joke; Cunningham, Emmett T; Tugal-Tutkun, Ilknur

    2013-06-01

    Abstract Juvenile idiopathic arthritis-associated uveitis (JIAU) accounts for a sizable proportion of uveitis cases in children and is an important cause of ocular morbidity in uveitis patients in this age group. The authors present the results of a survey conducted to obtain a better understanding of the current views and practices of ophthalmologists involved in the care of children with JIAU. A detailed questionnaire consisting of 54 questions addressing epidemiology, diagnosis, and therapy of JIAU was distributed to 67 uveitis specialists. The responses from 37 completed questionnaires were tabulated for this report. While the experts often agreed on aspects of the epidemiologic and clinical features of JIAU and its complications, considerable diversity of responses was noted-particularly with regard to practice patterns. Regarding diagnostics and disease monitoring, all experts favored ANA testing, whereas two-thirds also suggested HLA-B27 typing. Laser flare photometry was available to and routinely used by almost one-third of the experts. Optical coherence tomography (OCT) was used by more than half. The survey revealed an overall consensus on therapeutic strategies, including the use of both conventional immunosuppressive and biologic agents. Methotrexate was the initial choice for immunosuppression by most respondents. Most would add an anti-TNF-alpha agent following failure of traditional immunosuppressive therapy, and adalimumab was favored by almost half of the experts. Questions addressing the management of individual situations, such as the treatment of macular edema and perioperative management, revealed considerable differences in therapeutic approaches. The results of this survey support the development of international guidelines for the management of JIAU.

  10. Trends in patterns of anterior uveitis in a tertiary institution in singapore.

    PubMed

    Tan, Wai Jia; Poh, Eugenie W; Wong, Poh-Ying; Ho, Su-Ling; Lim, Wee-Kiak; Teoh, Stephen C

    2013-08-01

    To report the trends in etiology of patients with anterior uveitis (AU) in Singapore over 6 years. A retrospective review of the clinical records of all new patients who presented with anterior uveitis to the uveitis subspecialty clinic from 2005 to 2010 at Tan Tock Seng Hospital, Singapore. There were 552 new cases of AU. This comprised 59.5% of a total of 928 new patients diagnosed with uveitis from 2005 to 2010. The mean age was 48.0 ± 17.2 years. There was a male predominance (62.5%), with a male:female ratio of 1.7:1. The majority were of Chinese ethnicity (69%), followed by Malays (13.2%). Most cases were unilateral (79.5%) and idiopathic (50.4%). Common etiological causes included Fuchs heterochromic iridocyclitis (FHI) (5.6%), ankylosing spondylitis (AS)-related AU (5.1%), herpes simplex virus (HSV) (4.7%), and herpes zoster virus (HZV) (4.5%). There were increasing trends in AS-related AU from 3.2% in 2008 to 6.5% in 2010, and psoriasis-associated AU from 1.7% in 2005 to 4.0% in 2008. There were decreasing trends in the incidence of FHI from 10.6% in 2006 to 4.7% in 2009. No change in incidence of viral etiologies was noted, but cytomegalovirus-related immune-recovery uveitis (IRU) comprised 7.4%. IRU showed an increasing trend from 1.7% in 2005 to 11.9% in 2007, then decreased to 3.3% in 2010. Using the Pearson chi-square test, there was no statistically significant association between ethnicities (Chinese, Malay, Indian) comparing infectious and noninfectious cases (p = 0.788), idiopathic and nonidiopathic cases (p = 0.170), or between the various etiologies of uveitis (p = 0.168). AU was the predominant form of uveitis seen at our centers. Infectious etiologies (18.5%) are the most common among nonidiopathic cases, with herpes viruses (9.2%) being most prevalent. Despite increased use of polymerase chain reaction (PCR) in the detection of microbial and viral DNA, there was no overall increase in detection of infectious causes for

  11. Efficacy of immunomodulatory therapy with interferon-β or glatiramer acetate on multiple sclerosis-associated uveitis.

    PubMed

    Velazquez-Villoria, D; Macia-Badia, C; Segura-García, A; Pastor Idoate, S; Arcos-Algaba, G; Velez-Escola, L; García-Arumí, J

    2017-06-01

    To analyse the role of interferon-β or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. A study was conducted on a non-randomised, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-β or glatiramer acetate) to control the course of the multiple sclerosis. Patients were compared to themselves before initiating the treatment, in order to assess the difference in uveitis episodes. The main outcome measurements were the number of uveitis episodes with/without immunomodulatory treatment. Uveitis was bilateral in 10 (77%) out of 13 patients. Intermediate uveitis was observed in 11 patients, retinal vasculitis in 3 patients, and one patient was classified as a posterior uveitis. The patients had a mean of 4.15±3.1 episodes of uveitis (range 1-10) during the follow-up period (148.6±84.3 months). When compared to their pre-treatment status, patients on treatment with interferon-β or glatiramer acetate showed a significant decrease of 0.36 episodes of ocular inflammation per year (P=.02). Mild side effects related to immunomodulatory treatment were observed in 6 (46%) patients, 3 (23%) patients with a flu-like syndrome, and 3 (23%) patients with a skin rash. Interferon β or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis, and was well tolerated in most patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis

    PubMed Central

    Rosenbaum, J. T.; Landewé, R.; Marzo‐Ortega, H.; Sieper, J.; van der Heijde, D.; Davies, O.; Bartz, H.; Hoepken, B.; Nurminen, T.; Deodhar, A.

    2016-01-01

    Objective Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID‐axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. Methods The RAPID‐axSpA (NCT01087762) trial is double‐blind and placebo‐controlled to week 24, dose‐blind to week 48, and open‐label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose‐blind phase were re‐randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient‐years. Results At baseline, 38 of 218 CZP‐randomized patients (17.4%) and 31 of 107 placebo‐randomized patients (29.0%) had past uveitis history. During the 24‐week double‐blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6–8.8] per 100 patient‐years) than in placebo (10.3 [95% CI 2.8–26.3] per 100 patient‐years). All cases observed during the 24‐week double‐blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5–50.1] per 100 patient‐years) than placebo (38.5 [95% CI 10.5–98.5] per 100 patient‐years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2–7.4] per 100 patient‐years) and were similar between AS (4.4 [95% CI 2.3–7.7] per 100 patient‐years) and nr‐axial SpA (5.6 [95% CI 2.9–9.8] per 100 patient‐years). Conclusion The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported

  13. Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis.

    PubMed

    Rudwaleit, M; Rosenbaum, J T; Landewé, R; Marzo-Ortega, H; Sieper, J; van der Heijde, D; Davies, O; Bartz, H; Hoepken, B; Nurminen, T; Deodhar, A

    2016-06-01

    Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID-axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. The RAPID-axSpA (NCT01087762) trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose-blind phase were re-randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient-years. At baseline, 38 of 218 CZP-randomized patients (17.4%) and 31 of 107 placebo-randomized patients (29.0%) had past uveitis history. During the 24-week double-blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6-8.8] per 100 patient-years) than in placebo (10.3 [95% CI 2.8-26.3] per 100 patient-years). All cases observed during the 24-week double-blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5-50.1] per 100 patient-years) than placebo (38.5 [95% CI 10.5-98.5] per 100 patient-years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2-7.4] per 100 patient-years) and were similar between AS (4.4 [95% CI 2.3-7.7] per 100 patient-years) and nr-axial SpA (5.6 [95% CI 2.9-9.8] per 100 patient-years). The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti-tumor necrosis factor antibodies. © 2016, American College

  14. Anti-TNFα agents and methotrexate in spondyloarthritis related uveitis in a Chinese population.

    PubMed

    Lian, Fan; Zhou, Jun; Wei, Cui; Wang, Yu; Xu, Hanshi; Liang, Liuqin; Yang, Xiuyan

    2015-11-01

    This study seeks to evaluate the clinical characteristics of spondyloarthritis (SpA)-related uveitis in a cohort from South China and to assess the efficacy and safety of therapies based on TNF blockers. SpA patients with uveitis admitted to a south China hospital were enrolled. Demographic information, clinical characteristics, laboratory findings, intraocular inflammation, visual acuity, macular thickness, and treatments were documented. Of the 1,036 SpA patients reviewed, 182 had uveitis. Ankylosing spondylitis (AS) was the most common subtype. Unilateral uveitis was found in 51 cases (51/182, 28.0%), and unilateral alternating uveitis was found in 75 cases (75/182, 41.2%). Half of the cases were recurrent uveitis (52.2%), and acute onset was common (76.4%). The most serious complication was vision loss (0.5%). No significant difference in disease activity was found between the SpA patients with or without uveitis. Predominant improvements were found in cases treated with all three anti-TNFs (infliximab, adalimumab, and etanercept) and anti-TNFs plus methotrexate (MTX). Monotherapy of methotrexate was not adequate for inducing remission. Monotherapy of etanercept was not as effective as adalimumab and infliximab, mainly in the prevention of recurrence. No significant difference in effectiveness was found among the three anti-TNFs if MTX was added. Etanercept plus MTX were well tolerated. Infliximab and adalimumab were associated with more tuberculosis and/or hepatitis flares. Uveitis is common in SpA patients. Severe complications may develop in prolonged and intractable cases. Treatments based on anti-TNFs had good clinical response, and better safety documentation were observed in etanercept plus MTX compared to the other two anti-TNF monoclonal antibodies plus MTX.

  15. Infliximab Versus Adalimumab in the Treatment of Refractory Inflammatory Uveitis: A Multicenter Study From the French Uveitis Network.

    PubMed

    Vallet, Hélène; Seve, Pascal; Biard, Lucie; Baptiste Fraison, Jean; Bielefeld, Philip; Perard, Laurent; Bienvenu, Boris; Abad, Sébastien; Rigolet, Aude; Deroux, Alban; Sene, Damien; Perlat, Antoinette; Marie, Isabelle; Feurer, Elodie; Hachulla, Eric; Fain, Olivier; Clavel, Gaëlle; Riviere, Sophie; Bouche, Pierre-Alban; Gueudry, Julie; Pugnet, Gregory; Le Hoang, Phuc; Resche Rigon, Matthieu; Cacoub, Patrice; Bodaghi, Bahram; Saadoun, David

    2016-06-01

    To analyze the factors associated with response to anti-tumor necrosis factor (anti-TNF) treatment and compare the efficacy and safety of infliximab (IFX) and adalimumab (ADA) in patients with refractory noninfectious uveitis. This was a multicenter observational study of 160 patients (39% men and 61% women; median age 31 years [interquartile range 21-42]) with uveitis that had been refractory to other therapies, who were treated with anti-TNF (IFX 5 mg/kg at weeks 0, 2, 6, and then every 5-6 weeks [n = 98] or ADA 40 mg every 2 weeks [n = 62]). Factors associated with complete response were assessed by multivariate analysis. Efficacy and safety of IFX versus ADA were compared using a propensity score approach with baseline characteristics taken into account. Subdistribution hazard ratios (SHRs) and 95% confidence intervals (95% CIs) were calculated. The main etiologies of uveitis included Behçet's disease (BD) (36%), juvenile idiopathic arthritis (22%), spondyloarthropathy (10%), and sarcoidosis (6%). The overall response rate at 6 and 12 months was 87% (26% with complete response) and 93% (28% with complete response), respectively. The median time to complete response was 2 months. In multivariate analysis, BD and occurrence of >5 uveitis flares before anti-TNF initiation were associated with complete response to anti-TNF (SHR 2.52 [95% CI 1.35-4.71], P = 0.004 and SHR 1.97 [95% CI 1.02-3.84], P = 0.045, respectively). Side effects were reported in 28% of patients, including serious adverse events in 13%. IFX and ADA did not differ significantly in terms of occurrence of complete response (SHR 0.65 [95% CI 0.25-1.71], P = 0.39), serious side effects (SHR 0.22 [95% CI 0.04-1.25], P = 0.089), or event-free survival (SHR 0.55 [95% CI 0.28-1.08], P = 0.083). Anti-TNF treatment is highly effective in refractory inflammatory uveitis. BD is associated with increased odds of response. IFX and ADA appear to be equivalent in terms of efficacy.

  16. Pars Plana Vitrectomy for the Treatment of Uveitis.

    PubMed

    Henry, Christopher R; Becker, Matthias D; Yang, Yongsheng; Davis, Janet L

    2018-06-01

    To review and summarize evidence in the medical literature regarding the use of pars plana vitrectomy in the management of uveitis. Systematic literature review. A systematic literature search was conducted for relevant articles on pars plana vitrectomy for the management of uveitis. Results from the studies were compiled and analyzed. Thirty-four articles, published from 2005 through 2014, were included in the final data analysis. Thirty-two manuscripts were from retrospective case series and 2 manuscripts were from randomized pilot studies. The median Scottish Intercollegiate Guidelines Network level of evidence grade was 3 and the median Oxford Center for Evidence-based Medicine level of evidence grade was 4. Fewer than 50% of the articles in the current study applied Standardization of Uveitis Nomenclature (SUN) criteria in regard to reporting the anatomic location of uveitis, fewer than 25% of studies applied SUN criteria in regard to the reporting of anterior chamber cells before and after PPV, fewer than 10% of studies applied SUN criteria to the grading of anterior chamber flare before and after PPV, and fewer than 10% of studies applied standardized criteria to the grading of vitreous haze after PPV. Overall, 627 patients and 708 total eyes undergoing PPV for uveitis were included. The average reported age of all patients was 43.4 years. The median duration of uveitis prior to PPV reported in the studies was 36.1 months (range 4-198 months). The median follow-up after PPV reported in the studies was 18.9 months (range 2-114 months). Vision was reported for 519 eyes and was improved in 356 eyes (69%), unchanged in 95 eyes (18%), and worse in 68 eyes (13%) following PPV. Preoperatively, 157 of 300 (52%) eyes in these studies had documented cystoid macular edema compared to 112 of 300 (37%) postoperatively. Median use of oral corticosteroids improved from 48% preoperatively to 12% postoperatively among the reporting studies. Median use of other

  17. Chronic varied stress modulates experimental autoimmune encephalomyelitis in Wistar rats.

    PubMed

    Correa, S G; Rodriguez-Galán, M C; Rivero, V E; Riera, C M

    1998-06-01

    Stress disturbs homeostasis by altering the equilibrium of various hormones which have a significant impact on immune responses. Few studies have examined the influence of stressors on autoimmune disease in animal models. In our work, we studied the effects of long-term exposure (14 days) to chronic varied stress (CVS) in a model of experimental autoimmune encephalomyelitis (EAE) in Wistar rats. We studied whether the exposure to CVS before or after the immune challenge would correlate with differences in the clinical course of the disease. We also examined whether the CVS would modulate the magnitude of the cellular or the humoral immune response. We observed opposite effects on the clinical signs in animals stressed before or after the immune challenge. The clinical signs of the disease were attenuated in animals stressed before but not after the immune challenge. Relationships were found in the modulation of the clinical severity related to the time of exposure to the CVS, the histological alterations and the proliferative results. Stressed animals with milder clinical signs presented an exacerbated humoral response against myelin antigens while stressed animals with more severe clinical symptoms exhibited a significantly diminished one. Besides, we detected the presence of specific IgG1 associated with the exposure to CVS before the induction of EAE. Our results show that, depending on the timing of the exposure of Wistar rats to the CVS, the neuroendocrine disbalance favors a more pronounced humoral or cellular profile of the response.

  18. A systematic approach to emergencies in uveitis.

    PubMed

    Al-Dhibi, Hassan A; Al-Mahmood, Ammar M; Arevalo, J Fernando

    2014-01-01

    Uveitis is a common cause of preventable blindness although it is consider a sight-threatening condition particularly in cases with posterior segment inflammation. To deal with emergency conditions in uveitis, we must aware of the essential signs and symptoms that reflect a true uveitic emergency. Failure to recognize these essential signs and symptoms of a true uveitic emergency may result in a devastating visual outcome. This review provides general ophthalmologists and residents, clinical guidelines for the main uveitic entities that require immediate recognition and urgent intervention in the emergency room to prevent severe permanent visual loss.

  19. A Systematic Approach to Emergencies in Uveitis

    PubMed Central

    Al-Dhibi, Hassan A.; Al-Mahmood, Ammar M.; Arevalo, J. Fernando

    2014-01-01

    Uveitis is a common cause of preventable blindness although it is consider a sight-threatening condition particularly in cases with posterior segment inflammation. To deal with emergency conditions in uveitis, we must aware of the essential signs and symptoms that reflect a true uveitic emergency. Failure to recognize these essential signs and symptoms of a true uveitic emergency may result in a devastating visual outcome. This review provides general ophthalmologists and residents, clinical guidelines for the main uveitic entities that require immediate recognition and urgent intervention in the emergency room to prevent severe permanent visual loss. PMID:25100911

  20. Impact of pregabalin treatment on synaptic plasticity and glial reactivity during the course of experimental autoimmune encephalomyelitis

    PubMed Central

    Silva, Gleidy A A; Pradella, Fernando; Moraes, Adriel; Farias, Alessandro; dos Santos, Leonilda M B; de Oliveira, Alexandre L R

    2014-01-01

    Background Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that affects young adults. It is characterized by generating a chronic demyelinating autoimmune inflammation in the central nervous system. An experimental model for studying MS is the experimental autoimmune encephalomyelitis (EAE), induced by immunization with antigenic proteins from myelin. Aims The present study investigated the evolution of EAE in pregabalin treated animals up to the remission phase. Methods and results The results demonstrated a delay in the onset of the disease with statistical differences at the 10th and the 16th day after immunization. Additionally, the walking track test (CatWalk) was used to evaluate different parameters related to motor function. Although no difference between groups was obtained for the foot print pressure, the regularity index was improved post treatment, indicating a better motor coordination. The immunohistochemical analysis of putative synapse preservation and glial reactivity revealed that pregabalin treatment improved the overall morphology of the spinal cord. A preservation of circuits was depicted and the glial reaction was downregulated during the course of the disease. qRT-PCR data did not show immunomodulatory effects of pregabalin, indicating that the positive effects were restricted to the CNS environment. Conclusions Overall, the present data indicate that pregabalin is efficient for reducing the seriousness of EAE, delaying its course as well as reducing synaptic loss and astroglial reaction. PMID:25365796

  1. Dexamethasone intravitreal implant (Ozurdex) for the treatment of pediatric uveitis.

    PubMed

    Bratton, Monica L; He, Yu-Guang; Weakley, David R

    2014-04-01

    To report our experience using Ozurdex (Allergan, Irvine, CA), a biodegradable intravitreal implant containing of 0.7 mg of dexamethasone approved for use in adults with noninfectious uveitis in adults, in the treatment of pediatric uveitis. The medical records of consecutive patients with noninfectious posterior uveitis who were unresponsive to standard treatment and subsequently received the Ozurdex implant from March 2011 to March 2013 were retrospectively reviewed. A total of 14 eyes of 11 patients (mean age, 10.1 years; range 4-12) received 22 Ozurdex implants during the study period. Of the 11 patients, 7 had idiopathic intermediate or posterior uveitis, 1 had sympathetic ophthalmia, 2 had juvenile idiopathic arthritis, and 1 had sarcoidosis. All patients were uncontrolled with standard treatment, including topical or sub-Tenon's or systemic corticosteriods and/or immune-modulation. Visual acuity improved after Ozurdex implant in 5 of 8 patients (63%). Intraocular inflammation was controlled or improved after 17 of 22 of implants (12 eyes [77%]). The frequency of topical corticosteroids was decreased and/or discontinued after 18 of 22 implants (12 eyes [82%]). Complications included implant migration into the anterior chamber (4 aphakic eyes), increased intraocular pressure (5 eyes), and progression of a preexisting cataract (1 eye). The uveitis reoccurred in 57% of eyes at 4.3 months (2-7 months) after injection. The Ozurdex implant in combination with systemic immunomodulatory therapy resulted in improved visual acuity, control of intraocular inflammation, and a decrease in corticosteroid use. In the majority of eyes the uveitis reoccurred around 4 months after injection. The adverse events in our study are similar to those identified in adult studies. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  2. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop.

    PubMed

    Jabs, Douglas A; Nussenblatt, Robert B; Rosenbaum, James T

    2005-09-01

    To begin a process of standardizing the methods for reporting clinical data in the field of uveitis. Consensus workshop. Members of an international working group were surveyed about diagnostic terminology, inflammation grading schema, and outcome measures, and the results used to develop a series of proposals to better standardize the use of these entities. Small groups employed nominal group techniques to achieve consensus on several of these issues. The group affirmed that an anatomic classification of uveitis should be used as a framework for subsequent work on diagnostic criteria for specific uveitic syndromes, and that the classification of uveitis entities should be on the basis of the location of the inflammation and not on the presence of structural complications. Issues regarding the use of the terms "intermediate uveitis," "pars planitis," "panuveitis," and descriptors of the onset and course of the uveitis were addressed. The following were adopted: standardized grading schema for anterior chamber cells, anterior chamber flare, and for vitreous haze; standardized methods of recording structural complications of uveitis; standardized definitions of outcomes, including "inactive" inflammation, "improvement'; and "worsening" of the inflammation, and "corticosteroid sparing," and standardized guidelines for reporting visual acuity outcomes. A process of standardizing the approach to reporting clinical data in uveitis research has begun, and several terms have been standardized.

  3. [Vision-and health-related quality of life in patients with uveitis].

    PubMed

    Zhang, J; Yan, H G; Chi, Y; Guo, C Y; Yang, L

    2016-06-11

    To evaluate vision-and health-related quality of life in patients with uveitis, and to evaluate the relationship between quality of life and visual acuity. Cross-sectional study. One hundred and eleven patients with uveitis were enrolled in the study from January 1, 2013 to April 1, 2014 in Peking University First Hospital. Clinical data collected included medical history, complete ophthalmologic examination and best corrected visual acuity (LogMAR). Basic clinical data (gender, diagnosis, etc.) was also collected. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and the 36-Item Short Form Health Survey (SF-36) were administered. The patients were divided into two groups, anterior uveitis group (ATU), and other types of uveitis in this study (OTU). T-test was used for analysis of the data which obey standard normal distribution, otherwise rank sum test was used for data analysis. Correlation and Linear regression were constructed between bilateral visual acuity and the scores of NEI VFQ-25 and SF-36 questionnaires. For all the 111 cases included in this study, 87 (78.4%) of them were anterior uveitis (ATU), 5 of them were intermediate uveitis, 7 of them were posterior uveitis and 12 of them were pan uveitis. Mean visual acuity of better and worse eye were 0.0 and 0.2 in ATU patients, respectively. Mean visual acuity of better and worse eye were 0.1 and 0.4 in OTU patients, respectively. Patients rated the general health subscale score of NEI VFQ-25 and SF-36 lower than other subscales, respectively (score of general health was 25.0 (25.0-50.0) in NEI VFQ-25 and 46.8 (19.8) in SF-36). ATU group scored higher that OTU group (Mean score of SF-36 was 77.5 (10.7) and 68.8 (16.9) in ATU and OTU group respectively, P value of SF-36< 0.01, t=9.54. Mean score of NEI VFQ-25 was 77.3 (12.8) and 59.1 (16.5) in ATU and OTU group respectively, P value of NEI VFQ-25<0.01, t=33.16). Mean score of NEI VFQ-25 of all patients was 73.4 (15.5). Mean visual

  4. Methotrexate therapy may prevent the onset of uveitis in juvenile idiopathic arthritis.

    PubMed

    Papadopoulou, Charalampia; Kostik, Mikhail; Böhm, Marek; Nieto-Gonzalez, Juan Carlos; Gonzalez-Fernandez, Maria Isabel; Pistorio, Angela; Martini, Alberto; Ravelli, Angelo

    2013-09-01

    To evaluate whether early treatment with methotrexate (MTX) prevents the onset of uveitis in children with juvenile idiopathic arthritis. The clinical charts of all consecutive patients seen between January 2002 and February 2011 who had a disease duration <1 year at first visit and had received a stable management for at least 2 years with or without MTX were reviewed. Patients who were given systemic medications other than MTX (except nonsteroidal anti-inflammatory drugs) were excluded. Patients with systemic arthritis, rheumatoid factor-positive arthritis, or enthesitis-related arthritis were also excluded. In each patient, the 2-year follow-up period after first visit was examined to establish whether uveitis had occurred. A total of 254 patients with a median disease duration of 0.3 year were included. Eighty-six patients (33.9%) were treated with MTX, whereas 168 patients (66.1%) did not receive MTX. During the 2-year follow-up, 211 patients (83.1%) did not develop uveitis, whereas 43 patients (16.9%) had uveitis a median of 1.0 year after the first visit. The frequency of uveitis was lower in MTX-treated than in MTX-untreated patients (10.5% vs 20.2%, respectively, P = .049). Survival analysis confirmed that patients treated with MTX had a lower probability of developing uveitis. Early MTX therapy may prevent the onset of uveitis in children with juvenile idiopathic arthritis. Because our study may be affected by confounding by indication, the potential of MTX to reduce the incidence of ocular disease should be investigated in a randomized controlled trial. Copyright © 2013 Mosby, Inc. All rights reserved.

  5. Cutting Edge: Nanogel-Based Delivery of an Inhibitor of CaMK4 to CD4+ T Cells Suppresses Experimental Autoimmune Encephalomyelitis and Lupus-like Disease in Mice.

    PubMed

    Otomo, Kotaro; Koga, Tomohiro; Mizui, Masayuki; Yoshida, Nobuya; Kriegel, Christina; Bickerton, Sean; Fahmy, Tarek M; Tsokos, George C

    2015-12-15

    Treatment of autoimmune diseases is still largely based on the use of systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV is involved in the suppression of IL-2 and the production of IL-17. Its pharmacologic or genetic inhibition limits autoimmune disease in mice. In this study, we demonstrate that KN93, a small-molecule inhibitor of calcium/calmodulin-dependent protein kinase IV, targeted to CD4(+) T cells via a nanolipogel delivery system, markedly reduced experimental autoimmune encephalomyelitis and was 10-fold more potent than the free systemically delivered drug in the lupus mouse models. The targeted delivery of KN93 did not deplete T cells but effectively blocked Th17 cell differentiation and expansion as measured in the spinal cords and kidneys of mice developing experimental autoimmune encephalomyelitis or lupus, respectively. These results highlight the promise of cell-targeted inhibition of molecules involved in the pathogenesis of autoimmunity as a means of advancing the treatment of autoimmune diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

  6. Rubella Virus-associated Anterior Uveitis in a Vaccinated Patient: A Case Report.

    PubMed

    ten Berge, Josianne C E M; van Daele, Paul L A; Rothova, Aniki

    2016-01-01

    Rubella virus is involved in the pathogenesis of Fuchs heterochromic uveitis and almost all cases in Europe show an active antibody production in the aqueous humor against rubella virus. Herein we report a case of a fully vaccinated patient with common variable immunodeficiency who developed unilateral Fuchs heterochromic uveitis secondary to rubella virus which was proven by intraocular fluid examination. Awareness of rubella associated anterior uveitis should remain also in vaccinated patients, especially those without a fully competent immune system.

  7. Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate.

    PubMed

    Foster, C Stephen; Tufail, Fehma; Waheed, Nadia Khalida; Chu, David; Miserocchi, Elisabetta; Baltatzis, Stefanos; Vredeveld, Cindy M

    2003-04-01

    To evaluate the efficacy of etanercept vs placebo in preventing relapses of uveitis in patients taking methotrexate with control of uveitis and whose methotrexate dosage was being tapered. Patients with chronic or recurrent noninfectious uveitis with inflammation controlled by low-dose methotrexate were randomized to either the drug or placebo group in a double-masked manner, given a methotrexate taper schedule, and followed for 24 weeks. The main outcome measures were control of inflammation, visual acuity, and adverse reactions. Data were analyzed both as an attempt-to-treat analysis and an analysis only of those patients who completed the study. A total of 20 patients were randomized to the drug and placebo groups. Relapse of uveitis occurred in 3 of 10 patients in the treatment group and 5 of 10 patients in the control group. Two patients in the treatment group withdrew prematurely from the study due to adverse effects. There was no significant difference between the treatment and placebo groups with regard to the rate of relapse and the final visual acuity. No patient suffered from any irreversible, long-term morbidity or mortality. Etanercept has no significant efficacy over placebo in preventing relapses of uveitis in patients being tapered from methotrexate.

  8. A pre- and post-treatment evaluation of vision-related quality of life in uveitis

    PubMed Central

    Rathinam, SR

    2008-01-01

    Aim: To study the effect of treatment on vision-related quality of life (VR-QOL) in uveitis patients. Materials and Methods: Interviewer-administered questionnaire-based evaluation of visual function and VR-QOL in Tamil-speaking adult patients with active uveitis at presentation and follow-up by the same interviewer. Results: Ninety-eight patients participated in this study. There was a statistically significant improvement in VR-QOL in all the scales following treatment (P < 0.001). Patients with chronic uveitis showed better improvement upon treatment than patients with acute uveitis. The visual symptoms scale showed moderate gains following treatment (effect size 0.56). Persons with bilateral disease had poorer mean scores compared to those with unilateral disease. Visual acuity was closely correlated with VR-QOL scores. Conclusion: The VR-QOL measurement has shown that it is sensitive to demonstrate the problems of patients with uveitis irrespective of their demographic profile. The scores improved significantly in patients with uveitis following treatment and have shown close correlation to visual acuity thus demonstrating that VR-QOL is effective in assessing the response to treatment. PMID:18579990

  9. Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus.

    PubMed

    Bou, Rosa; Adán, Alfredo; Borrás, Fátima; Bravo, Beatriz; Calvo, Inmaculada; De Inocencio, Jaime; Díaz, Jesús; Escudero, Julia; Fonollosa, Alex; de Vicuña, Carmen García; Hernández, Victoria; Merino, Rosa; Peralta, Jesús; Rúa, María-Jesús; Tejada, Pilar; Antón, Jordi

    2015-05-01

    Uveitis associated with juvenile idiopathic arthritis (JIA) typically involves the anterior chamber segment, follows an indolent chronic course, and presents a high rate of uveitic complications and a worse outcome as compared to other aetiologies of uveitis. Disease assessment, treatment, and outcome measures have not been standardized. Collaboration between pediatric rheumatologists and ophthalmologists is critical for effective management and prevention of morbidity, impaired vision, and irreparable visual loss. Although the Standardization of Uveitis Nomenclature Working Group recommendations have been a great advance to help clinicians to improve consistency in grading and reporting data, difficulties arise at the time of deciding the best treatment approach in the individual patient in routine daily practice. For this reason, recommendations for a systematized control and treatment strategies according to clinical characteristics and disease severity in children with JIA-related uveitis were developed by a panel of experts with special interest in uveitis associated with JIA. A clinical management algorithm organized in a stepwise regimen is here presented.

  10. OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages

    PubMed Central

    D’Souza, Cheryl A.; Zhao, Fei Linda; Li, Xujian; Xu, Yan; Dunn, Shannon E.; Zhang, Li

    2016-01-01

    Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity. PMID:26828924

  11. Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.

    PubMed

    Stanisavljević, Suzana; Dinić, Miroslav; Jevtić, Bojan; Đedović, Neda; Momčilović, Miljana; Đokić, Jelena; Golić, Nataša; Mostarica Stojković, Marija; Miljković, Đorđe

    2018-01-01

    Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.

  12. Retinal pigmentary changes in chronic uveitis mimicking retinitis pigmentosa.

    PubMed

    Sevgi, D Damla; Davoudi, Samaneh; Comander, Jason; Sobrin, Lucia

    2017-09-01

    To present retinal pigmentary changes mimicking retinitis pigmentosa (RP) as a finding of advanced uveitis. We retrospectively reviewed charts of patients without a family history of inherited retinal degenerations who presented with retinal pigment changes and signs of past or present intraocular inflammation. Comprehensive eye examination including best-corrected visual acuity, slit-lamp examination and dilated fundus examination was performed on all patients in addition to color fundus photography, optical coherence tomography, fluorescein angiography (FA), and full-field electroretinogram testing. We identified five patients with ages ranging from 33 to 66 years, who presented with RP-like retinal pigmentary changes which were eventually attributed to longstanding uveitis. The changes were bilateral in three cases and unilateral in two cases. Four of five cases presented with active inflammation, and the remaining case showed evidence of active intraocular inflammation during follow-up. This study highlights the overlapping features of advanced uveitis and RP including the extensive pigmentary changes. Careful review of possible past uveitis history, detailed examination of signs of past or present inflammation and ancillary testing, with FA often being most helpful, are required for the correct diagnosis. This is important, because intervention can prevent further damage if the cause of the pigmentary changes is destructive inflammation.

  13. Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.

    PubMed

    Jackson, Christopher M; Flies, Dallas B; Mosse, Claudio A; Parwani, Anil; Hipkiss, Edward L; Drake, Charles G

    2013-05-01

    Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. Copyright © 2012 Wiley Periodicals, Inc.

  14. Strain-Specific Induction of Experimental Autoimmune Prostatitis (EAP) in Mice

    PubMed Central

    Jackson, Christopher M.; Flies, Dallas B.; Mosse, Claudio A.; Parwani, Anil; Hipkiss, Edward L.; Drake, Charles G.

    2013-01-01

    BACKGROUND Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. METHODS Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. RESULTS In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. CONCLUSIONS These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. PMID:23129407

  15. BIRC4 Mutation: An Important Rare Cause of Uveitis.

    PubMed

    Basiaga, Matthew L; Weiss, Pamela F; Behrens, Edward M

    2015-12-01

    We report a 6-year-old man with chronic severe recalcitrant bilateral anterior uveitis and a remote history of hemophagocytic lymphocytic histiocytosis secondary to Epstein-Barr virus infection. The patient was treated for idiopathic uveitis after an initial extensive evaluation failed to reveal a specific diagnosis. The patient failed to achieve sustained inactive disease with multiple monotherapies including topical glucocorticoid, methotrexate, infliximab, mycophenolate mofeti, and cyclosporine. Disease control was finally attained with a combination of cyclosporine and adalimumab. After more recent testing, he was found to have a novel deletion on the BIRC4 (baclovirus inhibitor of apoptosis repeat containing protein 4) gene, the causative gene for X-linked lymphoproliferative syndrome type 2. We conclude that male patients with chronic idiopathic uveitis should be questioned about a history of hemophagocytic lymphocytic histiocytosis during their workup and screened for BIRC4 mutation if appropriate.

  16. Fluorescein and Indocyanine Green Angiography for Uveitis

    PubMed Central

    Herbort, Carl P

    2009-01-01

    In recent years enormous progress has been achieved in investigational procedures for uveitis. Imaging is one such example with the advent of new methods such as indocyanine green angiography, ultrasound biomicroscopy and optical coherence tomography to cite only the most important. This tremendous increase in precision and accuracy in the assessment of the level and degree of inflammation and its monitoring comes in parallel with the development of extremely potent and efficacious therapies. In view of these developments, our whole attitude in the appraisal and investigation of the uveitis patient has to be adapted and correctly reoriented integrating the recent developments and this is no different for ocular angiography. PMID:20404985

  17. Protein kinase Cβ as a therapeutic target stabilizing blood–brain barrier disruption in experimental autoimmune encephalomyelitis

    PubMed Central

    Lanz, Tobias V.; Becker, Simon; Osswald, Matthias; Bittner, Stefan; Schuhmann, Michael K.; Opitz, Christiane A.; Gaikwad, Sadanand; Wiestler, Benedikt; Litzenburger, Ulrike M.; Sahm, Felix; Ott, Martina; Iwantscheff, Simeon; Grabitz, Carl; Mittelbronn, Michel; von Deimling, Andreas; Winkler, Frank; Meuth, Sven G.; Wick, Wolfgang; Platten, Michael

    2013-01-01

    Disruption of the blood–brain barrier (BBB) is a hallmark of acute inflammatory lesions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis. This disruption may precede and facilitate the infiltration of encephalitogenic T cells. The signaling events that lead to this BBB disruption are incompletely understood but appear to involve dysregulation of tight-junction proteins such as claudins. Pharmacological interventions aiming at stabilizing the BBB in MS might have therapeutic potential. Here, we show that the orally available small molecule LY-317615, a synthetic bisindolylmaleimide and inhibitor of protein kinase Cβ, which is clinically under investigation for the treatment of cancer, suppresses the transmigration of activated T cells through an inflamed endothelial cell barrier, where it leads to the induction of the tight-junction molecules zona occludens-1, claudin 3, and claudin 5 and other pathways critically involved in transendothelial leukocyte migration. Treatment of mice with ongoing experimental autoimmune encephalomyelitis with LY-317615 ameliorates inflammation, demyelination, axonal damage, and clinical symptoms. Although LY-317615 dose-dependently suppresses T-cell proliferation and cytokine production independent of antigen specificity, its therapeutic effect is abrogated in a mouse model requiring pertussis toxin. This abrogation indicates that the anti-inflammatory and clinical efficacy is mainly mediated by stabilization of the BBB, thus suppressing the transmigration of encephalitogenic T cells. Collectively, our data suggest the involvement of endothelial protein kinase Cβ in stabilizing the BBB in autoimmune neuroinflammation and imply a therapeutic potential of BBB-targeting agents such as LY-317615 as therapeutic approaches for MS. PMID:23959874

  18. Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis.

    PubMed

    Puchta, Joachim; Hattenbach, Lars-Olof; Baatz, Holger

    2005-01-01

    To determine the intraocular levels of methotrexate in low-dose treatment of noninfectious uveitis. One day after oral administration, the methotrexate level was measured in the aqueous humor and serum of a patient with noninfectious uveitis, who underwent cataract surgery. A fluorescence polarization immunoassay was used for determination. After oral administration, methotrexate was only measurable in aqueous humor but not in serum. In uveitis, orally administered low-dose methotrexate reaches detectable levels in aqueous humor, even in the absence of detectable levels in serum. Copyright (c) 2005 S. Karger AG, Basel.

  19. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice.

    PubMed

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-11-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.

  20. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

    PubMed Central

    Pasadhika, Sirichai; Rosenbaum, James T

    2014-01-01

    Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

  1. Vaccines, adjuvants and autoimmunity.

    PubMed

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Off-Label Uses of Anti-TNF Therapy in Three Frequent Disorders: Behçet's Disease, Sarcoidosis, and Noninfectious Uveitis

    PubMed Central

    Sánchez-Cano, Daniel; Callejas-Rubio, José Luis; Ruiz-Villaverde, Ricardo; Ríos-Fernández, Raquel; Ortego-Centeno, Norberto

    2013-01-01

    Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series. PMID:23983404

  3. Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring.

    PubMed

    Cho, Heeyoon; Pillai, Parvathy; Nicholson, Laura; Sobrin, Lucia

    2016-01-01

    To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100% and 86.9-100% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 µm (p = 0.01). Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis.

  4. Clinical manifestations in uveitis patients with and without rheumatic disease in a Chinese population in Taiwan.

    PubMed

    Tseng, Shi-Ting; Yao, Tsung-Chieh; Huang, Jing-Long; Yeh, Kuo-Wei; Hwang, Yih-Shiou

    2017-12-01

    Uveitis can be a local eye disease or a manifestation of systemic rheumatologic disorders. However, the differences of clinical manifestations between uveitis patients with or without systemic rheumatologic disease have been seldom described in literature. We investigated the clinical features and complications of rheumatic disease-related uveitis, and compared the characteristics in patients with and without rheumatic disease in a Chinese population in Taiwan. A retrospective review was performed for all patients who had been diagnosed with uveitis between January 2009 and June 2014 at the Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. A total of 823 uveitis patients were enrolled in the study, including 123 patients with rheumatic diseases. The most frequent rheumatic diseases included ankylosing spondylitis (5.8%), followed by Behçet's disease (2.8%), sarcoidosis (1.4%), psoriasis (1.1%), and juvenile idiopathic arthritis (1.1%). Compared with patients without rheumatic disease, those with rheumatic disease-related uveitis had a lower mean age at onset (35.1 ± 15.8 years vs. 44.0 ± 17.5 years), a longer follow-up period (27.1 ± 25.3 months vs. 22.2 ± 23.0 months), a higher incidence of anterior uveitis (69.0% vs. 46.3%), less frequent posterior uveitis (4.9% vs. 21.4%), a higher incidence of recurrence (26.8% vs. 14.1%), more frequent bilateral involvement (53.7% vs. 38.8%), and more frequent posterior synechiae (17.2% vs. 9.4%). The disease course and clinical manifestations of rheumatic disease-related uveitis were different from those unrelated. Patients with rheumatic disease-related uveitis had a higher recurrent rate and more frequent posterior synechiae than patients without rheumatic diseases. Copyright © 2015. Published by Elsevier B.V.

  5. Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis.

    PubMed

    Goebel, J C; Roesel, M; Heinz, C; Michels, H; Ganser, G; Heiligenhaus, A

    2011-02-01

    To investigate the therapeutic value of azathioprine as monotherapy or combined with other immunosuppressive drugs for uveitis in patients with juvenile idiopathic arthritis (JIA). A retrospective multicentre study including 41 children with JIA (28 (68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis. Azathioprine was used to treat uveitis that was active in patients receiving topical or systemic corticosteroids, methotrexate or other immunosuppressive drugs. The primary end point was assessment of uveitis inactivity. Secondary end points comprised dose sparing of topical steroids and systemic corticosteroids, and immunosuppression. At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as combination therapy. During the entire azathioprine treatment period (mean 26 months), inactivity was obtained in 16/26 patients (61.5%) with monotherapy and in 10/15 (66.7%) when combined with other immunosuppressives (p=1.0). With azathioprine, dosages of systemic immunosuppression and steroids could be reduced by ≥ 50% (n=12) or topical steroids reduced to ≤ 2 drops/eye/day in six patients. In three patients (7.3%), azathioprine was discontinued because of nausea and stomach pain. Conclusions Azathioprine may be reconsidered in the stepladder approach for the treatment of JIA-associated uveitis. The addition of azathioprine may also be beneficial for patients not responding properly to methotrexate.

  6. Long-term efficacy of abatacept in pediatric patients with idiopathic uveitis: a case series.

    PubMed

    Marrani, Edoardo; Paganelli, Valeria; de Libero, Cinzia; Cimaz, Rolando; Simonini, Gabriele

    2015-10-01

    Non-infectious uveitis represents one of the most common causes of blindness, even at pediatric age; in particular, idiopathic chronic uveitis can pose significant difficulties during treatment, due to a partial response to TNF-α antagonists. To date, very few case series exist describing the treatment of idiopathic uveitis not adequately controlled by TNF-α antagonists. The aim of our study is to describe the role of abatacept in achieving remission in patients with idiopathic uveitis previously treated with TNF-α antagonists, and to assess how long abatacept efficacy is maintained during follow-up. The treatment's safety profile and tolerability were also specifically investigated. Three patients affected with chronic idiopathic uveitis, who have been treated with abatacept due to loss of efficacy of TNF-α antagonists, were reviewed. Details of the demographic and clinical characteristics were recorded, and a summary of the medical history was obtained. Patients were regularly reviewed in the ophthalmology and rheumatology clinics. Assessment of their ocular condition was characterized according to the Standardization of Uveitis Nomenclature (SUN) group. In our patients, abatacept was able to induce remission and to discontinue systemic corticosteroids after a mean of 30 weeks; the drug maintained its efficacy through a long follow-up period (42, 33, and 18 months respectively), with an excellent safety profile. Our small case series seems to suggest abatacept to be a promising therapy in children affected with chronic idiopathic uveitis not adequately controlled by TNF-α antagonists.

  7. Uveitis Reactivation in Children Treated with Tumor Necrosis Factor-α Inhibitors

    PubMed Central

    Lerman, Melissa A.; Lewen, Michael D.; Kempen, John H.; Mills, Monte D.

    2016-01-01

    PURPOSE To evaluate reactivation of pediatric uveitis during/following treatment with TNF-alpha inhibition (anti-TNFα). DESIGN Retrospective cohort study. METHODS We assessed the incidence of uveitis reactivation in children ≤18 years who had achieved uveitis quiescence under anti-TNFα. Survival analysis was used to calculate reactivation rates while still on (primary outcome), and following discontinuation of (secondary outcome), anti-TNFα. Potential predictive factors were assessed. RESULTS Among 50 children observed to develop quiescence of uveitis under anti-TNFα, 39 met criteria to be “at risk” of the primary (19 for the secondary) outcome. 60% were female, ~half had Juvenile Idiopathic Arthritis, and most were treated with infliximab. Overall, the estimated proportion relapsing within 12 months was 27.8% (95% confidence interval [CI]: 15.9-45.8%); the estimated probability of reactivation was higher following (63.8% [95% CI: 38.9-87.7%]), than before (21.6% [95% CI: 10.8-40.2%]), anti-TNFα discontinuation. Amongst those who discontinued anti-TNFα, the likelihood of reactivation was higher for those treated with adalimumab vs. infliximab (Hazard Ratio [HR] 13.4, p=0.01, 95% CI: 2.2-82.5) and those with older age at uveitis-onset (HR 1.3, p=0.09, 95% CI: 1.0-1.7). The duration of suppression, on medication, did not significantly affect the likelihood of reactivation when quiescence was maintained for ≥1.5 years. CONCLUSIONS Approximately 75% of children remaining on anti-TNFα following achievement of uveitis quiescence remain quiescent at one year. However, most reactivate following anti-TNFα discontinuation. These results suggest that infliximab more often is followed by remission, off medication, than adalimumab. The data do not suggest that maintenance of suppression, for more than 1.5 years decreases the reactivation risk. PMID:25892124

  8. Uveitis in patients with late-stage cutaneous melanoma treated with vemurafenib.

    PubMed

    Guedj, Mikael; Quéant, Astrid; Funck-Brentano, Elisa; Kramkimel, Nora; Lellouch, Judith; Monnet, Dominique; Longvert, Christine; Gantzer, Amelie; Brézin, Antoine P

    2014-12-01

    This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma. To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy. In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital. Patients' demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced. Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients. This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients' survival were greater than the risk to their

  9. Tubulointerstitial Nephritis and Uveitis Syndrome in a Twelve-Year-Old Girl

    PubMed Central

    Paladini, Alessia; Venturoli, Vittorio; Mosconi, Giovanni; Zambianchi, Loretta; Serra, Luigi; Valletta, Enrico

    2013-01-01

    Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder defined by the combination of biochemical abnormalities, tubulointerstitial nephritis, and uveitis. We describe a 12-year-old female, presented with a ten-day history of fever, characterized by sudden onset and rapid spontaneous resolution in few hours, accompanied by shivering, extreme fatigue, and loss of appetite. Laboratory values were consistent with renal failure of tubular origin. Renal biopsy confirmed a tubulointerstitial nephritis, with acute tubulitis, polymorphonuclear infiltration, and microabscesses. The renal interstitium was occupied by a dense inflammatory infiltrate, consisting of lymphocytes, plasma cells, and neutrophils. Glomerular structures were preserved. Ophthalmological examination that suggested a previous asymptomatic bilateral uveitis and HLA typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) further supported the suspect of TINU syndrome. TINU syndrome is probably an underdiagnosed disorder, responsible for many cases of idiopathic anterior uveitis in young patients, especially in those who have asymptomatic renal disease and when proper diagnostic tests are not performed at the time of presentation. PMID:23691408

  10. Tubulointerstitial nephritis and uveitis syndrome in a twelve-year-old girl.

    PubMed

    Paladini, Alessia; Venturoli, Vittorio; Mosconi, Giovanni; Zambianchi, Loretta; Serra, Luigi; Valletta, Enrico

    2013-01-01

    Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder defined by the combination of biochemical abnormalities, tubulointerstitial nephritis, and uveitis. We describe a 12-year-old female, presented with a ten-day history of fever, characterized by sudden onset and rapid spontaneous resolution in few hours, accompanied by shivering, extreme fatigue, and loss of appetite. Laboratory values were consistent with renal failure of tubular origin. Renal biopsy confirmed a tubulointerstitial nephritis, with acute tubulitis, polymorphonuclear infiltration, and microabscesses. The renal interstitium was occupied by a dense inflammatory infiltrate, consisting of lymphocytes, plasma cells, and neutrophils. Glomerular structures were preserved. Ophthalmological examination that suggested a previous asymptomatic bilateral uveitis and HLA typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) further supported the suspect of TINU syndrome. TINU syndrome is probably an underdiagnosed disorder, responsible for many cases of idiopathic anterior uveitis in young patients, especially in those who have asymptomatic renal disease and when proper diagnostic tests are not performed at the time of presentation.

  11. Acute anterior uveitis as the initial presentation of alkaptonuria.

    PubMed

    John, S S; Padhan, P; Mathews, J V; David, S

    2009-01-01

    Alkaptonuria is a rare autosomal recessive metabolic disorder that may present with multi-system involvement such as ochronotic arthropathy, renal, urethral and prostatic calculi, cardiac valvular lesions and pigmentation of the skin, sclera, cartilage and other connective tissues. An association of the disease with uveitis has never been reported. We report the first case of alkaptonuria with ochronotic arthropathy presenting with recurrent acute anterior uveitis as the initial manifestation. The possible common link with the HLA-B27 gene is discussed.

  12. Evidence for Tocilizumab as a Treatment Option in Refractory Uveitis Associated with Juvenile Idiopathic Arthritis.

    PubMed

    Tappeiner, Christoph; Mesquida, Marina; Adán, Alfredo; Anton, Jordi; Ramanan, Athimalaipet V; Carreno, Ester; Mackensen, Friederike; Kotaniemi, Kaisu; de Boer, Joke H; Bou, Rosa; de Vicuña, Carmen García; Heiligenhaus, Arnd

    2016-12-01

    To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy. A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit. TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.

  13. Current evidence of methotrexate efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach.

    PubMed

    Simonini, Gabriele; Paudyal, Priyamvada; Jones, Gareth T; Cimaz, Rolando; Macfarlane, Gary J

    2013-05-01

    To summarize evidence regarding the effectiveness of MTX in the treatment of childhood autoimmune chronic uveitis (ACU). A systematic search of articles between January 1990 and June 2011 was conducted using EMBASE, Ovid MEDLINE, Evidence-Based Medicine Reviews-ACP Journal Club, the Cochrane Library and EBM Reviews. Studies investigating the efficacy of MTX as a single immunosuppressant medication in the treatment of ACU refractory to therapy with topical treatment and/or systemic treatment in children (≤16 years) were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, expressed as Tyndall, as defined by the Standardization of Uveitis Nomenclature working group criteria. The effect measure for each study was the proportion of people classified as responders. We determined a combined estimate of the proportion of children in the eligible studies responding to MTX. The initial search identified 246 articles of which 52 were potentially eligible. Nine eligible articles, all retrospective chart reviews, remained in the analysis. The number of children in studies ranged from 3 to 25, and the dose of MTX varied from 7.5 to 30 mg/m2. Altogether, 95 of 135 children responded to MTX. The pooled analysis suggested that MTX has a favourable effect in the improvement of intraocular inflammation: the proportion of responding subjects was 0.73 (95% CI 0.66, 0.81). Although randomized controlled trials are needed, the available evidence supports the use of MTX in the treatment of childhood ACU: approximately three-quarters of patients on MTX can expect improvement in intraocular inflammation.

  14. Effect of an intravitreal cyclosporine implant on experimental uveitis in horses.

    PubMed

    Gilger, B C; Malok, E; Stewart, T; Horohov, D; Ashton, P; Smith, T; Jaffe, G J; Allen, J B

    2000-10-31

    The purpose of this study was to determine the effects of an intravitreal device releasing cyclosporine A (CsA) on recurrent inflammatory episodes in experimental uveitis. Nine normal horses were immunized peripherally with H37RA-mTB antigen twice, and then received 25 microg of H37RA-mTB antigen intravitreally in the right eye and an equal volume of balanced salt solution intravitreally in the left eye. Two weeks later, the animals randomly received either a CsA or a polymer implant (without CsA) in both eyes 1 week following implantation of the devices, 25 microg of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammation were graded following injections and implantation. The animals from each group were euthanized at 3, 14, and 28 days following the second injection. Aqueous and vitreous humor protein concentrations were measured. The presence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells and amount of tissue destruction were determined. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed for equine specific interleukin (IL) 2 and 4, interferon-gamma (IFN gamma) and beta-actin. In addition, aqueous and vitreous humor and peripheral blood were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4h of the first intravitreal H37RA-mTB antigen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous flare, myosis, and vitreous opacity. The severity of signs peaked 48 to 72 h after injection and subsequently decreased back to normal within 14 days. Following the second injection, clinical signs in the eyes with the CsA device were less severe and significantly shorter in duration than signs with the polymer only implant eyes. Aqueous and vitreous humor protein levels, infiltrating cell numbers, total number of T-lymphocytes, and levels of IL-2 and IFN gamma-mRNA were

  15. Cataract Surgery Outcomes in Uveitis: The Multicenter Uveitis Steroid Treatment Trial.

    PubMed

    Sen, H Nida; Abreu, Francis M; Louis, Thomas A; Sugar, Elizabeth A; Altaweel, Michael M; Elner, Susan G; Holbrook, Janet T; Jabs, Douglas A; Kim, Rosa Y; Kempen, John H

    2016-01-01

    To assess the visual outcomes of cataract surgery in eyes that received fluocinolone acetonide implant or systemic therapy with oral corticosteroids and immunosuppression during the Multicenter Uveitis Steroid Treatment (MUST) Trial. Nested prospective cohort study of patients enrolled in a randomized clinical trial. Patients that underwent cataract surgery during the first 2 years of follow-up in the MUST Trial. Visual outcomes of cataract surgery were evaluated 3, 6, and 9 months after surgery using logarithmic visual acuity charts. Change in visual acuity over time was assessed using a mixed-effects model. Best-corrected visual acuity. After excluding eyes that underwent cataract surgery simultaneously with implant surgery, among the 479 eyes in the MUST Trial, 117 eyes (28 eyes in the systemic, 89 in the implant group) in 82 patients underwent cataract surgery during the first 2 years of follow-up. Overall, visual acuity increased by 23 letters from the preoperative visit to the 3-month visit (95% confidence interval [CI], 17-29 letters; P < 0.001) and was stable through 9 months of follow-up. Eyes presumed to have a more severe cataract, as measured by inability to grade vitreous haze, gained an additional 42 letters (95% CI, 34-56 letters; P < 0.001) beyond the 13-letter gain in eyes that had gradable vitreous haze before surgery (95% CI, 9-18 letters; P < 0.001) 3 months after surgery, making up for an initial difference of -45 letters at the preoperative visit (95% CI, -56 to -34 letters; P < 0.001). Black race, longer time from uveitis onset, and hypotony were associated with worse preoperative visual acuity (P < 0.05), but did not affect postsurgical recovery (P > 0.05, test of interaction). After adjusting for other risk factors, there was no significant difference in the improvement in visual acuity between the 2 treatment groups (implant vs. systemic therapy, 2 letters; 95% CI, -10 to 15 letters; P = 0.70). Cataract surgery resulted in substantial

  16. BJ-3105, a 6-Alkoxypyridin-3-ol Analog, Impairs T Cell Differentiation and Prevents Experimental Autoimmune Encephalomyelitis Disease Progression

    PubMed Central

    Timilshina, Maheshwor; Kang, Youra; Dahal, Ishmit; You, Zhiwei; Nam, Tae-gyu; Kim, Keuk-Jun

    2017-01-01

    CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement. BJ-3105 ameliorated the experimental autoimmune encephalomyelitis (EAE) model by reducing Th1 and Th17 generation. Notably, Th cell differentiation was significantly suppressed by BJ-3105 treatment without inhibiting in vitro proliferation of T cells or inducing programmed cell death. Mechanistically, BJ-3105 inhibited the phosphorylation of JAK and its downstream signal transducer and activator of transcription (STAT) that is critical for Th differentiation. These results demonstrated that BJ-3105 inhibits the phosphorylation of STAT in response to cytokine signals and subsequently suppressed the differentiation of Th cell responses. PMID:28095433

  17. Structural changes of the choroid in sarcoid- and tuberculosis-related granulomatous uveitis

    PubMed Central

    Mehta, H; Sim, D A; Keane, P A; Zarranz-Ventura, J; Gallagher, K; Egan, C A; Westcott, M; Lee, R W J; Tufail, A; Pavesio, C E

    2015-01-01

    Aim The aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT). Methods Twenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software. Results The main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller's large vessel and Sattler's medium vessel layers) at the macula region. The ratio of Haller's large vessel to Sattler's medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72 μm)) compared with sarcoid uveitis (1.07 (=137.70/128.69 μm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1 μm (interquartile range (IQR)=147.0–253.4 μm) compared with those with VA <0.3 LogMAR (292.4 μm (IQR=240.1–347.6 μm)) at the total macula circle (P=0.004). At the foveal central subfield, the median choroidal thickness was 336.8 μm (IQR=272.3–375.4 μm) in active compared with 239.3 μm (IQR=195.3–330.9 μm) in quiescent disease (P=0.04). Conclusion A disproportionately enlarged Sattler's layer may indicate a diagnosis of sarcoid-related uveitis, and choroidal thickening may be a feature of active granulomatous uveitis. PMID:26021867

  18. An acidic polysaccharide of Panax ginseng ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells.

    PubMed

    Hwang, Insun; Ahn, Ginnae; Park, Eunjin; Ha, Danbee; Song, Jie-Young; Jee, Youngheun

    2011-08-30

    An acidic polysaccharide of Panax ginseng (APG), so called ginsan, is a purified polysaccharide. APG has multiple immunomodulatory effects of stimulating natural killer (NK) and T cells and producing a variety of cytokines that proved to diminish the proinflammatory response, and protect from septic lethality. To determine APG's role in the autoimmune demyelinating disease, we tested whether APG can regulate inflammatory and encephalitogenic response in experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). Here, we demonstrate the therapeutic efficacy of the APG which induces the suppression of an encephalitogenic response during EAE. APG significantly ameliorates the progression of EAE by inhibiting the proliferation of autoreactive T cells and the production of inflammatory cytokines such as IFN-γ, IL-1β and IL-17. More importantly, APG promotes the generation of immunosuppressive regulatory T cells (Tregs) through the activation of transcription factor, Foxp3. Furthermore, the depletion of CD25+ cells from APG-treated EAE mice abrogates the beneficial effects of EAE. The capacity of APG to induce clinically beneficial effects furthers our understanding of the basis for its therapeutic immunosuppression of EAE and, possibly, MS. Thus, our results suggest that APG may serve as an effective therapy for MS and other autoimmune diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Diagnosis of Lyme-associated uveitis: value of serological testing in a tertiary centre.

    PubMed

    Bernard, Alexia; Kodjikian, Laurent; Abukhashabh, Amro; Roure-Sobas, Chantal; Boibieux, Andre; Denis, Philippe; Broussolle, Christiane; Seve, Pascal

    2018-03-01

    To determine the frequency and clinical presentation of Lyme disease in patients with uveitis and to assess the value of Borrelia burgdorferi serological testing. Retrospective study on all patients with uveitis who were referred to our tertiary hospital were serologically tested for Lyme in our laboratory between 2003 and 2016. Screening consisted of determining B. burgdorferi serum IgG and IgM by ELISA method. The patient's serology was considered as positive if the ELISA-positive result in IgM and/or IgG was confirmed by an immunoblot positive in IgM and/or IgG. Lyme-associated uveitis was diagnosed based on serological results as well as response to antibiotics and exclusion of other diagnosis. Of the 430 patients with uveitis (60% women, mean age 49 years) fulfilling inclusion criteria, 63 (14.7%) had an ELISA-positive serology, confirmed by immunoblot for 34 patients (7.9%). The diagnosis of Lyme-associated uveitis was finally retained in seven patients (1.6%). These patients reported either a previous exposure including tick bite or forest walks (n=5), symptoms suggestive of Lyme disease (n=5) and resistance to local and/or systemic steroids (n=7). Among the remaining 27 positive patients, 22 had other established aetiologies and 5 other were unclassified. The seroprevalence of B. burgdorferi among our patients with uveitis was 7.9% compared with 6 to 8.5% in the general French population which leads to a low predictive value of serological testing. Its use should be reserved for patients with unexplained uveitis, an exposure history, systemic findings suggestive of Lyme disease and steroids resistance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. High prevalence of fastidious bacteria in 1520 cases of uveitis of unknown etiology.

    PubMed

    Drancourt, Michel; Berger, Pierre; Terrada, Céline; Bodaghi, Bahram; Conrath, John; Raoult, Didier; LeHoang, Phuc

    2008-05-01

    The etiologic evaluation of uveitis is frequently unsuccessful when noninvasive methods are used. We conducted a prospective study to evaluate systematic screening for pathogens of uveitis. All patients with uveitis referred to the participating tertiary ophthalmology departments from January 2001 to September 2007 underwent intraocular and serum specimen collection. The standardized protocol for laboratory investigations included universal polymerase chain reaction (PCR)-based detection of any bacteria and mycoses, specific PCR-based detection of fastidious (difficult-to-grow) bacteria and herpes viruses, and culture of vitreous fluid. Sera were tested for fastidious bacteria. Among the 1321 included patients (1520 specimens), infection was diagnosed in 147 (11.1%) patients: 78 (53%) were caused by fastidious bacteria that included spirochetes, Bartonella species, intracellular bacteria (Chlamydia species, Rickettsia species, Coxiella burnetii), and Tropheryma whipplei; 18 by herpes viruses; and 9 by fungi. Bartonella quintana, Coxiella burnetii, Paracoccus yeei, Aspergillus oryzae, and Cryptococcus albidus were found to be associated with uveitis for the first time, to our knowledge. We recommend applying a 1-step diagnostic procedure that incorporates intraocular, specific microbial PCR with serum analyses in tertiary centers to determine the etiology of uveitis.

  1. From microbiome to infectome in autoimmunity.

    PubMed

    Bogdanos, Dimitrios P; Sakkas, Lazaros I

    2017-07-01

    The current review discusses the pros and cons of the microbiome studies conducted in search of the association between microbiota and autoimmunity. We focus on the role of infectome and autoinfectome as a bridge to link the findings of microbiome studies with those emerging from investigations of the role of specific viruses and antiviral responses as triggers of autoimmunity (through various mechanisms such as molecular mimicry). The 'usual suspects', such as herpetoviruses and Escherichia coli, are thoroughly discussed in light of the data emerged by the microbiome studies, using as examples specific autoimmune rheumatic diseases and inflammatory bowel diseases. We conclude that the studies of the oral cavity, gastrointestinal, and urinary tract microbiome are informative but can only be useful if further explored from the infectome perspective. This means that the plethora of bacteria associated with autoimmune diseases from microbiome studies can be and must be tested experimentally. If certain bacteria are associated directly or indirectly with autoimmune diseases, specific immunological mechanisms must be identified.

  2. Randomized Controlled Trial Evaluating a Standardized Strategy for Uveitis Etiologic Diagnosis (ULISSE).

    PubMed

    de Parisot, Audrey; Kodjikian, Laurent; Errera, Marie-Hélène; Sedira, Neila; Heron, Emmanuel; Pérard, Laurent; Cornut, Pierre-Loïc; Schneider, Christelle; Rivière, Sophie; Ollé, Priscille; Pugnet, Grégory; Cathébras, Pascal; Manoli, Pierre; Bodaghi, Bahram; Saadoun, David; Baillif, Stéphanie; Tieulie, Nathalie; Andre, Marc; Chiambaretta, Frédéric; Bonin, Nicolas; Bielefeld, Philip; Bron, Alain; Mouriaux, Frédéric; Bienvenu, Boris; Vicente, Stéphanie; Bin, Sylvie; Broussolle, Christiane; Decullier, Evelyne; Sève, Pascal

    2017-06-01

    To prospectively assess the efficiency of a standardized diagnostic approach, compared to an open strategy, for the etiologic diagnosis of uveitis. Noninferiority, prospective, multicenter, clustered randomized controlled trial. Consecutive patients with uveitis, who visited 1 of the participating departments of ophthalmology, were included. In the standardized group, all patients had a minimal evaluation regardless of the type of uveitis (complete blood count, erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test, syphilis serology, and chest radiograph) followed by more complex investigations according to ophthalmologic findings. In the open group, the ophthalmologist could order any type of investigation. Main outcome was the percentage of etiologic diagnoses at 6 months. Nine hundred and three patients with uveitis were included from January 2010 to May 2013 and the per-protocol population comprised 676 patients (open 373; standardized 303). Mean age at diagnosis was 46 years. Anatomic distribution of uveitis was as follows: anterior (60.8% and 72.3%, P = .0017), intermediate (11.7% and 12.3%, P = .8028), posterior (17.8% and 8.2%, P = .0004), and panuveitis (15.3% and 15.2%, P = .9596). An etiologic diagnosis was established in 54.4% of cases in the open group and 49.5% in the standardized group (P = .2029). The difference between both strategies (standardized minus open) was -4.9% (95% CI [-12.5%; 2.6%]). There were more investigations in the open group than in the standardized group (5371 vs 3759, P < .0001). The standardized strategy appears to be an efficient diagnostic approach for the etiologic diagnosis of uveitis, although its noninferiority cannot be proved. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Clinical features of paediatric uveitis at a tertiary referral centre in São Paulo, SP, Brazil.

    PubMed

    Souto, Fernanda Maria Silveira; Giampietro, Bárbara Vilela; Takiuti, Julia Thiemi; Campos, Lucia Maria Arruda; Hirata, Carlos Eduardo; Yamamoto, Joyce Hisae

    2018-06-15

    To analyse the clinical features, systemic associations, treatment and visual outcomes of uveitis in children from a referral centre in São Paulo, Brazil. Clinical records of patients under 16 years old who attended the Uveitis Service, Hospital das Clinicas, Faculdadede Medicina, Universidade de São PauloFMUSP, between April and September 2017, were reviewed retrospectively. Patients with incomplete medical records, previous ocular trauma, or less than six6 months of follow-up were excluded. Thirty-nine children (25 female/14 male) were included. There was predominance of bilateral (89.7%), asymptomatic (56.4%) and recurrent/chronic cases (84.6%). The mean age at study inclusion was 10.7±3.4 years (range 3-16 years). Improvement or preservation of visual acuity (VA) was observed in 27 patients (84%); VA was not informed in 8 patients. Patients were referred early to tertiary centre (55% within 6 months of uveitis diagnosis). Anterior uveitis was the most common involvement (46%), followed by intermediate uveitis (26%). Juvenile idiopathic arthritis (JIA)-associated uveitis (41%) and immune-mediated intermediate uveitis (25.6%) were the principal non-infectious conditions; ocular toxoplasmosis (7.7%) and toxocariasis (5.1%) were the most common infectious conditions. Ocular complications were observed at first visit in 46% of patients and in 90% during final evaluation. Oral prednisone, immunosuppressive therapy (IMT) and/or biologic agents were used in all non-infectious conditions (32 children, 82%); IMT and/or biologic agents were used in all patients with JIA-associated uveitis and in 50% of patients with immune-mediated intermediate uveitis. Paediatric patients with uveitis are referred early to this centre and, although severe, adequate management with systemic IMT may preserve VA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless

  4. Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

    PubMed

    Garcia-Geremias, M; Carreño, E; Epps, S J; Lee, R W J; Dick, A D

    2015-04-01

    Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

  5. Diagnostic yield of heat shock protein 70 (HSP-70) and anti-HSP-70 in Behcet-induced uveitis.

    PubMed

    Sahebari, M; Hashemzadeh, K; Mahmoudi, M; Saremi, Z; Mirfeizi, Z

    2013-06-01

    Heat shock proteins (HSPs) are intracellular proteins with pro- and anti-inflammatory actions, playing an important role in the pathogenesis of Behcet's disease (BD). Diagnosis of BD uveitis in early stages is still problematic, thus this study was undertaken to determine diagnostic values of serum HSP- and anti-HSP-70 in BD uveitis. Serum levels of HSP- and anti-HSP-70 were measured in 53 patients with BD (26 with and 27 without uveitis). In control group, 25 age- and sex-matched idiopathic uveitis patients were enrolled consecutively. Both groups had no medical problems save uveitis at the time of sampling. Confounders like medications were analysed subsequently. HSP- and anti-HSP-70 values were measured by commercial ELISA kits. Data were analysed by spss 11.5 and medcalc 11.5.1 software. The Mean HSP-70 serum levels were different among aforementioned subgroups (P = 0.001, anova). They were elevated in BD uveitis compared with BD without uveitis (4.84 ± 4.21 versus 2.24 ± 2.08 ng/ml; P = 0.045). HSP-70 in sera of BD uveitis was also higher than that parameter in patients with idiopathic uveitis (4.84 ± 4.21 versus 2.37 ± 3.30 ng/ml; P = 0.001; cut-off point value 1.0 9 ng/ml, 95% CI 0.61-0.86, P = 0.0002, ß = 0.06). However, there was not any statistical difference among those groups in the serum anti-HSP-70 levels (P = 0.63, anova). Multiple regression analysis demonstrated that among different confounders, only prednisolone increases and BD uveitis decreases HSP-70 levels independently. This prospective cross-sectional study suggested that HSP-70 serum level is impressed over the course of BD uveitis, and it could be utilized to diagnose or predict developing it. © 2013 The Authors. Scandinavian Journal of Immunology © 2013 Blackwell Publishing Ltd.

  6. Pentoxifylline attenuates cytokine stress and Fas system in syngeneic liver proteins induced experimental autoimmune hepatitis.

    PubMed

    Hendawy, Nevien

    2017-08-01

    Apoptosis is a hallmark in the pathogenesis of autoimmune hepatitis (AIH). Cytokine stresses and extrinsic apoptotic pathway have been implicated in this type of hepatic injury. Pentoxifylline plays an important role in controlling inflammation and apoptosis in different autoimmune diseases. To assess the protective effect of pentoxifylline for 30days against pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) and mediators of extrinsic apoptotic pathway involving TNF receptor 1 (TNFR1) and its ligand TNF-α and Fas receptor and its ligand (FasL) in experimental autoimmune hepatitis (EAH) model. EAH was induced by intraperitoneal injection of syngeneic liver antigen emulsified in complete Freund's adjuvant (CFA) in male C57BL/6 mice. Five groups of mice were used: two control groups; Control PBS group and Control CFA group, EAH group and two EAH+pentoxifylline treated groups in doses (100 or 200mg/kg/d, given by oral gavage). Serum transaminase, pro-inflammatory cytokines (TNF-α and interferon-γ) and hepatic caspase-8 and 3 activities were evaluated. Signs of autoimmune hepatitis were confirmed by liver histology. In addition, hepatic TNFR1, Fas and FasL mRNA expression were assayed. Serum transaminase levels and signs of AIH observed in EAH mice were significantly reduced by pentoxifylline. Upregulated serum TNF-α, IFN-γ, hepatic caspase-8 and 3 activities and TNFR1, Fas and FasL mRNA expression in liver tissues in EAH group were significantly downregulated by pentoxifylline. Pentoxifylline protects against syngeneic liver antigen induced hepatitis and associating apoptosis through attenuating the exaggerated cytokine release and extrinsic apoptotic pathway. Thus, this may represent a new therapeutic strategy for hepatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Recurrent uveitis and pigment dispersion in an eye with in-the-bag acrylic foldable intraocular lens.

    PubMed

    Thakur, Monica; Bhatia, Prashant; Chandrasekhar, Garudadri; Senthil, Sirisha

    2016-02-26

    Phacoemulsification with in-the-bag intraocular lens (IOL) implantation is the standard procedure for cataract surgery. Pigment dispersion and uveitis can result when an IOL is placed in the sulcus. We report a case of a 64-year-old woman, with pigmentary glaucoma, who developed recurrent uveitis following uneventful cataract surgery and an in-the-bag hydrophobic acrylic IOL implant. Recurrent uveitis did not subside despite use of topical steroids over 3 months. Dilated examination revealed capsulophimosis with anterior dislocation of the IOL haptic. The mechanical trauma to the iris due to the displaced haptic was implicated as the cause of recurrent uveitis, which completely resolved after capsular excision and IOL repositioning. This case illustrates a rare cause of recurrent uveitis due to IOL haptic dislocation following severe capsulophimosis. 2016 BMJ Publishing Group Ltd.

  8. [Macular Edema in Uveitis - Steroids or VEGF Inhibitors?

    PubMed

    Heinz, Carsten; Heiligenhaus, Arnd

    2017-06-09

    Macular edema in uveitis patients is certainly the most frequent complication leading to a permanent and irreversible reduction in vision during the course of the disease. Thanks to optical coherence tomography (OCT) technology and fluorescein angiography (FAG), significantly more macular edemas are detected. Macular edema can be found in various uveitis varieties and can show different clinical patterns. All macular edema should be treated. Macular edema with active inflammation usually reacts very well to general uveitis treatment. In the case of eyes without visible inflammation, however, the response to such therapy is usually less effective. According to the latest treatment recommendations, dexamethasone implants should be used as the first intravitreal therapy. Vascular endothelial growth factor inhibitors (VEGF inhibitors) are second-line treatment regimens. The choice of therapy is, therefore, primarily based on the degree of inflammation and the individual complications, such as glaucoma, lens situation or previous increase in IOP after steroid administration. These individual complications may allow using VEGF inhibitors as first line treatment. An improvement in the macular edema can be achieved with both groups of active substances. Georg Thieme Verlag KG Stuttgart · New York.

  9. Serum and vitreous humor antibody titers in and isolation of Leptospira interrogans from horses with recurrent uveitis.

    PubMed

    Wollanke, B; Rohrbach, B W; Gerhards, H

    2001-09-15

    To measure antibody titers against Leptospira interrogans in serum and vitreous humor and determine the prevalence of L interrogans in vitreous humor of horses with recurrent uveitis. Cross-sectional study. 242 horses (270 eyes) with recurrent uveitis undergoing vitrectomy and 39 control horses (54 eyes) without any history or clinical signs of recurrent uveitis undergoing euthanasia or enucleation for unrelated reasons. Serum and vitreous humor were tested for antibodies against 13 serovars of L interrogans. Vitreous humor was submitted for leptospiral culture; isolates were typed to the serogroup level. Leptospira interrogans was isolated from vitreous humor from 120/229 (52%) horses (126/252 [50%] eyes) with recurrent uveitis but was not isolated from vitreous humor from 36 eyes of 21 control horses. Duration of recurrent uveitis was > or = 1 year for 45 of the 120 (38%) horses from which the organism was isolated. Geometric mean antibody titers against L interrogans in the vitreous humor and serum of horses with recurrent uveitis were 1:1,332 and 1:186, respectively. Only 91 of 120 (76%) horses from which the organism was isolated had a 4-fold or greater difference between serum and vitreous humor antibody titers. Results suggest that persistent ocular infection with L interrogans is common in horses with recurrent uveitis. A 4-fold increase in vitreous humor versus serum antibody titers may not be a sensitive test for the diagnosis of L interrogans-induced recurrent uveitis. We hypothesize that the immune component of recurrent uveitis can be directly induced and maintained by persistent infection of the eye with L interrogans.

  10. Helicobacter pylori and autoimmune disease: Cause or bystander

    PubMed Central

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  11. Uveitis in São Paulo, Brazil: 1053 New Patients in 15 Months.

    PubMed

    Gonzalez Fernandez, Delia; Nascimento, Heloisa; Nascimento, Caio; Muccioli, Cristina; Belfort, Rubens

    2017-06-01

    To describe the clinical profile of uveitis and analyze changes over a 34-year period in the frequency of different entities and demographics, anatomic data, diagnoses, and systemic associations in São Paulo, Brazil. A total of 1053 consecutive patients who presented for the first time at the outpatient uveitis clinic were analyzed in a prospective, observational study, conducted between July 2012 and September 2013. Age, gender, clinical characteristics, visual acuity, and clinical and etiologic diagnoses in patients with and without human immunodeficiency virus (HIV) were studied. Mean age was 39.8 ± 17.8 years (56.8% female), with most between 41 and 64 years (41.79%); 10.9% of the patients were HIV-positive and 8.1% were legally blind (best-corrected visual acuity (BCVA): ≤ 20/400) at the first evaluation. The posterior, bilateral, and chronic forms of uveitis occurred most frequently and toxoplasmosis was the main cause (24.03%) but was less frequent than in 1980; the same was true for Fuchs heterochromic iridocyclitis. Syphilis, tuberculosis, Vogt-Koyanagi-Harada disease, and juvenile idiopathic arthritis-related uveitis had increased incidence rates. The current results can help determine the present epidemiology of uveitis and its changes over time in Brazil and increases essential information about the disease. Many uveitic entities are curable and visual damage can be prevented or limited if treated early and appropriately.

  12. [Sarcoidosis and uveitis : An update].

    PubMed

    Garweg, J G

    2017-06-01

    Ocular involvement in sarcoidosis is present in up to one third of patients and is frequently manifested before the underlying systemic disease has been diagnosed. With a view to the therapeutic consequences an early diagnosis of the underlying disease is advantageous. In cases of visual loss early diagnostic measures include invasive procedures, such as ultrasound-guided bronchoalveolar lavage and transbronchial biopsy, if nodular conjunctival or cutaneous manifestations which would confirm the diagnosis are not present. Sufficiently sensitive biomarkers of disease activity have not yet been identified. As elevated activity of angiotensin-converting enzyme (ACE) and lysozyme are associated with disease activity they may be supportive of but not specific for the diagnosis. Other indicators include calcemia, calciuria, augmented activity of hepatic enzymes, cutaneous anergy and hilar changes in the lungs. In patients with newly diagnosed anterior uveitis presenting with granulomatous mutton-fat corneal precipitates, snow balls and vitreous body base condensates with mild retinal periphlebitis in intermediate uveitis as well as multifocal choroiditis (creamy choroidal lesions at different stages of activity and approximately 500 µm in diameter), a diagnosis of sarcoidosis has to be considered and tuberculosis should be excluded, even in the absence of a known systemic disease. Anterior uveitis is frequently a self-limiting condition, which can be well-controlled with topical steroids. On the other hand, intermediate, posterior and panuveitis are typically associated with a chronic course and require systemic therapy to prevent severe loss of vision. If the response to systemic corticosteroids is insufficient, treatment with immunomodulatory agents and biologics is initiated at progressively earlier stages, with a view to averting permanent organ damage and frequently with a positive impact on the short and long-term outcomes, even in therapy-refractive cases.

  13. Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

    PubMed Central

    Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

    2014-01-01

    Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

  14. Iris autofluorescence in Fuchs' heterochromic uveitis.

    PubMed

    Liu, Qian; Jia, Yading; Zhang, Suhua; Xie, Juan; Chang, Xin; Hou, Jia; Li, Gaiyun; Koch, Douglas D; Wang, Li

    2016-10-01

    To explore the characteristic autofluorescence patterns of iris depigmentation in eyes diagnosed with Fuchs' heterochromic uveitis (FHU). Near-infrared autofluorescence images and colour images of iris were taken in 21 eyes of 21 patients with FHU, 30 eyes of 15 normal subjects, 30 eyes of 15 normal age-related iris atrophy and 33 eyes of 20 patients with uveitis other than FHU. The confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2, HRA2) was used for melanin-related autofluorescence imaging. The indocyanine green angiography mode of HRA2 was applied for near-infrared laser imaging, and the wavelength of the excitation laser was 795 nm. Iris colour images were also taken with the slit lamp. In normal iris, moderately intense autofluorescence was noted for the pigment ruff at the pupillary border, the crests in the pupillary zone and the collarette; and there was mild autofluorescence in the ciliary zone. In eyes with age-related iris atrophy and uveitis, much less autofluorescence was seen than the healthy normal irides. In eyes with FHU, there was moderate but discontinuous autofluorescence in the pigment ruff, a petaloid pattern of autofluorescence in the pupillary zone, moderate autofluorescence in the collarette and reticular pattern of autofluorescence in the ciliary zone. Characteristic autofluorescence patterns appeared in eyes diagnosed with FHU. Near-infrared autofluorescence is a promising objective technique to document the iris changes in FHU. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease.

    PubMed

    Chancellor, John R; Padmanabhan, Sriranjani P; Greenough, Thomas C; Sacra, Richard; Ellison, Richard T; Madoff, Lawrence C; Droms, Rebecca J; Hinkle, David M; Asdourian, George K; Finberg, Robert W; Stroher, Ute; Uyeki, Timothy M; Cerón, Olga M

    2016-02-01

    We report a case of probable Zaire Ebola virus-related ophthalmologic complications in a physician from the United States who contracted Ebola virus disease in Liberia. Uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. This case highlights immune phenomena that could complicate management of Ebola virus disease-related uveitis during convalescence.

  16. Chronic Refractory Uveitis in a Patient with Childhood-Onset Cyclic Neutropenia

    PubMed Central

    Chen, Li-Li; Toyoguchi, Mitsuko; Shimakawa, Machiko; Hori, Sadao

    2011-01-01

    We report a rare case of chronic refractory uveitis in a patient with childhood-onset cyclic neutropenia (CN). A 19-year-old woman, who had a history of CN beginning at age 2, presented with bilateral chronic nongranulomatous uveitis, complicated cataract, retinal vasculitis, cystoids macular edema, and vitreous hemorrhage. She had recurrent episodes of oral ulcers, tonsillitis, genital ulcers, and folliculitis during neutropenic nadir. After the resumption of granulocyte colony-stimulating factor therapy for her CN, vitreous hemorrhage in both eyes followed. Her eyes were treated with topical corticosteroids, retinal photocoagulation, and cataract surgery. Blood and bone marrow test results confirmed the diagnosis of CN. She also fulfilled the diagnostic criteria of Behçet's disease, though clinical features of her uveitis were dissimilar to those found in that disease. PMID:21677883

  17. A Herpes Simplex Virus-Derived Replicative Vector Expressing LIF Limits Experimental Demyelinating Disease and Modulates Autoimmunity

    PubMed Central

    Nygårdas, Michaela; Paavilainen, Henrik; Müther, Nadine; Nagel, Claus-Henning; Röyttä, Matias; Sodeik, Beate; Hukkanen, Veijo

    2013-01-01

    Herpes simplex virus type 1 (HSV-1) has properties that can be exploited for the development of gene therapy vectors. The neurotropism of HSV enables delivery of therapeutic genes to the nervous system. Using a bacterial artificial chromosome (BAC), we constructed an HSV-1(17+)-based replicative vector deleted of the neurovirulence gene γ134.5, and expressing leukemia inhibitory factor (LIF) as a transgene for treatment of experimental autoimmune encephalomyelitis (EAE). EAE is an inducible T-cell mediated autoimmune disease of the central nervous system (CNS) and is used as an animal model for multiple sclerosis. Demyelination and inflammation are hallmarks of both diseases. LIF is a cytokine that has the potential to limit demyelination and oligodendrocyte loss in CNS autoimmune diseases and to affect the T-cell mediated autoimmune response. In this study SJL/J mice, induced for EAE, were treated with a HSV-LIF vector intracranially and the subsequent changes in disease parameters and immune responses during the acute disease were investigated. Replicating HSV-LIF and its DNA were detected in the CNS during the acute infection, and the vector spread to the spinal cord but was non-virulent. The HSV-LIF significantly ameliorated the EAE and contributed to a higher number of oligodendrocytes in the brains when compared to untreated mice. The HSV-LIF therapy also induced favorable changes in the expression of immunoregulatory cytokines and T-cell population markers in the CNS during the acute disease. These data suggest that BAC-derived HSV vectors are suitable for gene therapy of CNS disease and can be used to test the therapeutic potential of immunomodulatory factors for treatment of EAE. PMID:23700462

  18. Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis.

    PubMed

    Hasanreisoglu, Murat; Cubuk, Mehmet Ozgur; Ozdek, Sengul; Gurelik, Gokhan; Aktas, Zeynep; Hasanreisoglu, Berati

    2017-02-01

    To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment. In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group. The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (p<0.05). When the two groups were compared after administration of IFNα2a therapy, no statistical difference was found in terms of uveitis attack/year and attack-free intervals, with a partial response to both treatments. IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

  19. Characterization of rat model of acute anterior uveitis using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

    2015-03-01

    Uveitis, or ocular inflammation, is a cause of severe visual impairment. Rodent models of uveitis are powerful tools used to investigate the pathological mechanisms of ocular inflammation and to study the efficacy of new therapies prior to human testing. In this paper, we report the utility of spectral-domain optical coherence tomography (SD-OCT) angiography in characterizing the inflammatory changes induced in the anterior segment of a rat model of uveitis. Acute anterior uveitis (AAU) was induced in two rats by intravitreal injection of a killed mycobacterial extract. One of them received a concurrent periocular injection of steroids to model a treatment effect. OCT imaging was performed prior to inflammation induction on day 0 (baseline), and 2 days post-injection (peak inflammation). Baseline and inflamed images were compared. OCT angiography identified swelling of the cornea, inflammatory cells in the anterior and posterior chambers, a fibrinous papillary membrane, and dilation of iris vessels in the inflamed eyes when compared to baseline images. Steroid treatment was shown to prevent the changes associated with inflammation. This is a novel application of anterior OCT imaging in animal models of uveitis, and provides a high resolution, in vivo assay for detecting and quantifying ocular inflammation and the response to new therapies.

  20. Immunopharmacotherapy of non-infectious uveitis: where do we stand?

    PubMed

    Agrawal, Rupesh; Lee, Cecilia; Phatak, Sumita; Pavesio, Carlos

    2014-12-01

    With ever-evolving concept of personalised medicine backed up with specific biomarkers for ocular inflammatory disease, there is a sudden surge of using biologics in non-infectious recalcitrant posterior uveitis. Have we understood these biologic agents enough to embark on this long enduring journey with the patient to optimise control of intraocular inflammation? On the other hand, there is still a strong inhibition of using these novel agents in management of uveitis even at tertiary referral centres. Immunopharmacotherapy of non-infectious uveitis poses a significant conundrum for both physicians and patients as it is like a two-edged sword effective to control inflammation but at the same time potentially toxic, suspected of causing long-term adverse effects. Systemic immunosuppressive therapy is used in a substantial number of most vision-threatening ocular inflammatory diseases. There is lack of randomised control trials establishing the safety of this therapy and our current practice pattern is based on retrospective studies and personal experience in using this treatment modality. This overview will highlight on the current dilemma faced by the clinicians in opting for steroid-sparing immunosuppressive therapy.

  1. Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis.

    PubMed

    Gilger, B C; Wilkie, D A; Davidson, M G; Allen, J B

    2001-12-01

    To evaluate the use of an intravitreal sustained-release cyclosporine (CsA) delivery device for treatment of horses with naturally occurring recurrent uveitis. 16 horses with recurrent uveitis. Horses with frequent recurrent episodes of uveitis or with disease that was progressing despite appropriate medication were selected for this study. Additional inclusion criteria included adequate retinal function as determined by use of electroretinography, lack of severe cataract formation, and no vision-threatening ocular complications (eg, retinal detachment, severe retinal degeneration, and posterior synechia). Sustained-release CsA delivery devices (4 microg of CsA/d) were implanted into the vitreous through a sclerotomy at the pars plana. Reexaminations were performed 1, 3, 6, and 12 months after implantation, then continued annually. Ophthalmic changes, number of recurrent episodes of uveitis, and vision were recorded. The rate of recurrent episodes after device implantation (0.36 episodes/y) was less than prior to surgery (75 episodes/y). In addition, only 3 horses developed episodes of recurrent uveitis after surgery. Vision was detected in 14 of 16 affected eyes at a mean follow-up time of 13.8 months (range, 6 to 24 months). This intravitreal sustained-release CsA delivery device may be a safe and important tool for long-term treatment of horses with chronic recurrent uveitis.

  2. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    PubMed

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  3. Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, or Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment Trial and Follow-up Study.

    PubMed

    2015-10-01

    To evaluate the risks and quality-of-life (QoL) outcomes of fluocinolone acetonide implant versus systemic therapy with corticosteroid and immunosuppression when indicated for intermediate uveitis, posterior uveitis, and panuveitis. Additional follow-up of a randomized trial cohort. Two hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis, randomized to implant or systemic therapy. Randomized subjects with intermediate uveitis, posterior uveitis, or panuveitis (479 eyes) were followed up over 54 months, with 79.2% completing the 54-month visit. Local and systemic potential complications of the therapies and self-reported health utility and vision-related and generic health-related QoL were studied prospectively. Among initially phakic eyes, cataract and cataract surgery occurred significantly more often in the implant group (hazard ratio [HR], 3.0; P = 0.0001; and HR, 3.8; P < 0.0001, respectively). In the implant group, most cataract surgery occurred within the first 2 years. Intraocular pressure elevation measures occurred more frequently in the implant group (HR range, 3.7-5.6; all P < 0.0001), and glaucoma (assessed annually) also occurred more frequently (26.3% vs. 10.2% by 48 months; HR, 3.0; P = 0.0002). In contrast, potential complications of systemic therapy, including measures of hypertension, hyperlipidemia, diabetes, bone disease, and hematologic and serum chemistry indicators of immunosuppression toxicity, did not differ between groups through 54 months. Indices of QoL initially favored implant therapy by a modest margin. However, all summary measures of health utility and vision-related or generic health-related QoL were minimally and nonsignificantly different by 54 months, with the exception of the 36-item Short-Form Health Survey physical component summary score, which favored implant by a small margin at 54 months (3.17 on a scale of 100; P = 0.01, not adjusted for multiple comparisons). Mean QoL results were

  4. Optic nerve and retinal features in uveitis associated with juvenile systemic granulomatous disease (Blau syndrome).

    PubMed

    Carreño, Ester; Guly, Catherine M; Chilov, Michael; Hinchcliffe, Annie; Arostegui, Juan I; Lee, Richard W J; Dick, Andrew D; Ramanan, Athimalaipet V

    2015-05-01

    To determine whether patients with juvenile systemic granulomatous disease (JSGD) (Blau syndrome) and uveitis have a characteristic ocular phenotype. Clinical and imaging data were collected retrospectively from patients attending the Regional Combined Paediatric Rheumatology and Ocular Inflammatory Service, Bristol Eye Hospital. General demographic information, laterality of the uveitis, age at onset, anatomical classification and course of the uveitis, clinical phenotype and specific NOD2 mutation were recorded for each patient. Seventeen eyes from nine patients (five males; four females) were included in the study. Mean age at the disease onset was 15 months, range 1-84 months. Eight patients had bilateral uveitis. Anterior uveitis was present in five eyes, intermediate uveitis in two eyes, and there were 10 eyes with panuveitis, manifesting as multifocal choroiditis. Appearance of optic disc included indistinct disc margins in six eyes, optic nerve head pallor in six eyes, optic disc vessel sheathing in four eyes, and there was peripapillary hypo/hyperpigmentation in 13 eyes accompanied with characteristic peripapillary nodular excrescences. Among NOD2 mutations, the p.R334W was the most commonly detected (n: four cases), and three patients carried novel variants, the p.E338D and p.D390V variants in one patient, and the p.H520Y and p.Q809K variants in two different patients. Chronic bilateral panuveitis and a nodular peripapillary appearance in childhood onset uveitis are characteristic features of JSGD, which support the need for an appropriate genetic NOD2 analysis. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice

    PubMed Central

    Schmitz, Katja; de Bruin, Natasja; Bishay, Philipp; Männich, Julia; Häussler, Annett; Altmann, Christine; Ferreirós, Nerea; Lötsch, Jörn; Ultsch, Alfred; Parnham, Michael J; Geisslinger, Gerd; Tegeder, Irmgard

    2014-01-01

    R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4+CD25+FoxP3+ regulatory T cells, CTLA4+ inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial. PMID:25269445

  6. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

    PubMed

    Samson, C M; Waheed, N; Baltatzis, S; Foster, C S

    2001-06-01

    To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. Retrospective noncomparative interventional case series. All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

  7. Lack of consensus in the diagnosis and treatment for ocular tuberculosis among uveitis specialists.

    PubMed

    Lou, Susan M; Larkin, Kelly L; Winthrop, Kevin; Rosenbaum, James T

    2015-02-01

    To assess the approach of specialists to ocular tuberculosis (TB). The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1-75%) or that a patient with a risk factor for TB had ocular TB (range 0-90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

  8. Uveitis-glaucoma-hyphema syndrome associated with recurrent vitreous hemorrhage.

    PubMed

    Alfaro-Juárez, A; Vital-Berral, C; Sánchez-Vicente, J L; Alfaro-Juárez, A; Muñoz-Morales, A

    2015-08-01

    A 61-year-old pseudophakic male with recurrent blurred vision episodes associated with uveitis, hyphema, glaucoma and vitreous hemorrhage. Iris transillumination defects and apposition of the optic and iris were found. The patient was diagnosed with Uveitis-Glaucoma-Hyphema (UGH) Syndrome. Mechanical irritation of the iris is a consequence of intraocular lens malposition and causes UGH Syndrome. Occasionally it is associated with vitreous hemorrhage. Lens malposition is detected by optical coherence tomography and/or ultrasound biomicroscopy. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Helminth-induced Ly6Chi monocyte-derived alternatively activated macrophages suppress experimental autoimmune encephalomyelitis

    PubMed Central

    Terrazas, Cesar; de Dios Ruiz-Rosado, Juan; Amici, Stephanie A.; Jablonski, Kyle A.; Martinez-Saucedo, Diana; Webb, Lindsay M.; Cortado, Hanna; Robledo-Avila, Frank; Oghumu, Steve; Satoskar, Abhay R.; Rodriguez-Sosa, Miriam; Terrazas, Luis I.; Guerau-de-Arellano, Mireia; Partida-Sánchez, Santiago

    2017-01-01

    Helminths cause chronic infections and affect the immune response to unrelated inflammatory diseases. Although helminths have been used therapeutically to ameliorate inflammatory conditions, their anti-inflammatory properties are poorly understood. Alternatively activated macrophages (AAMϕs) have been suggested as the anti-inflammatory effector cells during helminth infections. Here, we define the origin of AAMϕs during infection with Taenia crassiceps, and their disease-modulating activity on the Experimental Autoimmune Encephalomyelitis (EAE). Our data show two distinct populations of AAMϕs, based on the expression of PD-L1 and PD-L2 molecules, resulting upon T. crassiceps infection. Adoptive transfer of Ly6C+ monocytes gave rise to PD-L1+/PD-L2+, but not PD-L1+/PD-L2− cells in T. crassiceps-infected mice, demonstrating that the PD-L1+/PD-L2+ subpopulation of AAMϕs originates from blood monocytes. Furthermore, adoptive transfer of PD-L1+/PD-L2+ AAMϕs into EAE induced mice reduced disease incidence, delayed disease onset, and diminished the clinical disability, indicating the critical role of these cells in the regulation of autoimmune disorders. PMID:28094319

  10. Autoimmunity and autoimmune co-morbidities in psoriasis.

    PubMed

    Furue, Kazuhisa; Ito, Takamichi; Tsuji, Gaku; Kadono, Takafumi; Nakahara, Takeshi; Furue, Masutaka

    2018-05-01

    Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the tumour necrosis factor-α/interleukin-23/interleukin-17 axis is now known to be the major mechanism in the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is co-morbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune co-morbidities in psoriasis. © 2018 John Wiley & Sons Ltd.

  11. Methotrexate: an option for preventing the recurrence of acute anterior uveitis.

    PubMed

    Muñoz-Fernández, S; García-Aparicio, A M; Hidalgo, M V; Platero, M; Schlincker, A; Bascones, M L; Pombo, M; Morente, P; Sanpedro, J; Martín-Mola, E

    2009-05-01

    To evaluate the efficacy of methotrexate (MTX) in preventing the recurrence of acute anterior uveitis (AAU). This prospective, open, longitudinal study included patients from June 2002 to March 2005 who had either three or more episodes of AAU in the previous year, or a recurrence of AAU within 3 months before starting the trial. We excluded uveitis of infectious origin, masquerade syndromes, and patients with contraindications to MTX. The response criteria were defined as an absence of symptoms and the presence of a normal ophthalmologic examination. The study outcome compared the number of flare-ups of uveitis over an MTX-treated for 1 year to the number of flare-ups of the same group during the previous year without MTX. A total of 571 patients with uveitis were evaluated during the period of the study, and 10 fulfilled the inclusion criteria. One patient refused the treatment, and nine completed the study. The mean number of recurrences in the pre-MTX year was 3.4 (SD: 0.52), which was significantly reduced to 0.89 (SD: 1.17) in the year of treatment (P=0.011). MTX treatment seems to reduce the number of flare-ups in patients with recurrent AAU.

  12. Effect and Mechanism of QiShenYiQi Pill on Experimental Autoimmune Myocarditis Rats.

    PubMed

    Lv, Shichao; Wu, Meifang; Li, Meng; Wang, Qiang; Xu, Ling; Wang, Xiaojing; Zhang, Junping

    2016-03-06

    To observe the effect of QiShenYiQi pill (QSYQ) on experimental autoimmune myocarditis rats, and to explore its mechanism of action. Lewis rats underwent the injection of myocardial myosin mixed with Freund's complete adjuvant were randomized into 3 groups: model, valsartan, and QSYQ groups. Rats injected with phosphate-buffered saline (PBS) mixed with Freund's complete adjuvant were used as the control group. Rats were euthanized at 4 and 8 weeks, and we weighed rat body mass, heart mass, and left ventricular mass. Myocardium sections were stained with hematoxylin and eosin (H&E) and Masson trichrome. Myocardial TGF-β1 and CTGF protein expression was detected by immunohistochemistry, and myocardial TGF-β1 and CTGF mRNA expression was detected by real-time qPCR. QSYQ reduced HMI and LVMI, as well as the histological score of hearts and CVF, which further decreased over time, and its effect was significantly greater than that of valsartan at 4 and 8 weeks. After 4 weeks, QSYQ inhibited the protein and mRNA expression of TGF-β1 and CTGF, and its effect on lowering CTGF was significantly greater than that of valsartan. In addition, after 8 weeks, QSYQ also inhibited the protein and mRNA expression of CTGF, whereas there was no significant difference in the expression of myocardial TGF-β1. This study provides evidence that QSYQ can improve cardiac remodeling of experimental autoimmune myocarditis rats. It also effectively improved the degree of myocardial fibrosis, which is related to the mechanism of regulation of TGF-β1 CTGF.

  13. Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in experimental autoimmune encephalomyelitis.

    PubMed

    Medina-Fernández, Francisco J; Luque, Evelio; Aguilar-Luque, Macarena; Agüera, Eduardo; Feijóo, Montserrat; García-Maceira, Fe I; Escribano, Begoña M; Pascual-Leone, Álvaro; Drucker-Colín, René; Túnez, Isaac

    2017-01-15

    Experimental autoimmune encephalomyelitis (EAE) is considered a valid experimental model for multiple sclerosis, a chronic neuroinflammatory condition of the central nervous system. Additionally, some evidence has shown that some microbial products such as the bacterial lipopolysaccharide could lead to the activation of reactive immune cells, triggering neuroinflammation. Several studies have found that transcranial magnetic stimulation (TMS) may exert a neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the neuroinflammation occurring in EAE. A total of 44 male Dark Agouti rats were used. EAE induction was performed administering subcutaneously at the dorsal base of the tail a single dose of myelin oligodendrocyte glycoprotein. Clinical evaluation of motor symptoms was performed. Brain and spinal cord were collected and analyzed for nitric oxide, bacterial lipopolysaccharide and lipopolysaccharide-binding protein. We also carried out a histologic exam, which included an astrocyte immunostaining and Nissl staining for the assessment of brain cell density and pyknotic nuclei. TMS effectively ameliorated motor impairment secondary to EAE. This form of magnetic field was capable of decreasing the proliferation of astrocytes as a response to the autoimmune attack, reducing the content of nitric oxide, bacterial lipopolysaccharide and lipopolysaccharide-binding protein in central nervous system. Moreover, in treated animals, brain cell density was improved and the number of pyknotic nuclei was decreased. Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in EAE. These results suggest that TMS could be a promising treatment for neuroinflammatory conditions such as multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Leptospiral uveitis - there is more to it than meets the eye!

    PubMed

    Verma, A; Stevenson, B

    2012-09-01

    Leptospirosis, caused by pathogenic species of genus Leptospira, is a highly prevalent zoonotic disease throughout many parts of the world, and an important emerging disease within the United States. Uveitis is a common complication of systemic infection in humans. A similar condition in horses is characterized by recurrent bouts of inflammation. In this article, we review advances in our understanding of leptospiral uveitis and its pathogenic mechanisms. © 2012 Blackwell Verlag GmbH.

  15. Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration.

    PubMed

    Rosenkranz, Eva; Maywald, Martina; Hilgers, Ralf-Dieter; Brieger, Anne; Clarner, Tim; Kipp, Markus; Plümäkers, Birgit; Meyer, Sören; Schwerdtle, Tanja; Rink, Lothar

    2016-03-01

    The essential trace element zinc is indispensable for proper immune function as zinc deficiency accompanies immune defects and dysregulations like allergies, autoimmunity and an increased presence of transplant rejection. This point to the importance of the physiological and dietary control of zinc levels for a functioning immune system. This study investigates the capacity of zinc to induce immune tolerance. The beneficial impact of physiological zinc supplementation of 6 μg/day (0.3mg/kg body weight) or 30 μg/day (1.5mg/kg body weight) on murine experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis with a Th1/Th17 (Th, T helper) cell-dominated immunopathogenesis, was analyzed. Zinc administration diminished EAE scores in C57BL/6 mice in vivo (P<.05), reduced Th17 RORγT(+) cells (P<.05) and significantly increased inducible iTreg cells (P<.05). While Th17 cells decreased systemically, iTreg cells accumulated in the central nervous system. Cumulatively, zinc supplementation seems to be capable to induce tolerance in unwanted immune reactions by increasing iTreg cells. This makes zinc a promising future tool for treating autoimmune diseases without suppressing the immune system. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Characteristics of Cytomegalovirus Uveitis in Immunocompetent Patients.

    PubMed

    Woo, Jyh Haur; Lim, Wee K; Ho, Su L; Teoh, Stephen C

    2015-01-01

    To present the clinical characteristics of patients with anterior uveitis who had evidence of cytomegalovirus (CMV) infection on polymerase chain reaction PCR-based assays for viral DNA in aqueous samples. This was a retrospective observational case series of 16 patients with CMV infection on qualitative polymerase chain reaction PCR-based assays for viral DNA in aqueous samples. Case records of 16 patients were reviewed and relevant clinical information was collected using a standardized data sheet. There were 10 male and 6 female patients, with 16 eyes included. The median age at the first attack was 52 years (range 27-77 years). Thirteen patients (81.3%) presented with an initial BCVA of 20/40 or better. Eleven eyes (68.8%) had anterior chamber inflammation of 1+ cells or less. Eight eyes (50.0%) had concomitant sectoral iris atrophy, while 2 eyes were noted to have heterochromic irides. Eleven patients (68.8%) presented with an elevated intraocular pressure. Seven patients (43.8%) had clinical features that led to a presumptive diagnosis of Posner-Schlossman syndrome, while 3 patients (18.8%) were initially diagnosed with Fuchs heterochromic iridocyclitis. Six patients were initially treated for uveitic glaucoma or anterior uveitis of unknown cause. There is a spectrum of clinical manifestations of CMV anterior uveitis. A high index of suspicion of a possible viral etiology, especially CMV, and subsequent accurate identification of the virus involved are fundamental to the overall therapeutic approach.

  17. Risk of Ocular Hypertension in Adults with Non-infectious Uveitis

    PubMed Central

    Daniel, Ebenezer; Pistilli, Maxwell; Kothari, Srishti; Khachatryan, Naira; Kaçmaz, R. Oktay; Gangaputra, Sapna S.; Sen, H. Nida; Suhler, Eric B.; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Levy-Clarke, Grace A.; Bhatt, Nirali P.; Kempen, John H.

    2017-01-01

    Objective To describe the risk and risk factors for ocular hypertension (OHT) in adults with non-infectious uveitis. Design Retrospective, multicenter, cohort study. Participants Patients aged ≥ 18 years with non-infectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics. Methods Demographic, ocular and treatment data were extracted from medical records of uveitis cases. Main outcome measures Prevalent and incident OHT with intraocular pressures (IOP) of ≥21 mmHg, ≥30mmHg and rise of ≥10 mmHg from documented IOP recordings (or use of treatment for OHT). Results Among 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT ≥21mmHg and OHT ≥30mmHg are 14.4% (95%CI: 13.4%, 15.5%) and 5.1% (95% CI: 4.7%, 5.6%) per year, respectively. Statistically significant risk factors for incident OHT ≥30mmHg included: systemic hypertension (adjusted hazard ratio (aHR) = 1.29); worse presenting visual acuity (20/200 or worse vs 20/40 or better, aHR = 1.47); pars plana vitrectomy (aHR = 1.87); prior history of OHT in the other eye: IOP ≥ 21 mmHg (aHR = 2.68), ≥30 mmHg (aHR=4.86), and prior/current use of IOP-lowering drops or surgery in the other eye (aHR = 4.17); anterior chamber cells: 1+ (aHR = 1.43) and ≥2+ (aHR = 1.59) vs none; epiretinal membrane (aHR=1.25); peripheral anterior synechiae (aHR = 1.81); current use of prednisone>7.5 mg/day (aHR = 1.86); periocular corticosteroids in the last three months (aHR = 2.23); current topical corticosteroid use [≥ 8X/day vs. none] (aHR=2.58); and prior use of fluocinolone acetonide implants (aHR = 9.75). Bilateral uveitis (aHR = 0.69) and previous hypotony (aHR=0.43) were associated with statistically significantly lower risk of OHT. Conclusions OHT is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with one or more of the several risk factors identified are at particularly high risk

  18. Interferon alpha-2a treatment for refractory Behcet uveitis in Korean patients.

    PubMed

    Lee, Ji Hwan; Lee, Christopher Seungkyu; Lee, Sung Chul

    2018-02-20

    To evaluate therapeutic outcomes of interferon alpha-2a (IFNα2a) treatment in patients with Behcet's disease who were refractory to immunosuppressive agents. This retrospective case series reviewed the medical records of 5 patients with refractory Behcet uveitis from January 2011 to February 2017. IFNα2a was administered at a dose of 3 million IU 3 times per week. Clinical response, relapse rate, and change of visual acuity were evaluated. The mean age of patients was 39.60 ± 9.21 years, and the median treatment duration was 6 months. Four of the 5 patients (80%) presented with responses to IFNα2a without any uveitis attack during the treatment period. The mean number of uveitis attacks/year per patient during the treatment was 0.40 ± 0.89. The mean log of the Minimum Angle of Resolution visual acuity improved from 1.44 ± 0.38 at baseline to 1.02 ± 0.58 at the final follow up. IFNα2a is an effective therapy for Behcet uveitis refractory to conventional immunosuppressants in Korean patients.

  19. Diagnosis and treatment for ocular tuberculosis among uveitis specialists: the international perspective.

    PubMed

    Lou, Susan M; Montgomery, Paul A; Larkin, Kelly L; Winthrop, Kevin; Zierhut, Manfred; Rosenbaum, James T

    2015-02-01

    To assess the approach of international specialists, who primarily practice in tuberculosis-endemic areas, to ocular tuberculosis (TB). International experts from India, Brazil, Taiwan, and more than 10 other countries were surveyed using two clinical cases and general questions. A total of 244 experts were sent a survey about the treatment and diagnosis of ocular tuberculosis; 65 responded (27%), of whom 34 were affiliated with practices in India, while 31 primarily practice at international sites outside of India and North America. The data from this survey were compared with the results of a similar survey sent to members of the American Uveitis Society. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on topics such as tests to include in the workup of undifferentiated uveitis, initial therapy, and duration of treatment. Physicians from developing countries relied more on chest CT scans and tuberculin skin testing (TST) than their counterparts in developed countries. The approach to diagnosis and management of TB is heterogeneous worldwide. However, there are substantial differences in the clinical approach to uveitis depending on the clinician's location of practice.

  20. Association of genetic variants in RAB23 and ANXA11 with uveitis in sarcoidosis

    PubMed Central

    Davoudi, Samaneh; Chang, Victoria S.; Navarro-Gomez, Daniel; Stanwyck, Lynn K.; Sevgi, Damla Duriye; Papavasileiou, Evangelia; Ren, Aiai; Uchiyama, Eduardo; Sullivan, Lynn; Lobo, Ann-Marie; Papaliodis, George N.

    2018-01-01

    Purpose Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis. Methods Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK. Results SNPs rs1040461 and rs61860052, in ras-related protein RAS23 (RAB23) and annexin A11 (ANXA11) genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in HLA-DRB5 and HLA-DRB1, were associated with uveitis as well (p=0.009 and p=0.04). Conclusions Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk. PMID:29416296

  1. The use of low dose methotrexate in children with chronic anterior and intermediate uveitis.

    PubMed

    Malik, A R; Pavesio, C

    2005-07-01

    To assess the efficacy of low dose methotrexate (MTX) therapy for children with chronic anterior and intermediate uveitis. A retrospective case review of 10 children who received MTX for chronic uveitis at a tertiary referral centre was performed. The following data were recorded for each patient: age, sex, race, duration of uveitis, primary diagnosis, anatomical localisation of uveitis, corticosteroid therapy, dose range of MTX, duration of MTX therapy, and side effects of MTX therapy. Several clinical parameters were evaluated to study the effect of MTX. These included visual acuity, anterior chamber inflammation, and topical and oral corticosteroid requirement. After MTX VA of 6/6 or better was present in 100% right eyes and 80% left eyes (p = 0.055 and p = 0.016, respectively). Anterior chamber inflammation decreased in 60% of children after MTX (p = 0.0168). The requirement of topical steroid decreased from a mean of 5.6 times a day before MTX to 1.5 times a day after MTX (p = 0.005). The dose of oral steroid decreased from a mean of 18 mg per day to 2.85 mg per day (p = 0.012). The most common adverse effect was nausea (20%). No patient required discontinuation of MTX because of side effects. MTX is effective and safe for chronic anterior and intermediate uveitis in children. An increase awareness of its efficacy is required among paediatricians and ophthalmologists to prevent sight threatening complication of chronic uveitis and its treatment with long term use of steroids.

  2. The use of low dose methotrexate in children with chronic anterior and intermediate uveitis

    PubMed Central

    Malik, A R; Pavesio, C

    2005-01-01

    Aim: To assess the efficacy of low dose methotrexate (MTX) therapy for children with chronic anterior and intermediate uveitis. Methods: A retrospective case review of 10 children who received MTX for chronic uveitis at a tertiary referral centre was performed. The following data were recorded for each patient: age, sex, race, duration of uveitis, primary diagnosis, anatomical localisation of uveitis, corticosteroid therapy, dose range of MTX, duration of MTX therapy, and side effects of MTX therapy. Several clinical parameters were evaluated to study the effect of MTX. These included visual acuity, anterior chamber inflammation, and topical and oral corticosteroid requirement. Results: After MTX VA of 6/6 or better was present in 100% right eyes and 80% left eyes (p = 0.055 and p = 0.016, respectively). Anterior chamber inflammation decreased in 60% of children after MTX (p = 0.0168). The requirement of topical steroid decreased from a mean of 5.6 times a day before MTX to 1.5 times a day after MTX (p = 0.005). The dose of oral steroid decreased from a mean of 18 mg per day to 2.85 mg per day (p = 0.012). The most common adverse effect was nausea (20%). No patient required discontinuation of MTX because of side effects. Conclusion: MTX is effective and safe for chronic anterior and intermediate uveitis in children. An increase awareness of its efficacy is required among paediatricians and ophthalmologists to prevent sight threatening complication of chronic uveitis and its treatment with long term use of steroids. PMID:15965154

  3. [Mycotic keratitis with uveitis cause by Scedosporium apiospermum].

    PubMed

    Firdová, M; Tkácová, E; Jesenská, Z; Minová, M

    1997-08-01

    Mycotic Keratitis with Induced Uveitis Caused by Scedosporium Apiospermum. In the work the case of mycotic keratitis with induced uveitis is descriped. Affected is young healthy woman working in a fruit and vegetable store. Affection arised on cornea in the area of previous erosion. Current antibiotics did not have any effect on the affection after repeated negative cultivative examinations. The culture of fibrous mikromycete was gained out of cultivation done on Sabouraud's glucose agar and was identified as Scedosporium apiospermum. This is the first case of mycotic eye infection of this etiology in our conditions. The patient reacted successfully on miconazol treatment. The finding on cornea equals vascularized leucoma, visual acuity is 5/50. In the future perforative keratoplastic is planned.

  4. Long-term effects of tocilizumab therapy for refractory uveitis-related macular edema.

    PubMed

    Mesquida, Marina; Molins, Blanca; Llorenç, Victor; Sainz de la Maza, Maite; Adán, Alfredo

    2014-12-01

    To report the long-term efficacy and safety of the interleukin-6 receptor antagonist tocilizumab for refractory uveitis-related macular edema (ME). Retrospective cohort study. Eyes with uveitis seen at a single tertiary referral center for which ME was the principal cause of reduced visual acuity. Data were obtained by standardized chart review. Central foveal thickness (CFT) measured by optical coherence tomography, degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), and visual acuity (logarithm of the minimum angle of resolution [logMAR]) were recorded during tocilizumab therapy at months 1, 3, 6, and 12. Eleven eyes from 7 patients (all women) were included. Mean age was 43.4 years. Mean duration of ME was 14.2 years. Mean follow-up with tocilizumab therapy was 15.2 months (range, 12-18 months). Before tocilizumab therapy, conventional immunosuppressive therapy and 1 or more biologic agents failed in all patients. Uveitis diagnoses were birdshot chorioretinopathy (n = 3), juvenile idiopathic arthritis-associated uveitis (n = 3), and idiopathic panuveitis (n = 1). Mean CFT was 550 ± 226 μm at baseline, 389 ± 112 μm at month 1 (P = 0.007), 317 ± 88 μm at month 3 (P = 0.01), 292 ± 79 μm at month 6 (P = 0.006), and 274 ± 56 μm at month 12 of follow-up (P = 0.002). Mean logMAR best-corrected visual acuity improved from 0.67 ± 0.53 at baseline to 0.4 ± 0.56 at month 12 (P = 0.008). Tocilizumab therapy was withdrawn in 2 patients because of sustained remission at month 12. In both patients, ME relapsed 3 months after tocilizumab withdrawal. Reinitiation of tocilizumab therapy led to good uveitis control and ME resolution. Tocilizumab generally was well tolerated and no serious adverse events were reported. In this study, tocilizumab was effective in the treatment of refractory inflammatory ME. No serious adverse events were observed. Copyright © 2014 American Academy of Ophthalmology

  5. Stimulated-single fiber electromyography monitoring of anti-sense induced changes in experimental autoimmune myasthenia gravis.

    PubMed

    Boneva, Neli; Hamra-Amitay, Yasmine; Wirguin, Itzhak; Brenner, Talma

    2006-05-01

    The neuromuscular weakness associated with myasthenia gravis (MG) can be transiently relieved by pharmacological inhibitors of acetylcholinesterase (AChE). Here, we expand the anticholinesterase repertoire to include 2'-O-methyl-protected antisense oligonucleotides targeted to AChE mRNA (EN101). Using stimulated-single fiber electromyography, we show that EN101 treatment of rats with experimental autoimmune myasthenia gravis (EAMG), improved the mean consecutive difference (MCD) and blocking for 24h. This treatment was more efficient than pyridostigmine and was accompanied by marked improvement in stamina and clinical profile.

  6. Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry.

    PubMed

    Foeldvari, Ivan; Becker, Ingrid; Horneff, Gerd

    2015-11-01

    Uveitis is a major extraarticular quality of life-restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX). Patients' characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated. Uveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58-2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient-years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient-years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient-years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3-3.8) while taking etanercept and 1.8 years (IQR 1.8-2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3-10.0) in the etanercept cohort and 4.8 years (IQR 1.0-5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis. Patients with a history of uveitis had higher risks for

  7. Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

    PubMed

    Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

    2016-11-08

    Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

  8. Roles of macrophage migration inhibitory factor in Guillain-Barré syndrome and experimental autoimmune neuritis: beneficial or harmful?

    PubMed

    Shen, Donghui; Lang, Yue; Chu, Fengna; Wu, Xiujuan; Wang, Ying; Zheng, Xiangyu; Zhang, Hong-Liang; Zhu, Jie; Liu, Kangding

    2018-06-11

    Macrophage migration inhibitory factor (MIF) plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN), which may offer an opportunity for the development of the novel therapeutic strategies for GBS. Areas covered: 'macrophage migration inhibitory factor' and 'Guillain-Barré syndrome' were used as keywords to search for related publications on Pub-Med, National Center for Biotechnology Information (NCBI), USA. MIF is involved in the etiology of various inflammatory and autoimmune disorders. However, the roles of MIF in GBS and EAN have not been summarized in the publications we identified. Therefore, in this review, we described and analyzed the major roles of MIF in GBS/EAN. Primarily, this molecule aggravates the inflammatory responses in this disorder. However, multiple studies indicated a protective role of MIF in GBS. The potential of MIF as a therapeutic target in GBS has been recently demonstrated in experimental and clinical studies, although clinical trials have been unavailable to date. Expert opinion: MIF plays a critical role in the initiation and progression of GBS and EAN, and it may represent a potential therapeutic target for GBS.

  9. Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis.

    PubMed

    Lazaridis, Konstantinos; Dalianoudis, Ioannis; Baltatzidi, Vasiliki; Tzartos, Socrates J

    2017-11-15

    Myasthenia gravis (MG) is caused by autoantibodies, the majority of which target the muscle acetylcholine receptor (AChR). Plasmapheresis and IgG-immunoadsorption are useful therapy options, but are highly non-specific. Antigen-specific immunoadsorption would remove only the pathogenic autoantibodies, reducing the possibility of side effects while maximizing the benefit. We have extensively characterized such adsorbents, but in vivo studies are missing. We used rats with experimental autoimmune MG to perform antigen-specific immunoadsorptions over three weeks, regularly monitoring symptoms and autoantibody titers. Immunoadsorption was effective, resulting in a marked autoantibody titer decrease while the immunoadsorbed, but not the mock-treated, animals showed a dramatic symptom improvement. Overall, the procedure was found to be efficient, suggesting the subsequent initiation of clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Intraocular Levels of Interleukin 17A (IL-17A) and IL-10 as Respective Determinant Markers of Toxoplasmosis and Viral Uveitis

    PubMed Central

    Villard, Odile; Creuzot-Garcher, Catherine; Chiquet, Christophe; Berrod, Jean-Paul; Speeg-Schatz, Claude; Bourcier, Tristan; Candolfi, Ermanno

    2014-01-01

    Uveitis is a potentially blinding inflammatory disease. Thirty to 50% of uveitis cases are considered idiopathic. The present study sought to determine the intraocular cytokine patterns in the different etiological types of uveitis in order to better understand their immunological regulation and to determine whether the cytokine pattern may be a useful diagnostic tool. From a multicenter institutional prospective study, the clinical and biological data from patients with uveitis of various etiologies, determined after a complete workup, were compared with those from a control group of cataract patients. A multiplex assay was used to assess the profiles of 27 cytokines and chemokines in aqueous humor samples from these patients. In total, 62 patients with infectious or noninfectious uveitis and 88 controls were included. After a complete workup, the cause of uveitis remained unknown in 25 patients (40% idiopathic uveitis). Interleukin 1β (IL-1β) levels were markedly increased in viral uveitis, as were IL-10 levels, whereas IL-17A levels were augmented in toxoplasmic uveitis. Based on the cytokine pattern, the patients were reassigned to specific groups. At the end of the study, the diagnosis of idiopathic uveitis was still valid in only 11 patients (18%). The observation that some markers are specific to certain diseases enables a better understanding of the disease pathogenesis and paves the way for new diagnostic methods aimed to identify inflammatory markers, which may perhaps be targeted by therapy. PMID:25378353

  11. Serological study of leptospiral infections and endogenous uveitis among horses and ponies in the United Kingdom.

    PubMed

    Matthews, A G; Waitkins, S A; Palmer, M F

    1987-03-01

    The prevalence of antibody titres to a range of 20 leptospira antigens in the serum of horses and ponies with no ophthalmic abnormalities and with ophthalmoscopic evidence of endogenous uveal inflammatory disease was determined using a microscopic agglutination technique. Titres against leptospira antigens were observed in 13 out of 138 (9.1 per cent) animals with no ophthalmic abnormalities, and in three out of 27 (11.1 per cent) animals with anterior uveitis. Serovar sejroe was common to all seropositive animals with anterior uveitis. The results show that leptospira infection is not a major factor in the aetiology of equine anterior uveitis in the UK, but suggests that the organism may be associated with some cases of recurrent anterior uveitis.

  12. Progress in the understanding and utilization of biologic response modifiers in the treatment of uveitis.

    PubMed

    Maleki, Arash; Meese, Halea; Sahawneh, Haitham; Foster, C Stephen

    2016-07-01

    Uveitis is the third most common cause of blindness in developed countries. Considering the systemic and local complications of long-term corticosteroid therapy and the intolerance due to side effects and ineffectiveness of conventional chemotherapy, use of biologic response modifiers is a reasonable alternative in the treatment of non-infectious uveitis and persistent uveitic macular edema. The majority of the evidence presented here comes from open uncontrolled analyses. Based on these studies, tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, have been shown to be effective in the treatment of non-infectious uveitis in numerous studies. More research is necessary, particularly multi-center randomized clinical trials, to address the choice of biologic response modifier agent and the length of treatment as we employ biologic response modifiers in different types of uveitis and persistent uveitic macular edema.

  13. Chemokine gene polymorphisms associate with gender in patients with uveitis.

    PubMed

    Chen, Y; Vaughan, R W; Kondeatis, E; Fortune, F; Graham, E M; Stanford, M R; Wallace, G R

    2004-01-01

    Uveitis is an inflammatory condition of ocular tissue characterized by leukocyte infiltration, tissue damage, and decreased visual acuity. Chemokines have been implicated in the pathogenesis of uveitis. Polymorphisms in the genes encoding chemokines have been described as affecting chemokine production or function. We analyzed the frequency of single-nucleotide polymorphisms (SNPs) in genes encoding CCL2 (-2518 and -2076) and CCL5 (-403 and -28) in patients with Behçet's disease (BD), a systemic form of uveitis, and patients with retinal vasculitis (RV), an organ-specific form of disease. We report that there was no association between any SNP and disease. However, when segregated on the basis of gender the CCR5 -403 AA genotype was only found in male patients with BD. Similarly, CCL2 genotypes 1/2 were predominant in males, while genotype 4 was significantly associated with disease in female patients with BD. Differences in disease symptoms and severity between males and females have been described in BD and gender-specific genetic differences in chemokine gene function may be involved.

  14. Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis.

    PubMed

    Hedayatfar, Alireza; Falavarjani, Khalil Ghasemi; Soheilian, Masoud; Elmi Sadr, Navid; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Rohani, Mohammad; Almasi, Mostafa; Chee, Soon-Phaik

    2017-06-01

    To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.

  15. Treatment of juvenile idiopathic arthritis-associated uveitis: challenges and update.

    PubMed

    Rabinovich, C Egla

    2011-09-01

    To update the current understanding of the risk factors for poor outcomes in juvenile idiopathic arthritis-related uveitis. In addition, current therapies, both traditional and biological, are reviewed. Male sex, independent of age or antinuclear antibody status, is associated with increased ocular morbidity. Having anterior chamber inflammation on first exam increases the risk of developing vision-threatening eye complications. Presence of one complication increases the risk of developing another. Risk of cataract development associated with topical glucocorticoid use is better defined. Longer duration of remission on therapy has been found to decrease the risk of disease flare after discontinuation of methotrexate. Recent studies of both nonbiological and biological therapies for arthritis-related uveitis are discussed. With a better understanding of risk factors associated with the ocular morbidity of uveitis associated with juvenile idiopathic arthritis, aggressive therapies can be targeted for improved visual outcomes. Alternative treatments to avoid long-term corticosteroid use include the use of antimetabolites and biological therapies. More prospective comparator studies and/or use of multicenter databases are needed to better understand best treatments.

  16. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice.

    PubMed

    Schmitz, Katja; de Bruin, Natasja; Bishay, Philipp; Männich, Julia; Häussler, Annett; Altmann, Christine; Ferreirós, Nerea; Lötsch, Jörn; Ultsch, Alfred; Parnham, Michael J; Geisslinger, Gerd; Tegeder, Irmgard

    2014-11-01

    R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Effect and Mechanism of QiShenYiQi Pill on Experimental Autoimmune Myocarditis Rats

    PubMed Central

    Lv, Shichao; Wu, Meifang; Li, Meng; Wang, Qiang; Xu, Ling; Wang, Xiaojing; Zhang, Junping

    2016-01-01

    Background To observe the effect of QiShenYiQi pill (QSYQ) on experimental autoimmune myocarditis rats, and to explore its mechanism of action. Material/methods Lewis rats underwent the injection of myocardial myosin mixed with Freund’s complete adjuvant were randomized into 3 groups: model, valsartan, and QSYQ groups. Rats injected with phosphate-buffered saline (PBS) mixed with Freund’s complete adjuvant were used as the control group. Rats were euthanized at 4 and 8 weeks, and we weighed rat body mass, heart mass, and left ventricular mass. Myocardium sections were stained with hematoxylin and eosin (H&E) and Masson trichrome. Myocardial TGF-β1 and CTGF protein expression was detected by immunohistochemistry, and myocardial TGF-β1 and CTGF mRNA expression was detected by real-time qPCR. Results QSYQ reduced HMI and LVMI, as well as the histological score of hearts and CVF, which further decreased over time, and its effect was significantly greater than that of valsartan at 4 and 8 weeks. After 4 weeks, QSYQ inhibited the protein and mRNA expression of TGF-β1 and CTGF, and its effect on lowering CTGF was significantly greater than that of valsartan. In addition, after 8 weeks, QSYQ also inhibited the protein and mRNA expression of CTGF, whereas there was no significant difference in the expression of myocardial TGF-β1. Conclusions This study provides evidence that QSYQ can improve cardiac remodeling of experimental autoimmune myocarditis rats. It also effectively improved the degree of myocardial fibrosis, which is related to the mechanism of regulation of TGF-β1 CTGF. PMID:26946470

  18. Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.

    PubMed

    Sasajima, Hirofumi; Yagi, Syunsuke; Osada, Hiromu; Zako, Masahiro

    2017-05-04

    Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.

  19. Clinical Remission of Sight-Threatening Non-Infectious Uveitis Is Characterized by an Upregulation of Peripheral T-Regulatory Cell Polarized Towards T-bet and TIGIT.

    PubMed

    Gilbert, Rose M; Zhang, Xiaozhe; Sampson, Robert D; Ehrenstein, Michael R; Nguyen, Dao X; Chaudhry, Mahid; Mein, Charles; Mahmud, Nadiya; Galatowicz, Grazyna; Tomkins-Netzer, Oren; Calder, Virginia L; Lightman, Sue

    2018-01-01

    Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4 + CD25 + FoxP3 + T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission. To investigate whether there is a peripheral blood immunoregulatory phenotype associated with clinical remission of sight-threatening non-infectious uveitis by comparing peripheral blood levels of Treg, Th1, and Th17, and associated DNA methylation and cytokine levels in patients with active uveitic disease, control subjects and patients (with previously active disease) in clinical remission induced by immunosuppressive drugs. Isolated peripheral blood mononuclear cells (PBMC) from peripheral blood samples from prospectively recruited subjects were analyzed by flow cytometry for CD3, CD4, FoxP3, TIGIT, T-bet, and related orphan receptor γt. Epigenetic DNA methylation levels of FOXP3 Treg-specific demethylated region (TSDR), FOXP3 promoter, TBX21, RORC2, and TIGIT loci were determined in cryopreserved PBMC using a next-generation sequencing approach. Related cytokines were measured in blood sera. Functional suppressive capacity of Treg was assessed using T-cell proliferation assays. Fifty patients with uveitis (intermediate, posterior, and panuveitis) and 10 control subjects were recruited. The frequency of CD4 + CD25 + FoxP3 + Treg, TIGIT + Treg, and T-bet + Treg and the ratio of Treg to Th1 were significantly higher in remission patients compared with patients with active uveitic disease; and TIGIT + Tregs were a significant predictor of clinical remission. Treg from patients in clinical remission demonstrated a high level of in vitro suppressive function compared with Treg from

  20. An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis.

    PubMed

    Sood, Arjun B; Angeles-Han, Sheila T

    2017-03-01

    There are no standardized treatment protocols for pediatric non-infectious uveitis. Topical corticosteroids are the typical first-line agent, although systemic corticosteroids are used in intermediate, posterior and panuveitic uveitis. Corticosteroids are not considered to be long-term therapy due to potential ocular and systemic side effects. In children with severe and/or refractory uveitis, timely management with higher dose disease-modifying antirheumatic drugs (DMARDs) and biologic agents is important. Increased doses earlier in the disease course may lead to improved disease control and better visual outcomes. In general, methotrexate is the usual first-line steroid-sparing agent and given as a subcutaneous weekly injection at >0.5 mg/kg/dose or 10-15 mg/m2 due to better bioavailability. Other DMARDs, for instance mycophenolate, azathioprine, and cyclosporine are less common treatments for pediatric uveitis. Anti-tumor necrosis factor-alpha agents, primarily infliximab and adalimumab are used as second line agents in children refractory to methotrexate, or as first-line treatment in those with severe complicated disease at presentation. Infliximab may be given at a minimum of 7.5 mg/kg/dose every 4 weeks after loading doses, up to 20 mg/kg/dose. Adalimumab may be given up to 20 or 40 mg weekly. In children who fail anti-tumor necrosis factor-alpha agents, develop anti-tumor necrosis factor-alpha antibodies, experience adverse effects, or have difficulty with tolerance, there is less data available regarding subsequent treatment. Promising results have been noted with tocilizumab infusions every 2-4 weeks, abatacept monthly infusions and rituximab.

  1. An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis

    PubMed Central

    Sood, Arjun B.; Angeles-Han, Sheila T.

    2017-01-01

    Opinion Statement There are no standardized treatment protocols for pediatric non-infectious uveitis. Topical corticosteroids are the typical first-line agent, although systemic corticosteroids are used in intermediate, posterior and panuveitic uveitis. Corticosteroids are not considered to be long-term therapy due to potential ocular and systemic side effects. In children with severe and/or refractory uveitis, timely management with higher dose disease-modifying antirheumatic drugs (DMARDs) and biologic agents is important. Increased doses earlier in the disease course may lead to improved disease control and better visual outcomes. In general, methotrexate is the usual first-line steroid-sparing agent and given as a subcutaneous weekly injection at >0.5 mg/kg/dose or 10–15 mg/m2 due to better bioavailability. Other DMARDs, for instance mycophenolate, azathioprine, and cyclosporine are less common treatments for pediatric uveitis. Anti-tumor necrosis factor-alpha agents, primarily infliximab and adalimumab are used as second line agents in children refractory to methotrexate, or as first-line treatment in those with severe complicated disease at presentation. Infliximab may be given at a minimum of 7.5 mg/kg/dose every 4 weeks after loading doses, up to 20 mg/kg/dose. Adalimumab may be given up to 20 or 40 mg weekly. In children who fail anti-tumor necrosis factor-alpha agents, develop anti-tumor necrosis factor-alpha antibodies, experience adverse effects, or have difficulty with tolerance, there is less data available regarding subsequent treatment. Promising results have been noted with tocilizumab infusions every 2–4 weeks, abatacept monthly infusions and rituximab. PMID:28944162

  2. Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up.

    PubMed

    Ardoin, Stacy P; Kredich, Deborah; Rabinovich, Egla; Schanberg, Laura E; Jaffe, Glenn J

    2007-12-01

    To assess a response to infliximab therapy in childhood uveitis. Retrospective case series. We reviewed the course of 16 children with noninfectious uveitis treated with infliximab at an academic medical center. Outcome measures included incidence of uveitis recurrences, proportion of patients achieving zero or two-step decline in ocular inflammation, visual acuity, and proportion discontinuing topical glucocorticoids at zero, three, six, nine, and 12 months of therapy. Of sixteen children (29 affected eyes) with median age 11 years, six had associated extraocular inflammatory conditions. Fifteen of 16 were treated with concomitant methotrexate. Median follow-up was 26 months and median maintenance infliximab dose was 8.2 mg/kg. The median interval between infliximab infusions was 5.6 weeks. At one year, 64% achieved zero ocular inflammation, and 79% had zero inflammation or a two-step decline in inflammation. Topical glucocorticoids were discontinued in 69%, and 58% remained free of uveitis recurrence at one year. Visual acuity remained stable. Infliximab was discontinued in two children, one because of inefficacy and the other because of parental concern about potential side effects. No adverse events occurred. Sixteen children with chronic, noninfectious uveitis tolerated chronic methotrexate and infliximab therapy. Visual acuity remained stable, control of ocular inflammation improved, and reliance on topical glucocorticoids decreased. High infliximab doses and frequent dosing intervals were necessary to control uveitis.

  3. Uveitis-Glaucoma-Hyphaema Syndrome. General review.

    PubMed

    Zemba, Mihail; Camburu, Georgiana

    2017-01-01

    Uveitis-Glaucoma-Hyphaema Syndrome (UGH syndrome, or "Ellingson" Syndrome) is a rare condition caused by the mechanical trauma of an intraocular lens malpositioned over adjacent structures (iris, ciliary body, iridocorneal angle), leading to a spectrum of iris transillumination defects, microhyphaemas and pigmentary dispersion, concomitant with elevated intraocular pressure (IOP). UGH Syndrome can also be characterized by chronic inflammation, secondary iris neovascularization, cystoid macular edema (CME). The fundamental step in the pathogenesis of UGH syndrome appears to arise from repetitive mechanical iris trauma by a malpositioned or subluxed IOL. These patients have uncomplicated cataract implants and return for episodes of blurry vision weeks to months after surgery. This may be accompanied by pain, photophobia, erythropsia, anterior uveitis, hyphaema along with raised intraocular pressure. A careful history and examination, as well as appropriate investigations can confirm the diagnostic. Treatment options are IOL Explantation exchange, topical and systemic medication, and cyclophotocoagulation, the placement of a Capsular Tension Ring to redistribute zonular tension and Anti-vascular endothelial growth factor (anti-VEGF) Therapy.

  4. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

    PubMed

    Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

    2015-05-01

    Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared

  5. Characterization of uveitis induced by use of a single intravitreal injection of bacterial lipopolysaccharide in cats.

    PubMed

    Del Sole, María J; Sande, Pablo H; Felipe, Antonio E; Fernandez, Diego C; Keller Sarmiento, María I; Aba, Marcelo A; Rosenstein, Ruth E

    2008-11-01

    To investigate the use of a single intravitreal injection of bacterial lipopolysaccharide (LPS) to experimentally induce uveitis in cats. 7 young male European shorthair cats that were considered physically and ophthalmologically healthy. In each cat, LPS was injected intravitreally into 1 eye; the contralateral eye was injected with the preparation vehicle. During a period of 45 days, both eyes were evaluated by means of clinical evaluation; assessment of the integrity of the blood-aqueous humor barrier (determined via measurement of protein concentration and cell content in samples of aqueous humor); functional analysis (via electroretinography); and following euthanasia, histologic examination of the retinas. In LPS-treated eyes, several clinical signs were observed until day 45 after injection. Compared with vehicle-treated eyes, intraocular pressure was significantly lower and protein concentration and the number of infiltrating cells were significantly higher in LPS-treated eyes. Mean amplitudes of scotopic electroretinographic a- and b-waves were significantly reduced in eyes injected with LPS, compared with findings in eyes injected with vehicle. At 45 days after injection, LPS-induced alterations in photoreceptors and the middle portion of the retina were detected histologically. Results indicated that a single intravitreal injection of LPS in eyes of cats induced clinical, biochemical, functional, and histologic changes that were consistent with the main features of naturally occurring uveitis. This technique may be a useful tool in the investigation of new treatment strategies for uveitis in cats.

  6. Retrospective Study Evaluating Treatment Decisions and Outcomes of Childhood Uveitis Not Associated with Juvenile Idiopathic Arthritis.

    PubMed

    Sardar, Elham; Dusser, Perrine; Rousseau, Antoine; Bodaghi, Bahram; Labetoulle, Marc; Koné-Paut, Isabelle

    2017-07-01

    To evaluate treatment, ocular complications and outcomes of children with pediatric uveitis not associated with juvenile idiopathic arthritis. This was a retrospective chart review of pediatric uveitis in children under 16 years of age, recruited from the pediatric rheumatology department at Bicêtre Hospital from 2005 to 2015. Patients with juvenile idiopathic arthritis-associated and infectious uveitis were excluded. We used the Standardization of Uveitis Nomenclature Working Group to classify uveitis, disease activity, and treatment end points. We enrolled 56 patients and 102 affected eyes. The mean age at diagnosis was 10 ± 3.5 years (range 3-15), and the mean follow-up 4.2 ± 3.3 years (1-15). The main diagnoses were idiopathic (55%), Behçet disease (15%), and sarcoidosis (5%). The main localization was panuveitis in 44 of 102 eyes (43%). Corticosteroid sparing treatment was needed in 62 of 102 eyes (60%). Second-line therapies included methotrexate and azathioprine, and the third-line therapy was a biologic agent, mainly infliximab, in 33 of 102 eyes (32%). Infliximab achieved uveitis inactivity in 14 of 18 eyes (80%), in all etiologies. Severe complications were present in 68 of 102 eyes (67%). The most common were synechiae 33% of eyes, cataract (20%), and macular edema (25%). Of these, 37% were present at diagnosis. Remission was achieved in 22 of 102 eyes (21%). Conventional therapies were insufficient to treat many of the cases of posterior or panuveitis. This study underlines the need for earlier and more aggressive treatment and antitumor necrosis factor-α therapy was rapidly efficient in most cases of refractory uveitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry.

    PubMed

    Henderson, Lauren A; Zurakowski, David; Angeles-Han, Sheila T; Lasky, Andrew; Rabinovich, C Egla; Lo, Mindy S

    2016-02-16

    There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis. This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher's exact tests were used to assess for associations between medications and clinical characteristics. Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients. Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts.

  8. mTOR-inhibiting pharmacotherapy for the treatment of non-infectious uveitis: a systematic review protocol.

    PubMed

    Blair, Joshua; Barry, Robert; Murray, Philip I; Moore, David J; Denniston, Alastair K

    2018-06-09

    Non-infectious uveitis represents a sub-type of intraocular inflammation often associated with disorders of immune dysregulation. If untreated, the intraocular inflammation may progress to severe visual impairment and blindness. Current treatment is heavily reliant on systemic corticosteroid, often at doses associated with severe side effects. There is a need for efficacious corticosteroid-sparing immunomodulatory therapy for these patients. Current immunomodulators include various immunosuppressants and biologics but mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus and everolimus) may also be contenders for this role. The systematic review proposed here will evaluate the evidence for the use of sirolimus and everolimus in the context of non-infectious uveitis. Standard systematic review methodology will be used to identify, select and extract data from any comparative or non-comparative study of mTOR inhibitors in patients with non-infectious uveitis excluding case reports. Searches of bibliographic databases (MEDLINE, EMBASE, The Cochrane Library and CINAHL) and clinical trials registers will be performed, with no restriction on language or date of publication. Translation of non-English language articles will be undertaken where necessary. The primary outcome of interest will be uveitis activity as measured by vitreous haze. Secondary outcomes will include other pre-specified measures of uveitis activity (such as anterior chamber cells or central macular thickness) best corrected visual acuity, heath-related quality of life, requirement for concurrent treatment and adverse events. Risk of bias assessment will be performed appropriate to each study design. Study selection, data extraction and risk of bias assessment will be undertaken by two reviewers independently. Data will be grouped, tabulated and narratively synthesised. Meta-analysis will be undertaken where appropriate clinical and methodological homogeneity exists. The review will be

  9. Oral testosterone in male rats and the development of experimental autoimmune encephalomyelitis.

    PubMed

    Macció, Daniela R; Calfa, Gastón; Roth, German A

    2005-01-01

    Considering that sex steroids can influence the immune system, we studied the development of experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of the central nervous system, and the concomitant cell-mediated immunity in gonadally intact and gonadectomized male Wistar rats given testosterone supplementation. Sham-operated rats and surgically castrated animals were orally self-administered with vehicle or testosterone added in the water bottle for 20 days before EAE induction. The androgenic effect of oral testosterone self-administration was evidenced by changes in body weight, and in the weights of androgen-dependent testes and seminal vesicles. Testosterone administration reduced the incidence of clinical signs of EAE in sham-operated animals and reversed the clinical symptoms of the disease associated with castrated EAE animals. The clinical signs observed in the different groups correlated with changes in delayed-type hypersensitivity and mononuclear cell-proliferative responses to the encephalitogenic myelin basic protein. Moreover, testosterone but not cholesterol supplementation in vitro suppressed the proliferative response of mononuclear cells to myelin basic protein suggesting that testosterone may affect specific immune functions through direct actions on immune cells. Finally, self-administration of testosterone induced also elevated corticosterone levels that in sham-operated rats correlated with the low incidence of the disease and in gonadectomized animals could be involved in the remission of clinical symptoms of EAE. These results suggest that orally self-administered testosterone can modulate specific cellular immune responses and serum corticosterone levels leading to changes in the development of EAE. Copyright 2005 S. Karger AG, Basel.

  10. Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats.

    PubMed

    Göncü, Tuğba; Oğuz, Elif; Sezen, Hatice; Koçarslan, Sezen; Oğuz, Halit; Akal, Ali; Adıbelli, Fatih Mehmet; Çakmak, Sevim; Aksoy, Nurten

    2016-01-01

    We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

  11. Identification of autoantigens in body fluids by combining pull-downs and organic precipitations of intact immune complexes with quantitative label-free mass spectrometry.

    PubMed

    Merl, Juliane; Deeg, Cornelia A; Swadzba, Margarete E; Ueffing, Marius; Hauck, Stefanie M

    2013-12-06

    Most autoimmune diseases are multifactorial diseases and are caused by the immunological reaction against a number of autoantigens. Key for understanding autoimmune pathologies is the knowledge of the targeted autoantigens, both initially and during disease progression. We present an approach for autoantigen identification based on isolation of intact autoantibody-antigen complexes from body fluids. After organic precipitation of high molecular weight proteins and free immunoglobulins, released autoantigens were identified by quantitative label-free liquid chromatography mass spectrometry. We confirmed feasibility of target enrichment and identification from highly complex body fluid proteomes by spiking of a predefined antibody-antigen complex at low level of abundance. As a proof of principle, we studied the blinding disease autoimmune uveitis, which is caused by autoreactive T-cells attacking the inner eye and is accompanied by autoantibodies. We identified three novel autoantigens in the spontaneous animal model equine recurrent uveitis (secreted acidic phosphoprotein osteopontin, extracellular matrix protein 1, and metalloproteinase inhibitor 2) and confirmed the presence of the corresponding autoantibodies in 15-25% of patient samples by enzyme-linked immunosorbent assay. Thus, this workflow led to the identification of novel autoantigens in autoimmune uveitis and may provide a versatile and useful tool to identify autoantigens in other autoimmune diseases in the future.

  12. Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis complicated by neovascularization

    PubMed Central

    Kurup, Shree; Lew, Julie; Byrnes, Gordon; Yeh, Steven; Nussenblatt, Robert; Levy-Clarke, Grace

    2010-01-01

    Purpose To evaluate the therapeutic effect of intravitreal bevacizumab in patients with uveitis-associated choroidal/retinal neovascularization. Methods Two female patients (40 years, 15 years) with posterior uveitis, (one presumed ocular sarcoidosis, one lupus) were evaluated for neovascularization of the posterior segment. Both patients were given a single dose of 1.25 mg intravitreal bevacizumab. Results Significant anatomical and functional recovery was evident in both patients within a few weeks. Conclusion In selected uveitic patients, bevacizumab may be an option for managing neovascularization. PMID:18513266

  13. James Wardrop and equine recurrent uveitis.

    PubMed

    Paglia, Danielle T; Miller, Paul E; Dubielzig, Richard R

    2004-08-01

    James Wardrop should be remembered not only as one of the founders of ocular pathology but also for his contributions to the field of comparative ophthalmology. He described a "specific inflammation" that veterinarians today know as equine recurrent uveitis. As described by Wardrop in the 19th century, this condition is known today to eventually lead to blindness.

  14. Inter- and intramolecular epitope spreading in equine recurrent uveitis.

    PubMed

    Deeg, Cornelia A; Amann, Barbara; Raith, Albert J; Kaspers, Bernd

    2006-02-01

    To test the hypothesis that inter- and intramolecular spreading to S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP)-derived epitopes occurs in a spontaneous model of recurrent uveitis in the horse. The immune response of eight horses with equine recurrent uveitis (ERU) was compared with that of five control horses with healthy eyes. Lymphocytes derived from peripheral blood (PBLs) were tested every 8 weeks for their reactivity against S-Ag and various S-Ag and IRBP-derived peptides for 12 to 39 months (median, 22 months). During uveitic episodes, additional blood samples were analyzed. Intermolecular epitope spreading was detectable in all ERU cases during the study. Intramolecular spreading occurred in seven (of eight) horses with ERU. Fourteen relapses were analyzed during the observation period. Ten uveitic episodes were accompanied by neoreactivity to S-Ag or IRBP-derived peptides during the relapse. Shifts in the immune response profile were also detectable without any clinical signs of inflammation. Eye-healthy control horses were negative at all time points in the in vitro proliferation assays. Inter- and intramolecular spreading was detectable in a spontaneous model of recurrent uveitis. The shifts in immunoreactivity could account for the remitting-relapsing character of the disease.

  15. Visual impairment from uveitis in a reference hospital of Southeast Brazil: a retrospective review over a twenty years period.

    PubMed

    Silva, Luci Meire Pereira da; Muccioli, Cristina; Oliveira, Filipe de; Arantes, Tiago Eugênio; Gonzaga, Lucas Renó; Nakanami, Célia Regina

    2013-01-01

    To identify the frequency and causes of uveitis leading to visual impairment in patients referred to the Low Vision Service - Department of Ophthalmology - UNIFESP, over a twenty years period. In a retrospective study, medical records of 5,461 patients were reviewed. Data from the first clinical evaluation at the Low Vision Service were collected, patient's age, gender and cause of visual impairment were analyzed. Patients with uveitis had their chart reviewed for anatomical classification and clinical diagnosis. The mean age of the patients referred to the Low Vision Service was 42.86 years and the mean age of patients with uveitis diagnosis was 25.51 years. Retinal disorders were the most common cause of visual impairment (N=2,835 patients; 51.9%) followed by uveitis (862 patients, 15.7%). Uveitis was posterior in 792 patients (91.9% of uveitis) and toxoplasmosis was the most common diagnosis (765 patients, 88.7%). In our study, uveitis represents the second cause of visual impairment in patients referred for visual rehabilitation and toxoplasmic retinochoroiditis was the most common clinical diagnosis. It affects a young working age population with a relevant social and economic impact, but the early diagnosis and treatment can improve the quality of life of these patients.

  16. Adoptive Cellular Gene Therapy for the Treatment of Experimental Autoimmune Polychondritis Ear Disease.

    PubMed

    Zhou, Bin; Liao, Yonggan; Guo, Yunkai; Tarner, Ingo H; Liao, Chunfen; Chen, Sisi; Kermany, Mohammad Habiby; Tu, Hanjun; Zhong, Sen; Chen, Peijie

    2017-01-01

    In the past, the clinical therapy for autoimmune diseases, such as autoimmune polychondritis ear disease, was mostly limited to nonspecific immunosuppressive agents, which could lead to variable responses. Currently, gene therapy aims at achieving higher specificity and less adverse effects. This concept utilizes the adoptive transfer of autologous T cells that have been retrovirally transduced ex vivo to express and deliver immunoregulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40-expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only-treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in the inflamed earlobes of the mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T cells did not affect antigen-specific T-cell activation or systemic anti-CII Ab responses. However, IL-12p40-transduced T cells suppressed IFN-γ and augmented IL-4 production, indicating their potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation. © 2017 S. Karger AG, Basel.

  17. Insulinotropic and Anti-Inflammatory Effects of Rosiglitazone in Experimental Autoimmune Diabetes

    PubMed Central

    Awara, Wageh M.; El-Sisi, Alaa E.; El-Refaei, Mohamed; El-Naa, Mona M.; El-Desoky, Karima

    2005-01-01

    Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ). The anti-inflammatory and immunomodulating properties of PPAR-γ have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-α, IFN-γ and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression. PMID:17491689

  18. Identification of immunodominant epitopes of alpha-crystallins recognized by antibodies in sera of patients with uveitis.

    PubMed

    Doycheva, Deshka; Preuss, Beate; Deuter, Christoph; Zierhut, Manfred; Klein, Reinhild

    2012-02-01

    A high incidence of autoantibodies to lens proteins has been found in sera of patients with uveitis. We showed previously that the anti-lens antibodies reacted predominantly with α-crystallins. The aim of the present study was to identify immunodominant epitopes within the protein chains of human αA- and αB-crystallin. Epitope specificities of antibodies to αA- and αB-crystallin were examined by ELISA using synthetic overlapping peptides, spanning the entire length of both α-crystallins. The peptides consisted of 25 amino acid residues, with an overlap of at least eight amino acids each. The synthetic peptides were tested against sera of 110 patients with different uveitis forms, classified according to anatomical location of intraocular inflammation. Four immunodominant regions within the protein chains of αA- and αB-crystallin could be identified. These regions were recognized by antibodies in sera of 56% of uveitis patients. Anti-lens antibodies of IgG-type reacted preferentially with regions located at amino acid (aa) residues aa:69-93 and aa:137-161 of αA-crystallin as well as aa:69-110 and aa:137-161 of αB-crystallin. IgM antibodies recognized predominantly region aa:149-173 of αA-crystallin, and aa:69-110 and aa:151-175 of αB-crystallin. IgM antibodies directed to peptide aa:69-93 of αB-crystallin were found in sera of 30% of patients with intermediate uveitis. Four immunodominant B-cell epitopes within the protein chains of αA- and αB-crystallin have been identified; however, no clear correlation with the anatomically defined uveitis subtypes has been found except for intermediate uveitis. Whether there may be a correlation with uveitis forms with similar etiopathogenesis has to be evaluated in further studies.

  19. Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients.

    PubMed

    Calvo-Río, Vanesa; Blanco, Ricardo; Santos-Gómez, Montserrat; Rubio-Romero, Esteban; Cordero-Coma, Miguel; Gallego-Flores, Adela; Veroz, Raúl; Torre, Ignacio; Hernández, Félix Francisco; Atanes, Antonio; Loricera, Javier; González-Vela, M C; Palmou, Natalia; Hernández, José L; González-Gay, Miguel A

    2016-08-01

    To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Multicenter study of SpA-related uveitis refractory to at least 1 immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. A total of 15 patients (13 men/2 women; 18 affected eyes; mean age 39 ± 6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n = 8), psoriatic arthritis (n = 6) and non-radiographic axial SpA (n = 1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n = 13), sulfasalazine (n = 6), pulses of methylprednisolone (n = 4), azathioprine (n = 3), leflunomide (n = 2), and cyclosporine (n = 1). Overall, 10 of them had also been treated with TNF-α blockers; etanercept (n = 7), adalimumab (n = 7), infliximab (n = 6), and certolizumab (n = 1). GLM was given at the standard dose (50mg/sc/monthly) as monotherapy (n = 7) or in combination with conventional immunosuppressive drugs (n = 8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years [0 (0-0)] was significantly reduced compared to baseline findings [1 (0-3); p = 0.04]. The mean best corrected visual acuity value also improved (0.84 ± 0.3 at 2 years versus 0.62 ± 0.3 at baseline; p = 0.03). Only minor side effects were observed after a mean follow-up of 23 ± 7 months. Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Novel function of Extracellular matrix protein 1 in suppressing Th17 cell development in experimental autoimmune encephalomyelitis

    PubMed Central

    Su, Pan; Chen, Sheng; Zheng, Yu Han; Zhou, Hai Yan; Yan, Cheng Hua; Yu, Fang; Zhang, Ya Guang; He, Lan; Zhang, Yuan; Wang, Yanming; Wu, Lei; Wu, Xiaoai; Yu, Bingke; Ma, Li Yan; Yang, Zhiru; Wang, Jianhua; Zhao, Guixian; Zhu, Jinfang; Wu, Zhi-Ying; Sun, Bing

    2016-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by demyelination and axonal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model for human MS. While Th17 cells are important for the disease induction, Th2 cells are inhibitory in this process. Here, we report the effect of a Th2 cell product, extracellular matrix protein 1 (ECM1), on the differentiation of Th17 cells and the development of experimental autoimmune encephalomyelitis (EAE). Our results demonstrated that ECM1 administration from day 1 to day 7 following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo. Further mechanism study revealed that ECM1 could interact with αv integrin on DC cells and block the αv integrin-mediated activation of latent TGF-β, resulting in an inhibition of Th17 differentiation at early stage of EAE induction. Furthermore, overexpression of ECM1 in vivo significantly inhibited Th17 cell response and EAE induction in ECM1 transgenic mouse. Overall, our work has identified a novel function of ECM1 in inhibiting Th17 differentiation in the EAE model, suggesting that ECM1 may have a potential to be used in clinical applications for understanding the pathogenesis of MS and its diagnosis. PMID:27316685

  1. Impaired striatal GABA transmission in experimental autoimmune encephalomyelitis.

    PubMed

    Rossi, Silvia; Muzio, Luca; De Chiara, Valentina; Grasselli, Giorgio; Musella, Alessandra; Musumeci, Gabriele; Mandolesi, Georgia; De Ceglia, Roberta; Maida, Simona; Biffi, Emilia; Pedrocchi, Alessandra; Menegon, Andrea; Bernardi, Giorgio; Furlan, Roberto; Martino, Gianvito; Centonze, Diego

    2011-07-01

    Synaptic dysfunction triggers neuronal damage in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). While excessive glutamate signaling has been reported in the striatum of EAE, it is still uncertain whether GABA synapses are altered. Electrophysiological recordings showed a reduction of spontaneous GABAergic synaptic currents (sIPSCs) recorded from striatal projection neurons of mice with MOG((35-55))-induced EAE. GABAergic sIPSC deficits started in the acute phase of the disease (20-25days post immunization, dpi), and were exacerbated at later time-points (35, 50, 70 and 90dpi). Of note, in slices they were independent of microglial activation and of release of TNF-α. Indeed, sIPSC inhibition likely involved synaptic inputs arising from GABAergic interneurons, because EAE preferentially reduced sIPSCs of high amplitude, and was associated with a selective loss of striatal parvalbumin (PV)-positive GABAergic interneurons, which contact striatal projection neurons in their somatic region, giving rise to more efficient synaptic inhibition. Furthermore, we found also that the chronic persistence of pro-inflammatory cytokines were able, per se, to produce profound alterations of electrophysiological network properties, that were reverted by GABA administration. The results of the present investigation indicate defective GABA transmission in MS models depending from alteration of PV cells number and, in part, deriving from the effects of a chronic inflammation, and suggest that pharmacological agents potentiating GABA signaling might be considered to limit neuronal damage in MS patients. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies.

    PubMed

    Deitch, Iris; Amer, Radgonde; Tomkins-Netzer, Oren; Habot-Wilner, Zohar; Friling, Ronit; Neumann, Ron; Kramer, Michal

    2018-04-01

    This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. This included a retrospective cohort study. Children with uveitis treated with infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were identified by database search. Their medical records were reviewed for demographic data, clinical presentation, ocular complications, and visual outcome. Systemic side effects and the steroid-sparing effect of treatment were documented. The cohort included 24 patients (43 eyes) of whom 14 received infliximab and 10 received adalimumab after failing conventional immunosuppression therapy. Mean age was 9.3 ± 4.0 years. The most common diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by Behçet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n = 1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20 eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in 4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During the 12 months prior to biologic treatment, while on conventional immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45 logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic treatment, remaining stable thereafter. A full corticosteroid-sparing effect was demonstrated in 16 of the 19 patients (84.2%) for whom data were available. Treatment was well tolerated. Treatment of pediatric uveitis with anti-TNF-α agents may improve outcome while providing steroid-sparing effect, when conventional immunosuppression fails. The role of anti-TNF-α agents as first-line treatment should be further investigated in controlled prospective clinical trials.

  3. [Autoimmune hepatitis].

    PubMed

    Ostojić, Rajko

    2003-01-01

    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  4. Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

    PubMed

    Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Haskó, György; Čiháková, Daniela; Mechoulam, Raphael; Pacher, Pal

    2016-01-08

    Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors. Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T cell-infiltration, profound inflammatory response, fibrosis (measured by qRT-PCR, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.

  5. Dendritic cells exposed in vitro to TGF-β1 ameliorate experimental autoimmune myasthenia gravis

    PubMed Central

    YARILIN, D; DUAN, R; HUANG, Y-M; XIAO, B-G

    2002-01-01

    Experimental autoimmune myasthenia gravis (EAMG) is an animal model for human myasthenia gravis (MG), characterized by an autoaggressive T-cell-dependent antibody-mediated immune response directed against the acetylcholine receptor (AChR) of the neuromuscular junction. Dendritic cells (DC) are unique antigen-presenting cells which control T- and B-cell functions and induce immunity or tolerance. Here, we demonstrate that DC exposed to TGF-β1 in vitro mediate protection against EAMG. Freshly prepared DC from spleen of healthy rats were exposed to TGF-β1 in vitro for 48 h, and administered subcutaneously to Lewis rats (2 × 106DC/rat) on day 5 post immunization with AChR in Freund’s complete adjuvant. Control EAMG rats were injected in parallel with untreated DC (naive DC) or PBS. Lewis rats receiving TGF-β1-exposed DC developed very mild symptoms of EAMG without loss of body weight compared with control EAMG rats receiving naive DC or PBS. This effect of TGF-β1-exposed DC was associated with augmented spontaneous and AChR-induced proliferation, IFN-γ and NO production, and decreased levels of anti-AChR antibody-secreting cells. Autologous DC exposed in vitro to TGF-β1 could represent a new opportunity for DC-based immunotherapy of antibody-mediated autoimmune diseases. PMID:11876742

  6. The safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious uveitis in childhood.

    PubMed

    Little, Jessica A; Sen, Ethan S; Strike, Helen; Hinchcliffe, Annie; Guly, Catherine M; Lee, Richard W J; Dick, Andrew D; Ramanan, Athimalaipet V

    2014-01-01

    To assess the safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious childhood uveitis. Subjects were retrospectively selected from a database. Patients were included if they were diagnosed with chronic, noninfectious uveitis at 16 years of age or under and treated with triple immunosuppressive therapy for at least 6 months (following failure of a combination of 2 immunosuppressants). Patient demographics, diagnoses, duration of uveitis, drug dosages, active joint inflammation, and ophthalmologic data were recorded. Efficacy outcomes for triple therapy were recorded at 6 months. Thirteen patients with bilateral uveitis were included. Using Standardized Uveitis Nomenclature (SUN) criteria, at 6 months only 11 eyes (42%) had a 2-step improvement in anterior chamber cell inflammation (n = 26). In addition, 2 patients required additional oral corticosteroid treatment. There were 4 significant infectious adverse events during a total of 21.9 patient-years (PY) on triple therapy (0.18 events per PY). In this group of children with refractory uveitis, addition of a third immunosuppressive agent did not confer substantial benefit in redressing ocular inflammation and was associated with significant infections in a minority of patients.

  7. PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis.

    PubMed

    Carter, Laura L; Leach, Michael W; Azoitei, Mihai L; Cui, Junqing; Pelker, Jeffrey W; Jussif, Jason; Benoit, Steve; Ireland, Gretchen; Luxenberg, Deborah; Askew, G Roger; Milarski, Kim L; Groves, Christopher; Brown, Tom; Carito, Brenda A; Percival, Karen; Carreno, Beatriz M; Collins, Mary; Marusic, Suzana

    2007-01-01

    Interactions between PD-1 and its two differentially expressed ligands, PD-L1 and PD-L2, attenuate T cell activation and effector function. To determine the role of these molecules in autoimmune disease of the CNS, PD-1-/-, PD-L1-/- and PD-L2-/- mice were generated and immunized to induce experimental autoimmune encephalomyelitis (EAE). PD-1-/- and PD-L1-/- mice developed more severe EAE than wild type and PD-L2-/- mice. Consistent with this, PD-1-/- and PD-L1-/- cells produced elevated levels of the pro-inflammatory cytokines IFN-gamma, TNF, IL-6 and IL-17. These results demonstrate that interactions between PD-1/PD-L1, but not PD-1/PDL-2, are crucial in attenuating T cell responses in EAE.

  8. Loss of β-arrestin 2 exacerbates experimental autoimmune encephalomyelitis with reduced number of Foxp3+ CD4+ regulatory T cells

    PubMed Central

    Zhang, Yu; Liu, Chang; Wei, Bin; Pei, Gang

    2013-01-01

    β-Arrestins are well-known regulators and mediators of G protein-coupled receptor signalling, and accumulating evidence reveals that they are functionally involved in inflammation and autoimmune diseases. Of the two β-arrestins, β-arrestin 1 is documented to play regulatory roles in an animal model of multiple sclerosis (MS), whereas the role of β-arrestin 2 is less clear. Here, we show that β-arrestin 2-deficient mice displayed the exacerbated and sustained symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. At the cellular level, deficiency of β-arrestin 2 led to a decreased number of Foxp3+ CD4+ regulatory T (Treg) cells in peripheral lymphoid organs of EAE mice. Consistently, our in vitro observations also revealed that loss of β-arrestin 2 impaired the conversion of Foxp3− CD4+ T cells into Foxp3+ CD4+ inducible Treg cells. Taken together, our data suggest that β-arrestin 2 plays a regulatory role in MS, that is opposite to that of β-arrestin 1, in autoimmune diseases such as MS, which is at least partially through regulation of iTreg cell differentiation. PMID:23859136

  9. Effect of thalidomide and pentoxifylline on experimental autoimmune encephalomyelitis (EAE).

    PubMed

    Corrêa, José Otávio do Amaral; Aarestrup, Beatriz Julião Vieira; Aarestrup, Fernando Monteiro

    2010-11-01

    Autoimmune encephalomyelitis (EAE) in Lewis rats is a classical experimental model of demyelinating inflammatory disease of the central nervous system. EAE is widely accepted for study of immune-inflammatory mechanisms in the CNS related to multiple sclerosis (MS) due to similar clinical evolution. In the present study we investigated the effects of Thalidomide and pentoxifylline during EAE development in Lewis rats. EAE was induced in Lewis rats and treatment with Thalidomide or pentoxifylline was performed. Clinical evaluation was carried out daily. Histopathological analysis of the brain tissue and spinal cord was performed. Griess method was used for determination of NO serum levels. TNF-alpha and IFN-gamma serum levels were investigated using ELISA method. Thalidomide and pentoxifylline treatment is associated with significant reduction of neuroinflammation in CNS. Serum levels of NO, IFN-gamma and TNF-alpha showed a marked reduction. Such findings were correlated with improvement of clinical symptoms, particularly in thalidomide treated rats. Taken together the data suggested that thalidomide and pentoxifylline may be therapeutic options for the treatment of MS, however further experiments must be performed to investigate this hypothesis. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

    PubMed

    Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

    2013-12-01

    Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

  11. Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

    PubMed

    Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

    2016-04-01

    This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

  12. The frequency and outcome of uveitis in patients with newly diagnosed juvenile idiopathic arthritis in two 4-year cohorts from 1990-1993 and 2000-2003.

    PubMed

    Kotaniemi, Kaisu; Sihto-Kauppi, Kristiina; Salomaa, Pirjo; Säilä, Hanna; Ristolainen, Leena; Kauppi, Markku

    2014-01-01

    To retrospectively compare the frequency and outcome of uveitis between two cohorts of patients with newly-onset juvenile idiopathic arthritis (JIA) separated by a 10 year interval. The diagnosis of JIA was made in 239 patients in 1990-1993 and in 240 patients in 2000-2003 by paediatric rheumatologists at the Rheumatism Foundation Hospital, Heinola, Finland. An ophthalmologist examined all the patients regularly and diagnosed uveitis. The demographics of the patients, type of JIA, frequency, medical treatment and outcome of uveitis were documented. The main outcome measures were the frequency and outcome of uveitis, the number of complications and the best corrected visual acuity (BCVA), need of corticosteroids and other immunosuppressive treatment. The frequency of uveitis was higher (25% vs. 18%) in the earlier cohort. The visual outcome was ≥0.5 in all JIA-uveitis patients except one in the earlier cohort. Complications were fewer (21% vs. 35%) and uveitis was milder according to the Standardisation of Uveitis Nomenclature (SUN) criteria in the later cohort. Remission of uveitis (33% vs. 42%) and arthritis (20% vs. 23%) in JIA-uveitis patients was similar in both cohorts after a follow-up of 6.6 and 5.9 years, respectively. Systemic corticosteroids were more commonly used (25% vs. 7%) in JIA-uveitis patients of the earlier cohort but the use of methotrexate was equal in both cohorts (65% vs. 67%). In this study with early and aggressive treatment and close monitoring the outcome of JIA-uveitis patients was favourable and visual loss was avoided in most cases.

  13. Can infections prevent or cure allergy and autoimmunity?

    PubMed

    Kamradt, Thomas

    2005-06-01

    Extract: In western countries the prevalence and incidence of allergic and autoimmune diseases have been increasing dramatically over the last 50 years. In the last two decades, significant progress has been made towards understanding the genetic basis for susceptibility to autoimmunity or allergy. Genetic factors, however, cannot explain abrupt changes in disease incidence. It is therefore likely that environmental factors, specifically environmental factors that have changed over the last two generations, are critical for the increasing incidence of allergies and autoimmune diseases. Traditionally, autoimmune diseases such as multiple sclerosis (MS), type I diabetes, or rheumatoid arthritis (RA) are believed to have resulted from aberrant immune response to pathogens. In contrast, the "hygiene hypothesis," first postulated some 20 years ago, proposes that a lack of infections, especially during early childhood, predisposes one to the aberrant immune responses against harmless foreign antigens that cause allergic diseases such as rhinitis, atopic dermatitis, and allergic asthma. Several lines of epidemiological, clinical and experimental research point to more complex connections, either protective or pathogenic, between infection, allergy and autoimmunity.

  14. Tattoo-associated uveitis with or without systemic sarcoidosis: a comparative review of the literature.

    PubMed

    Kluger, N

    2018-05-15

    Sarcoidosis is a systemic disease of unknown aetiology characterized by the presence of non-caseating epithelioid cell granulomas in multiple organs, mainly the lungs and the lymphatic system. It is also one of the leading cause of inflammatory eye diseases. For the past 70 years, sarcoidal granulomas on tattoos and permanent make-up have been documented. They can be the first and sometimes unique cutaneous manifestation of systemic sarcoidosis. A few cases of sarcoidosis with uveitis and granulomatous reactions within tattoos have been described. However, since the end 60s, a singular entity has been reported associating isolated uveitis with granulomatous cutaneous reaction restricted to tattoos in the notable absence of systemic sarcoidosis. It remains unclear whether this entity must be distinguished from sarcoidosis. This review summarizes the currently available data on this topic and compares cases of sarcoidosis with granulomatous tattoo reaction and uveitis to the cases without notable sarcoidosis. We propose the acronym TAGU (TAttoo Granulomas with Uveitis) as an exclusion diagnosis that emcompasses the patients for whom we fail to find any sarcoidosis or other causes after extensive investigation. © 2018 European Academy of Dermatology and Venereology.

  15. Specialty Practice and Cost Considerations in the Management of Uveitis Associated With Juvenile Idiopathic Arthritis.

    PubMed

    Palestine, Alan G; Singh, Jasleen K; Kolfenbach, Jason R; Ozzello, Daniel J

    2016-07-01

    To evaluate whether cost, prior insurance authorization concerns, and subspecialty practice influence therapeutic decisions in the treatment of uveitis associated with juvenile idiopathic arthritis. A total of 2,965 pediatric ophthalmologists, uveitis specialists, retina specialists, and rheumatologists across the United States were surveyed via e-mail regarding their choice in long-term therapy for a hypothetical patient with uveitis associated with juvenile idiopathic arthritis. Outcomes of interest were differences in therapy choice based on cost/prior authorization and specialty practice. There were significant differences in the use of methotrexate and biologics among specialists, both with and without consideration for cost and prior authorization. Physicians in four different specialties who treat uveitis associated with juvenile idiopathic arthritis agree on methotrexate as a first-line treatment choice and a biologic immunosuppressive medication as a second choice, but there are significant differences between the specialties in their use of these medications. Cost and insurance considerations did not affect therapy selection. [J Pediatr Ophthalmol Strabismus. 2016;53(4):246-251.]. Copyright 2016, SLACK Incorporated.

  16. Characterization of amyloid in equine recurrent uveitis as AA amyloid.

    PubMed

    Ostevik, L; de Souza, G A; Wien, T N; Gunnes, G; Sørby, R

    2014-01-01

    Two horses with chronic uveitis and histological lesions consistent with equine recurrent uveitis (ERU) were examined. Microscopical findings in the ciliary body included deposits of amyloid lining the non-pigmented epithelium, intracytoplasmic, rod-shaped, eosinophilic inclusions and intraepithelial infiltration of T lymphocytes. Ultrastructural examination of the ciliary body of one horse confirmed the presence of abundant extracellular deposits of non-branching fibrils (9-11 nm in diameter) consistent with amyloid. Immunohistochemistry revealed strong positive labelling for AA amyloid and mass spectrometry showed the amyloid to consist primarily of serum amyloid A1 in both cases. The findings suggest that localized, intraocular AA amyloidosis may occur in horses with ERU. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Capsaicin-enriched diet ameliorates autoimmune neuritis in rats.

    PubMed

    Motte, Jeremias; Ambrosius, Björn; Grüter, Thomas; Bachir, Hussein; Sgodzai, Melissa; Pedreiturria, Xiomara; Pitarokoili, Kalliopi; Gold, Ralf

    2018-04-24

    Autoimmune neuropathies are common PNS disorders and effective treatment is challenging. Environmental influence and dietary components are known to affect the course of autoimmune diseases. Capsaicin as pungent component of chili-peppers is common in human nutrition. An influence of capsaicin on autoimmune diseases has been postulated. We tested capsaicin in the animal model of experimental autoimmune neuritis (EAN) in Lewis rat. Rats were immunized with P2-peptide and were treated with capsaicin in different preventive settings. Electrophysiological, histological, and molecular biological analyses of the sciatic nerve were performed to analyze T-cell and macrophage cell count, TRPV1, and cytokine expression. Moreover, FACS analyses including the intestinal immune system were executed. We observed an immunomodulatory effect of an early preventive diet-concept, where a physiological dosage of oral capsaicin was given 10 days before immunization in EAN. A reduced inflammation of the sciatic nerve was significant detectable clinically, electrophysiologically (CMAPs reduced in control group p < 0.01; increase of nerve conduction blocks in control group p < 0.05), histologically (significant reduction of T-cells, macrophages and demyelination), and at cytokine level. In contrast, this therapeutic effect was missing with capsaicin given from the day of immunization onwards. As possible underlying mechanism, we were able to show changes in the expression of the capsaicin receptor in the sciatic nerve and the small intestine, as well as altered immune cell populations in the small intestine. This is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies.

  18. Galectin-3 in autoimmunity and autoimmune diseases

    PubMed Central

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo

    2015-01-01

    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell–cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte–macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID:26142116

  19. Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling

    PubMed Central

    Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido

    2015-01-01

    Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune

  20. Neuroaxonal ion dyshomeostasis of the normal-appearing corpus callosum in experimental autoimmune encephalomyelitis.

    PubMed

    Chen, Chiao-Chi V; Zechariah, Anil; Hsu, Yi-Hua; Chen, Hsiao-Wen; Yang, Li-Chuan; Chang, Chen

    2008-04-01

    Atrophy of the corpus callosum (CC) is a well-documented observation in clinically definite multiple sclerosis (MS) patients. One recent hypothesis for the neurodegeneration that occurs in MS is that ion dyshomeostasis leads to neuroaxonal damage. To examine whether ion dyshomeostasis occurs in the CC during MS onset, experimental autoimmune encephalomyelitis (EAE) was utilized as an animal MS model to induce autoimmunity-mediated responses. To date, in vivo investigations of neuronal ion homeostasis has not been feasible using traditional neuroscience techniques. Therefore, the current study employed an emerging MRI method, called Mn2+-enhanced MRI (MEMRI). Mn2+ dynamics is closely associated with important neuronal activity events, and is also considered to be a Ca2+ surrogate. Furthermore, when injected intracranially, Mn2+ can be used as a multisynaptic tracer. These features enable MEMRI to detect neuronal ion homeostasis within a multisynaptic circuit that is connected to the injection site. Mn2+ was injected into the visual cortex to trace the CC, and T1-weighted imaging was utilized to observe temporal changes in Mn2+-induced signals in the traced pathways. The results showed that neuroaxonal functional changes associated with ion dyshomeostasis occurred in the CC during an acute EAE attack. In addition, the pathway appeared normal, although EAE-induced immune-cell infiltration was visible around the CC. The findings suggest that ion dyshomeostasis is a major neuronal aberration underlying the deterioration of normal-appearing brain tissues in MS, supporting its involvement in neuroaxonal functioning in MS.

  1. Myeloid-derived suppressor cells as a potential therapy for experimental autoimmune myasthenia gravis

    PubMed Central

    Li, Yan; Tu, Zhidan; Qian, Shiguang; Fung, John J.; Markowitz, Sanford D.; Kusner, Linda L.; Kaminski, Henry J.; Lu, Lina; Lin, Feng

    2016-01-01

    We recently demonstrated that hepatic stellate cells induce the differentiation of myeloid-derived suppressor cells (MDSCs) from myeloid progenitors. In this study, we found that adoptive transfer of these MDSCs effectively reversed disease progression in experimental autoimmune myasthenia gravis (EAMG), a T-cell-dependent and B-cell-mediated model for myasthenia gravis. In addition to ameliorated disease severity, MDSC-treated EAMG mice showed suppressed acetylcholine receptors (AChR)-specific T-cell responses, decreased levels of serum anti-AChR IgGs, and reduced complement activation at the neuromuscular junctions. Incubating MDSCs with B cells activated by anti-IgM or anti-CD40 antibodies inhibited the proliferation of these in vitro activated B cells. Administering MDSCs into mice immunized with a T-cell-independent antigen inhibited the antigen-specific antibody production in vivo. MDSCs directly inhibit B cells through multiple mechanisms including prostaglandin E2, inducible nitric oxide synthase and arginase. Interestingly, MDSC treatment in EMAG mice does not appear to significantly inhibit their immune response to a non-relevant antigen, ovalbumin. These results demonstrated that hepatic stellate cell-induced MDSCs concurrently suppress both T- and B- cell autoimmunity, leading to effective treatment of established EAMG; and that the MDSCs inhibit AChR-specific immune responses at least partially in an antigen-specific manner. These data suggest that MDSCs could be further developed as a novel approach to treating myasthenia gravis and, even more broadly, other diseases in which T and B cells are involved in pathogenesis. PMID:25057008

  2. Myeloid-derived suppressor cells as a potential therapy for experimental autoimmune myasthenia gravis.

    PubMed

    Li, Yan; Tu, Zhidan; Qian, Shiguang; Fung, John J; Markowitz, Sanford D; Kusner, Linda L; Kaminski, Henry J; Lu, Lina; Lin, Feng

    2014-09-01

    We recently demonstrated that hepatic stellate cells induce the differentiation of myeloid-derived suppressor cells (MDSCs) from myeloid progenitors. In this study, we found that adoptive transfer of these MDSCs effectively reversed disease progression in experimental autoimmune myasthenia gravis (EAMG), a T cell-dependent and B cell-mediated model for myasthenia gravis. In addition to ameliorated disease severity, MDSC-treated EAMG mice showed suppressed acetylcholine receptor (AChR)-specific T cell responses, decreased levels of serum anti-AChR IgGs, and reduced complement activation at the neuromuscular junctions. Incubating MDSCs with B cells activated by anti-IgM or anti-CD40 Abs inhibited the proliferation of these in vitro-activated B cells. Administering MDSCs into mice immunized with a T cell-independent Ag inhibited the Ag-specific Ab production in vivo. MDSCs directly inhibit B cells through multiple mechanisms, including PGE2, inducible NO synthase, and arginase. Interestingly, MDSC treatment in EAMG mice does not appear to significantly inhibit their immune response to a nonrelevant Ag, OVA. These results demonstrated that hepatic stellate cell-induced MDSCs concurrently suppress both T and B cell autoimmunity, leading to effective treatment of established EAMG, and that the MDSCs inhibit AChR-specific immune responses at least partially in an Ag-specific manner. These data suggest that MDSCs could be further developed as a novel approach to treating myasthenia gravis and, even more broadly, other diseases in which T and B cells are involved in pathogenesis. Copyright © 2014 by The American Association of Immunologists, Inc.

  3. Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

    PubMed

    Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

    2017-07-01

    The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

  4. Update on the Treatment of Uveitis in Patients with Juvenile Idiopathic Arthritis: A Review.

    PubMed

    Asproudis, Ioannis; Katsanos, Andreas; Kozeis, Nikolaos; Tantou, Alexandra; Konstas, Anastasios G

    2017-12-01

    Chronic uveitis is a common extra-articular manifestation of juvenile idiopathic arthritis. The classic clinical picture is one of chronic anterior uveitis, which usually remains asymptomatic until ocular complications arise. The risk of uveitis is increased in girls with an early onset of oligoarthritis and positive antinuclear antibodies. Even though the inflammation in patients with juvenile idiopathic arthritis is initially limited in the anterior part of the eye, chronic active inflammation may eventually cause significant damage to the posterior pole. Complications may include band keratopathy, cataract, secondary glaucoma, posterior synechiae, cystoid macular edema, and hypotony. The cooperation of ophthalmologists with rheumatologists may help define the best treatment plan. The ophthalmic therapeutic regimen includes topical corticosteroids and mydriatics, while in severe cases immunosuppressive and biological agents are introduced. Surgical management of complications might be needed.

  5. Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis.

    PubMed

    Koch, Marcus W; Zabad, Rana; Giuliani, Fabrizio; Hader, Walter; Lewkonia, Ray; Metz, Luanne; Wee Yong, V

    2015-11-15

    Microglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo. We activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology. HCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals. HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Chest Radiographic Screening for Sarcoidosis in the Diagnosis of Patients with Active Uveitis.

    PubMed

    Groen, Fahriye; van Laar, Jan A M; Rothova, Aniki

    2017-06-01

    Although chest radiography is currently recommended for the initial evaluation of patients with new-onset uveitis, the efficacy of this diagnostic screening modality is not known. To evaluate the diagnostic value of chest radiographs in patients with active uveitis of recent onset in a tertiary center in Western Europe. A retrospective cross-sectional study was conducted by reviewing all chest imaging for adults with new-onset (<1 yr) uveitis of unknown origin undergoing initial evaluation in the Department of Ophthalmology at Erasmus University Medical Center (Rotterdam, the Netherlands). Radiographic findings were related to clinical and other imaging characteristics and to final diagnoses. Screening chest radiographs were abnormal for 30 of 200 patients (15%) included in this study. Twenty-two of the 200 patients (11%) had biopsy-confirmed sarcoidosis, and an additional 12 patients were presumed to have sarcoidosis. The finding of chest radiographic abnormalities interpreted as typical of sarcoidosis was specific (91%; 95% confidence interval, 85.9-94.4%) but not sensitive (64%; 95% confidence interval, 43.0-80.3%) for biopsy-confirmed sarcoidosis. The combination of elevated serum angiotensin-converting enzyme level and chest radiographic findings typical of sarcoidosis increased the sensitivity to 79%. Biopsy-confirmed sarcoidosis was more common in patients with panuveitis (17 of 84; 20%) compared to patients with other anatomical locations of uveitis (5 of 116, 4%; P < 0.001). One patient was diagnosed with active pulmonary and ocular tuberculosis. Abnormal chest radiographs were found in 15% of patients with active uveitis of unknown origin and onset within 1 year of referral to a tertiary center in the Netherlands. A majority of the abnormal chest radiographs showed findings compatible with a diagnosis of sarcoidosis.

  7. Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis.

    PubMed

    Miyamoto, Katsuichi; Tanaka, Noriko; Moriguchi, Kota; Ueno, Rino; Kadomatsu, Kenji; Kitagawa, Hiroshi; Kusunoki, Susumu

    2014-05-01

    Chondroitin sulfate proteoglycans (CSPGs) are the main component of the extracellular matrix in the central nervous system (CNS) and influence neuroplasticity. Although CSPG is considered an inhibitory factor for nerve repair in spinal cord injury, it is unclear whether CSPG influences the pathogenetic mechanisms of neuroimmunological diseases. We induced experimental autoimmune encephalomyelitis (EAE) in chondroitin 6-O-sulfate transferase 1-deficient (C6st1(-/-)) mice. C6ST1 is the enzyme that transfers sulfate residues to position 6 of N-acetylgalactosamine in the sugar chain of CSPG. The phenotypes of EAE in C6st1(-/-) mice were more severe than those in wild-type (WT) mice were. In adoptive-transfer EAE, in which antigen-reactive T cells from WT mice were transferred to C6st1(-/-) and WT mice, phenotypes were significantly more severe in C6st1(-/-) than in WT mice. The recall response of antigen-reactive T cells was not significantly different among the groups. Furthermore, the number of pathogenic T cells within the CNS was also not considerably different. When EAE was induced in C6ST1 transgenic mice with C6ST1 overexpression, the mice showed considerably milder symptoms compared with those in WT mice. In conclusion, the presence of sulfate at position 6 of N-acetylgalactosamine of CSPG may influence the effecter phase of EAE to prevent the progression of pathogenesis. Thus, modification of the carbohydrate residue of CSPG may be a novel therapeutic strategy for neuroimmunological diseases such as multiple sclerosis.

  8. Adalimumab for treatment of severe Behçet's uveitis: a retrospective long-term follow-up study.

    PubMed

    Interlandi, Emanuela; Leccese, Pietro; Olivieri, Ignazio; Latanza, Loredana

    2014-01-01

    Behçet's disease (BD) is a chronic multisystem inflammatory disorder associated to uveitis that may represent a serious sight-threatening condition. The purpose of the present study is to assess the effectiveness of adalimumab as new strategic therapeutic approach in patients affected by severe Behçet's uveitis. Clinical data from twelve selected patients (22 eyes) were retrospectively analysed. All patients received 40 mg of adalimumab subcutaneously, once every 2 weeks, in addition to traditional immunosuppressive on-going therapy and eight of them were switched to adalimumab after failure of infliximab therapy. Primary outcome measures included ocular inflammatory activity, frequency of uveitis attacks and steroid-sparing effect. Secondary outcomes were changes of best-corrected visual acuity (BCVA), impact on traditional immunosuppressive therapy and occurrence of adalimumab-related side effects. Mean age of patients (11 males and 1 female) at the onset of disease was 24.34 years (±8.62 SD). Ocular involvement resulted bilateral in 83% of cases and mainly consisted in panuveitis (68% of eyes). After mean follow-up of 21 months (±9.63 SD) all patients but one (92%) achieved uveitis remission with BCVA improvement at least in one eye. Average uveitis attacks decreased from 2 to 0,42 during adalimumab (p<0.001) and daily-steroid dose was tapered in all adalimumab responders up to suspension in seven of them. No patient developed related side effects during adalimumab administration. Our results demonstrate that adalimumab is a very effective and safe option for treatment of patients with severe and resistant Behçet's uveitis, providing an appropriate and long-term control of ocular inflammation.

  9. Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

    PubMed Central

    Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Hask’, György; ’iháková, Daniela; Mechoulam, Raphael; Pacher, Pal

    2016-01-01

    Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. PMID:26772776

  10. Bilateral nongranulomatous uveitis with infective endocarditis.

    PubMed

    Ha, Sang Won; Shin, Jae Pil; Kim, Si Yeol; Park, Dong Ho

    2013-02-01

    A 32-year-old male who had infective endocarditis complained of photophobia and blurred vision in both eyes. Biomicroscopic examination and fundus examination revealed anterior chamber reaction, vitritis, optic disc swelling, and Roth spots. He was diagnosed with bilateral nongranulomatous uveitis and treated with topical steroid eye drops and posterior sub-Tenon injection of triamcinolone. His visual symptoms were resolved within 1 week, and inflammation resolved within 4 weeks after treatment.

  11. Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

    PubMed

    Joshi, Lavnish; Talat, Lazha; Yaganti, Satish; Sandhu, Sartaj; Taylor, Simon R J; Wakefield, Denis; McCluskey, Peter; Lightman, Susan

    2014-05-01

    To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. Retrospective cohort study. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. Our data suggest that control of inflammation can be achieved after switching or combining ISAs. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  12. The Autoimmune Ecology

    PubMed Central

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A.; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures – internal and external – across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied. PMID:27199979

  13. The Autoimmune Ecology.

    PubMed

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  14. Long-term outcome after implantation of a suprachoroidal cyclosporine drug delivery device in horses with recurrent uveitis.

    PubMed

    Gilger, Brian C; Wilkie, David A; Clode, Allison B; McMullen, Richard J; Utter, Mary E; Komaromy, Andras M; Brooks, Dennis E; Salmon, Jacklin H

    2010-09-01

    To determine the long-term efficacy, complications, and duration of effect of a cyclosporine (CsA) suprachoroidal implant (CSI) in horses with equine recurrent uveitis (ERU). Horses with ERU were treated with a 6-mm diameter, 25 mg, reservoir matrix CsA implant in the deep sclera adjacent to the suprachoroidal space. Horses with follow-up >1 year were examined for frequency of uveitis episodes, complications, and vision at last recheck. Data from 151 eyes of 133 horses from the USA and Europe that had CsA devices implanted for ERU were reviewed. Follow-up time ranged from 13 to 85 months after surgery, with a mean and median follow-up time of 28.9 and 26.3 months, respectively. Overall, at last follow-up 78.8% of eyes were considered visual and the overall mean frequency of uveitis episodes after CSI was 0.09 ± SD 0.08 episodes per month. The most common complications leading to vision loss at last follow-up were persistent uveitis episodes (54%), glaucoma (22%), mature cataracts (16%), and retinal detachment (6%). Persistent uveitis episodes tended to be the highest cause of vision loss in horses with <24 months and >48 months of follow-up. This study demonstrated the long-term maintenance of vision of horses with ERU implanted with a CSI. The increased vision loss related to uveitis episode of inflammation in eyes after the likely depletion of CsA from the CSI suggests that a repeat CSI may be required at or before 48 months after surgery.

  15. Effect of vaccination against leptospirosis on the frequency, days to recurrence and progression of disease in horses with equine recurrent uveitis.

    PubMed

    Rohrbach, Barton W; Ward, Daniel A; Hendrix, Diane V H; Cawrse-Foss, Margaret; Moyers, Tammy D

    2005-01-01

    To evaluate the effect of vaccination against leptospirosis on frequency and days to recurrence of uveitis and progression of disease in horses with equine recurrent uveitis (ERU). Forty-one horses with ERU. Horses were randomly assigned to experimental (vaccinated) or control groups. Vaccine containing six serovars of Leptospira or placebo was administered, an ophthalmic examination performed and blood samples drawn on days 0, 28, 180 and 365. Antibody titers were measured against each serovar. Recurrence of uveitis was verified by ophthalmic examination. Results of the initial and final ophthalmic examinations were compared and progression of disease defined as an increase in extent of synechiae, or development of new or progression of an existing cataract. Vaccination increased the average geometric mean serum antibody titer from 225 on day 0, to 4077 and 593 on days 28 and 180, respectively. After the second vaccination, days to first recurrence was significantly longer (median 126 days; range 24-231 days) when compared with controls (median 86 days; range 14-192 days, P=0.04). Recurrence of ERU was observed among 7/20 (35%) vaccinated horses and 12/21 (57%) controls; however, this difference was not statistically significant (P=0.061, OR 0.25, 95% CI 0.06, 1.07). More horses in the experimental group 13/20 (65%) experienced progression of disease when compared with controls 12/21(57%); however, this difference was statistically nonsignificant (P=0.35). Vaccine significantly increased days to recurrence, but failed to slow the progression of disease. These data do not support the use of vaccination against leptospirosis as adjunct therapy for the routine treatment of horses with ERU.

  16. Avian models with spontaneous autoimmune diseases

    PubMed Central

    Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

    2012-01-01

    Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

  17. [Combination surgery for wet age-related macular degeneration and chronic peripheral uveitis].

    PubMed

    Zapuskalov, I V; Krivosheina, O I; Khoroshikh, Yu I

    2016-01-01

    To develop a combination surgery for wet age-related macular degeneration and concurrent chronic peripheral uveitis that would include intravitreal injection of Lucentis and cryocerclage of the peripheral retina. A total of 75 patients were examined and divided into 2 groups: the main group (37 patients) and the controls (38 patients). Patients from the main group underwent the new combination surgery, while the controls received intravitreal Lucentis alone (peripheral uveitis was managed therapeutically). It has been found that the new combination method provides a significant and stable improvement in visual acuity (by a factor of 10) and a decrease in the area of central scotoma (by a factor of 2.95) in the postoperative period. The period needed for recovery in the central retinal thickness is also 1.6 times shorter. The new combination surgery for wet age-related macular degeneration and concurrent chronic peripheral uveitis provides rapid reduction of inflammation in the extreme periphery of the fundus and a 1.5 times faster (as compared to traditional methods) primary restoration of topographic anatomy of the retina in the macular region.

  18. Vaccination and autoimmunity-'vaccinosis': a dangerous liaison?

    PubMed

    Shoenfeld, Y; Aron-Maor, A

    2000-02-01

    The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed. Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome). The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this

  19. Indocyanine green angiography in patients with human T cell-lymphotropic virus type 1 uveitis.

    PubMed

    Sakurai, Toshiya; Yukawa, Eiichi; Hara, Yoshiaki; Miyata, Norio; Mochizuki, Manabu

    2002-02-01

    To determine the indocyanine green (ICG) angiographic features and to evaluate the choroidal involvement of human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis. We performed ICG angiography using scanning laser ophthalmoscopy in 54 eyes of 27 patients (8 men and 19 women) diagnosed with HTLV-1 uveitis. The patient's mean age was 51.5 years with a range of 24-65 years. The early phase of ICG angiography revealed ICG leakage from the choroidal vessels in the posterior pole, hyperfluorescent spots that which were not detected with fluorescein angiography, and small hypofluorescent lesions in the macula which most likely corresponded to microcirculatory disturbances in the choriocapillaris. We suggest that the ICG angiographic findings reflect choroidal lesions such as infiltration with leukocytes and edema. ICG angiography may provide useful information on choroidopathy in HTLV-1 uveitis.

  20. Scintigraphy of sacroliac joints in acute anterior uveitis. A study of thirty patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Russell, A.S.; Lentle, B.C.; Percy, J.S.

    1976-11-01

    HLA-B27 is a transplantation antigen found in a high proportion of patients with ankylosing spondylitis. Recently, an association has been shown to exist between HLA-B27 and acute uveitis, even in the absence of ankylosing spondylitis. We have examined the HLA antigen profile of 45 patients with acute nongranulomatous anterior uveitis and have confirmed this relation. In addition, using 90m technetium stannous pyrophosphate we have been able to demonstrate abnormal bone scan in 19 of 30 patients studied. Such abnormalities are limited to the sacroiliac joints but are otherwise the same as those seen in overt ankylosing spondylitis. Seven of themore » 19 patients did not have HLA-B27. These factors suggest that acute anterior uveitis may often represent a manifestation of a spondylitic diathesis even in the complete absence of any suggestive symptomatic or radiologic change and, in some cases, even through the antigenic marker HLA-B27 may be absent.« less

  1. Scintigraphy of sacroiliac joints in acute anterior uveitis. A study of thirty patients.

    PubMed

    Russell, A S; Lentle, B C; Percy, J S; Jackson, F I

    1976-11-01

    HLA-B27 is a transplantation antigen found in a high proportion of patients with ankylosing spondylitis. Recently, an association has been shown to exist between HLA-B27 and acute uveitis, even in the absence of ankylosing spondylitis. We have examined the HLA antigen profile of 45 patients with acute nongranulomatous anterior uveitis and have confirmed this relation. In addition, using 90mtechnetium stannous pyrophosphate we have been able to demonstrate abnormal bone scan in 19 of 30 patients studied. Such abnormalities are limited to the sacroiliac joints but are otherwise the same as those seen in overt ankylosing spondylitis. Seven of the 19 patients did not have HLA-B27. These factors suggest that acute anterior uveitis may often represent a manifestation of a spondylitic diathesis even in the complete absence of any suggestive symptomatic or radiologic change and, in some cases, even though the antigenic marker HLA-B27 may be absent.

  2. Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment

    PubMed Central

    Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

    2015-01-01

    The aim of this study was to quantify the proportion of regulatory T cells (Treg) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)+ Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4+ T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3+ Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3+ Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3+ Treg cells. PMID:25354724

  3. Uveitis induction in the rabbit by muramyl dipeptides.

    PubMed Central

    Waters, R V; Terrell, T G; Jones, G H

    1986-01-01

    Intraocular inflammation (uveitis) was produced in rabbits by intravenous or subcutaneous treatment with N-acetylmuramyl-L-alanyl-D-isoglutamine and several of its synthetic analogs at doses of greater than or equal to 0.2 mg/kg in saline. A dose-dependent increase in permeability of the ocular blood-aqueous barrier as measured by leakage of protein or fluoresceinated dextran from the serum into the eye was observed from 2 to 14 h after glycopeptide treatment. Peak response occurred at approximately 3 h postdose. The lowest dose found to produce maximal vascular leakage for the most active glycopeptide analogs was 1 mg/kg. The adjuvant-inactive L-L stereoisomer of N-acetylmuramyl-L-alanyl-D-isoglutamine was inactive, even at doses as high as 10 mg/kg. Analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine which were homologous in the lactyl side chain were found to cause less uveitis. Chronic biweekly intravenous treatment of rabbits for 1 month with either N-acetyl-L-alpha-aminobutyryl-D-isoglutamine or its lipophilic 6-O-stearoyl derivative at 1 mg/kg, but not with murabutide, resulted in leukocytic inflammatory lesions unique to the uveal tract of the eye. The uveitis was potentially reversible and occurred with decreased severity as long as 2 months after cessation of chronic treatment. Vascular leakage but not cellular infiltrate in the choroid could be modulated by pharmacologic means. Pyrogenicity but not adjuvanticity correlated with ability of glycopeptides to induce vascular leakage. Several adjuvant-active muramyl dipeptide analogs with minimal ability to cause acute vascular leakage or chronic inflammation in the rabbit eye have been identified. Images PMID:3949381

  4. The Risk of Intraocular Pressure Elevation in Pediatric Non-infectious Uveitis

    PubMed Central

    Kothari, Srishti; Foster, C. Stephen; Pistilli, Maxwell; Liesegang, Teresa L.; Daniel, Ebenezer; Sen, H. Nida; Suhler, Eric B.; Thorne, Jennifer E.; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Lawrence, Scott D.; Kempen, John H.

    2015-01-01

    Purpose To characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric non-infectious uveitis. Design Multi-center retrospective cohort study. Participants Nine hundred sixteen children (1593 eyes) <18 years old at presentation with non-infectious uveitis followed between January 1978 through December 2007 at five academic uveitis centers in United States. Methods Medical records review by trained, certified experts. Main outcome measures Prevalence and incidence of IOP≥21 and ≥30mmHg and incidence of a rise in IOP by ≥10mmHg. To avoid under ascertainment, outcomes were counted as present when IOP-lowering therapies were in use. Results Initially 251 (15.8%) and 46 eyes (2.9%) had IOP≥21 and ≥30mmHg, respectively. Factors associated with presenting IOP elevation included age 6–12 years (versus other pediatric ages), prior cataract surgery (adjusted odds ratio≥21mmHg [aOR21]=2.42, P=0.01), pars plana vitrectomy (adjusted odds ratio≥30mmHg[aOR30]=11.1, P=0.03), duration of uveitis ≥6 months (aORs30 up to 11.8, P<0.001), contralateral IOP elevation (aOR21=16.9, aOR30=8.29; each P<0.001), visual acuity worse than 20/40 (aORs21 up to 1.73, P=0.02; aORs30 up to 2.81 P=0.03), and topical corticosteroid use (aORs up to 8.92, P<0.001 in a dose-response relationship). The median follow-up was 1.25 years (interquartile range 0.4–3.66). The estimated risk of any observed IOP elevation to ≥21 mmHg, ≥30 mmHg and of a rise in IOP by ≥10mmHg was 33.4%, 14.8% and 24.4% respectively within 2 years. Factors associated with IOP elevation included pars plana vitrectomy (adjusted hazard ratio≥21mmHg[aHR21]=3.36, P<0.001), contralateral IOP elevation (aHRs up to 9.54, P<0.001), the use of topical (aHRs up to 8.77 that followed a dose-response relationship, P<0.001), periocular (aHRs up to 7.96, P<0.001) and intraocular (aHRs up to 19.7, P<0.001) corticosteroids. Conclusions IOP elevation affects a large minority of children

  5. Bilateral Nongranulomatous Uveitis with Infective Endocarditis

    PubMed Central

    Ha, Sang Won; Shin, Jae Pil; Kim, Si Yeol

    2013-01-01

    A 32-year-old male who had infective endocarditis complained of photophobia and blurred vision in both eyes. Biomicroscopic examination and fundus examination revealed anterior chamber reaction, vitritis, optic disc swelling, and Roth spots. He was diagnosed with bilateral nongranulomatous uveitis and treated with topical steroid eye drops and posterior sub-Tenon injection of triamcinolone. His visual symptoms were resolved within 1 week, and inflammation resolved within 4 weeks after treatment. PMID:23372383

  6. Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment.

    PubMed

    Peón, Alberto N; Ledesma-Soto, Yadira; Olguín, Jonadab E; Bautista-Donis, Marcel; Sciutto, Edda; Terrazas, Luis I

    2017-01-01

    A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis (MS). The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES) that may suppress EAE development were sought for. Interestingly, it was discovered that TcES was able to suppress EAE development with more potency than dexamethasone; moreover, TcES treatment was still effective even when inoculated at later stages after the onset of EAE. Importantly, the TcES treatment was able to induce a range of Th2-type cytokines, while suppressing Th1 and Th17 responses. Both the polyclonal and the antigen-specific proliferative responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in association with a potent recruitment of suppressor cell populations. Peritoneal inoculation of TcES was able to direct the normal inflammatory cell traffic to the site of injection, thus modulating CNS infiltration, which may work along with Th2 immune polarization and lymphocyte activation impairment to downregulate EAE development.

  7. Use of methotrexate in patients with uveitis.

    PubMed

    Ali, A; Rosenbaum, J T

    2010-01-01

    Methotrexate has been frequently employed to treat ocular inflammatory diseases including uveitis, scleritis, and orbital inflammatory disease. It is effective for intraocular lymphoma when given directly into the eye. No study has assessed its efficacy for eye disease in a randomised, placebo controlled design. This report reviews the literature relevant to methotrexate's utility in the treatment of ocular inflammatory disease.

  8. PERIOCULAR CORTICOSTEROID INJECTIONS IN UVEITIS: EFFECTS AND COMPLICATIONS

    PubMed Central

    Sen, H. Nida; Vitale, Susan; Gangaputra, Sapna S.; Nussenblatt, Robert B.; Liesegang, Teresa L.; Levy-Clarke, Grace A.; Rosenbaum, James T.; Suhler, Eric B.; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Kempen, John H.

    2014-01-01

    Purpose To evaluate the benefits and complications of periocular depot corticosteroid injections in patients with ocular inflammatory disorders. Design Multicenter retrospective cohort study. Participants A total of 914 patients (1192 eyes) who had received at least one periocular corticosteroid injection at 5 tertiary uveitis clinics in the United States. Methods Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Demographic and clinical characteristics were obtained at every visit via medical record review by trained reviewers. Main Outcome Measures Control of inflammation, improvement of visual acuity to 20/40 or better, improvement of visual acuity loss attributed to macular edema, incident cataract affecting visual acuity, cataract surgery, ocular hypertension and glaucoma surgery. Results Among 914 patients (1192 eyes) who received at least one periocular injection during follow-up, 286 (31.3%) were classified as having anterior uveitis, 303 (33.3%) as intermediate uveitis, 324 (35.4%) as posterior or panuveitis. Cumulatively by ≤6 months, 72.7% [95% confidence interval (95%CI): 69.1-76.3] of the eyes achieved complete control of inflammation and 49.7% [95%CI:45.5-54.1] showed an improvement in visual acuity (VA) from worse than 20/40 to 20/40 or better. Among the subset with VA worse than 20/40 attributed to macular edema, 33.1% [95%CI: 25.2-42.7] improved to 20/40 or better. By 12 months, the cumulative incidence of one or more visits with an intraocular pressure≥24 mmHg and ≥30 mmHg was 34.0% [95%CI: 24.8-45.4] and 15.0% [95%CI: 11.8-19.1] respectively; glaucoma surgery was performed in 2.4% [95%CI: 1.4-3.9] of eyes. Within 12 months, among phakic eyes initially 20/40 or better, the incidence of a reduction in VA to worse than 20/40 attributed to cataract was 20.2% [95%CI: 15.9-25.6]; cataract surgery was performed within 12 months in 13.8 % [95%CI: 11.1-17.2] of the initially phakic eyes

  9. A Comprehensive Review of mTOR-Inhibiting Pharmacotherapy for the Treatment of Non-Infectious Uveitis.

    PubMed

    Blair, Joshua; Barry, Robert; Moore, David J; Denniston, Alastair K

    2017-01-01

    Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role. A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious uveitis was performed. Articles were identified by a search of MEDLINE (PubMed/OVID) and EMBASE (OVID) the terms (uveitis OR non-infectious uveitis) AND (mTOR inhibitor OR sirolimus OR everolimus). Assessment of study aims, methods, efficacy outcomes and adverse events was performed. Seven pre-clinical and nine clinical studies were identified. One study in each group was on everolimus, the rest sirolimus. Preclinical studies have been performed in rabbit, rat, mouse and in-vitro models. Clinical studies range from comparative open-label trials to case reports, with reported clinical efficacy ranging from 40% to 100% depending on endpoint assessed. The overall rate of drug-related adverse events (such as ocular irritation, visual floaters, nausea and vomiting) was 0.640 events per patient-year with sirolimus, and 0.111 events per patient-year with everolimus. Published evidence suggests that sirolimus and everolimus may be useful in the management of noninfectious uveitis. Both appear to be well tolerated, especially when locally administered. Further high-quality RCTs adopting standardised end-points are required to definitively determine the efficacy of each agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Anterior uveitis as a complication of treatment with high dose cytosine-arabinoside.

    PubMed

    Planer, David; Cukierman, Tali; Liebster, Diana; Ilsar, Michael; Chajek-Shaul, Tova

    2004-07-01

    We present a case of a 21-year-old woman suffering from diffuse large B-cell lymphoma who developed acute anterior uveitis shortly after completing chemotherapeutic course with HYPER-CVAD protocol (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) alternating with methotrexate and high-dose cytosine-arabinoside (HIDAC), with poor adherence to recommended prophylactic treatment with saline eye drops. Complete resolution of her symptoms was achieved within a few days of treatment with topical steroids. To our knowledge this is the first report of acute anterior uveitis secondary to treatment with HIDAC. Differential diagnosis and a suggested mechanism are discussed. Copyright 2004 Wiley-Liss, Inc.

  11. Measuring visual outcomes in children with uveitis using the “Effects of Youngsters’ Eyesight on Quality of Life” questionnaire

    PubMed Central

    Angeles-Han, Sheila T.; Yeh, Steven; McCracken, Courtney; Jenkins, Kirsten; Stryker, Daneka; Myoung, Erica; Vogler, Larry; Rouster-Stevens, Kelly; Lambert, Scott R.; Harrison, Melanie J.; Prahalad, Sampath; Drews-Botsch, Carolyn

    2015-01-01

    Objective The Effects of Youngsters’ Eyesight on Quality of Life (EYE-Q) is a novel measure of vision-related quality of life (QOL) and function in children. We aim to determine the validity of EYE-Q in childhood uveitis. Methods We abstracted medical record data on arthritis and uveitis in a convenience sample of children with juvenile idiopathic arthritis (JIA) and/or uveitis. In addition to the EYE-Q, parents and patients completed questionnaires on overall QOL (Pediatric QOL Inventory - PedsQL), and physical functioning (Childhood Health Assessment Questionnaire - CHAQ). Results Among 57 children (8 JIA, 24 JIA and uveitis, 25 uveitis alone), 102 ocular examinations were performed within 1 month of completing questionnaires. Uveitis patients had bilateral disease (69%), anterior involvement (78%), synechiae (51%) and cataracts (49%). Children with vision loss in their better eye (visual acuity (VA) 20/50 or worse) had worse EYE-Q (p = 0.006), and PedsQL (p = 0.028), but not CHAQ scores. The EYE-Q moderately correlated with logMAR VA (rs = −0.43), PedsQL (rs = 0.43) and CHAQ (rs = −0.45), but was not correlated with anterior chamber cells or intraocular pressure. The PedsQL and CHAQ did not correlate with VA or cells. There were strong correlations between the parent and child EYE-Q (rs = 0.62). Cronbach's α for the child report was 0.91. The EYE-Q had strong test-retest reliability (rs=0.75). Conclusion The EYE-Q may be an important tool in the assessment of visual outcomes in childhood uveitis and an improvement over general measures in detecting changes in vision-related function. PMID:26037544

  12. Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection.

    PubMed

    Einstein, Ofira; Fainstein, Nina; Touloumi, Olga; Lagoudaki, Roza; Hanya, Ester; Grigoriadis, Nikolaos; Katz, Abram; Ben-Hur, Tamir

    2018-01-01

    Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized. To assess effects of ET on systemic autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. To assess direct neuroprotective effects of ET, PLP-reactive LN-T cells were transferred into recipient mice that were trained prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and the characteristics of encephalitogenic LN-T cells derived from PLP-immunized mice were evaluated in vitro. LN-T cells obtained from trained mice induced an attenuated clinical and pathological EAE in recipient mice vs. cells derived from sedentary animals. Training inhibited the activation, proliferation and cytokine gene expression of PLP-reactive T cells in response to CNS-derived autoantigen, but strongly enhanced their proliferation in response to Concanavalin A, a non-specific stimulus. However, there was no difference in EAE severity when autoreactive encephalitogenic T cells were transferred to trained vs. sedentary recipient mice. ET inhibits immune system responses to an auto-antigen to attenuate EAE, rather than generally suppressing the immune system, but does not induce a direct neuro-protective effect against EAE. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. A human anti-neuronal autoantibody against GABA B receptor induces experimental autoimmune agrypnia.

    PubMed

    Frisullo, Giovanni; Della Marca, Giacomo; Mirabella, Massimiliano; Caggiula, Marcella; Broccolini, Aldobrando; Rubino, Marco; Mennuni, Gioacchino; Tonali, Pietro Attilio; Batocchi, Anna Paola

    2007-04-01

    In the serum and cerebrospinal fluid of a patient with recurrent acute episodes of respiratory crises, autonomic symptoms and total insomnia (agrypnia), we identified a novel anti-neural complement fixing antibody directed against GABA(B) receptor (GABA(B)R). Patient purified IgG recognized a band of approximately 110 kDa on protein extracts of mouse cerebellum, cortex and brainstem and immunolabelled cultured Chinese hamster ovary (CHO) cells, transfected with human GABA(B)R1 and rat GABA(B)R2 receptors. Western blot analysis of transfected CHO homogenates showed the same band using both patient purified IgG and anti-GABA(B)R1 antibody. In order to verify the pathogenic role of these purified antibodies, we injected patient IgG intrathecally into cisterna magna of C57BL/6 mice pre-implanted with EEG electrodes and we observed severe ataxia followed by breathing depression and total suppression of slow wave sleep, as evidenced by EEG recording, in a dose-dependent manner. Immunohistochemistry on brain sections of mice injected with patient IgG showed the simultaneous presence of bound human IgG and C5b-9 deposits on Purkinje cells and cerebellar granular layer. After incubation with anti-GABA(B)R antibody, a marked reduction of receptor immunostaining was found with relative sparing of neuronal architecture. In conclusion we recognized an anti-neuronal autoantibody directed against GABA(B)R that is associated with autoimmune agrypnia and we showed that our patient purified IgG was able to induce in mice experimental autoimmune agrypnia characterized by a complex neurological syndrome affecting several CNS functions.

  14. Efficacy of adalimumab in young children with juvenile idiopathic arthritis and chronic uveitis: a case series.

    PubMed

    La Torre, Francesco; Cattalini, Marco; Teruzzi, Barbara; Meini, Antonella; Moramarco, Fulvio; Iannone, Florenzo

    2014-05-24

    Juvenile idiopathic arthritis is a relatively common chronic disease of childhood, and is associated with persistent morbidity and extra-articular complications, one of the most common being uveitis. The introduction of biologic therapies, particularly those blocking the inflammatory mediator tumor necrosis factor-α, provided a new treatment option for juvenile idiopathic arthritis patients who were refractory to standard therapy such as non-steroidal anti-inflammatory drugs, corticosteroids and/or methotrexate. The first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis who failed to respond to treatment with anti-inflammatories, low-dose corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2 every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy; steroid tapering and withdrawal started after 1 month. After 2 months the patient showed good control of articular and ocular manifestations, and she remained in remission for 1 year, receiving adalimumab and methotrexate with no side effects, and showing significant improvement in growth. Case 2 was a 9-year-old boy with an 8-year history of juvenile idiopathic arthritis and uveitis that initially responded to infliximab, but relapse occurred after 2 years off therapy. After switching to adalimumab, and adjusting doses of both adalimumab and methotrexate based on body surface area, the patient showed good response and corticosteroids were tapered and withdrawn after 6 months; the patient remained in remission taking adalimumab and methotrexate. The final case was a 5-year-old girl with juvenile idiopathic arthritis for whom adalimumab was added to methotrexate therapy after three flares of uveitis. The patient had two subsequent episodes of uveitis that responded well to local therapy, but was then free of both juvenile idiopathic arthritis and uveitis symptoms, allowing methotrexate and then adalimumab to be stopped; the patient remained in drug

  15. Efficacy of adalimumab in young children with juvenile idiopathic arthritis and chronic uveitis: a case series

    PubMed Central

    2014-01-01

    Background Juvenile idiopathic arthritis is a relatively common chronic disease of childhood, and is associated with persistent morbidity and extra-articular complications, one of the most common being uveitis. The introduction of biologic therapies, particularly those blocking the inflammatory mediator tumor necrosis factor-α, provided a new treatment option for juvenile idiopathic arthritis patients who were refractory to standard therapy such as non-steroidal anti-inflammatory drugs, corticosteroids and/or methotrexate. Case presentations The first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis who failed to respond to treatment with anti-inflammatories, low-dose corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2 every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy; steroid tapering and withdrawal started after 1 month. After 2 months the patient showed good control of articular and ocular manifestations, and she remained in remission for 1 year, receiving adalimumab and methotrexate with no side effects, and showing significant improvement in growth. Case 2 was a 9-year-old boy with an 8-year history of juvenile idiopathic arthritis and uveitis that initially responded to infliximab, but relapse occurred after 2 years off therapy. After switching to adalimumab, and adjusting doses of both adalimumab and methotrexate based on body surface area, the patient showed good response and corticosteroids were tapered and withdrawn after 6 months; the patient remained in remission taking adalimumab and methotrexate. The final case was a 5-year-old girl with juvenile idiopathic arthritis for whom adalimumab was added to methotrexate therapy after three flares of uveitis. The patient had two subsequent episodes of uveitis that responded well to local therapy, but was then free of both juvenile idiopathic arthritis and uveitis symptoms, allowing methotrexate and then adalimumab to be

  16. Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis.

    PubMed

    Bichler, J; Benseler, S M; Krumrey-Langkammerer, M; Haas, J-P; Hügle, B

    2015-01-01

    Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy. A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution. A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008). Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

  17. Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients.

    PubMed

    Díaz-Llopis, Manuel; Salom, David; Garcia-de-Vicuña, Carmen; Cordero-Coma, Miguel; Ortega, Gabriela; Ortego, Norberto; Suarez-de-Figueroa, Marta; Rio-Pardo, Maria J; Fernandez-Cid, Carlos; Fonollosa, Alex; Blanco, Ricardo; Garcia-Aparicio, Angel M; Benitez-Del-Castillo, Jose M; Olea, Jose L; Arevalo, J Fernando

    2012-08-01

    To evaluate adalimumab therapy in refractory uveitis. Prospective case series. A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other systemic immunosuppressive drug participated. Patients received a 40 mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6). Degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), visual acuity (logarithm of the minimal angle of resolution [logMAR]), and macular thickness (optical coherence tomography). There were 61 men and 70 women (mean age, 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçet's disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82% of patients and in the vitreous cavity in 59% of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (P < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) μ at baseline versus 240 (36) μ at the 6-month visit (P < 0.001). Visual acuity improved by -0.3 logMAR in 32 of 150 eyes (21.3%) and worsened by +0.3 logMAR (-15 letters) in 5 eyes (3.3%). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (P < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 [5.05] vs 5.40 [4.43]; P < 0.001). Six months after the initiation of the study, 111 patients (85%) were able to reduce at least 50% of their baseline immunosuppression load. Only 9 patients (6.9%) had severe relapses

  18. The role of Leptospira spp. in horses affected with recurrent uveitis in the UK.

    PubMed

    Malalana, F; Blundell, R J; Pinchbeck, G L; Mcgowan, C M

    2017-11-01

    Equine recurrent uveitis (ERU) is a common cause of ocular pain and blindness in horses. Leptospira spp. have been commonly implicated in the pathophysiology of ERU in mainland Europe and the USA. No recent studies have been carried out in the UK, but Leptospira is reported not to be a major factor in the aetiology of ERU in the UK. To establish the prevalence of Leptospira-associated ERU in the UK and to identify the serovars involved in these cases; to compare serum vs. aqueous humour antibody levels in cases and controls in order to confirm the diagnosis of Leptospira-associated ERU, and to assess the usefulness of serology alone as a confirmatory test for Leptospira-associated ERU in the UK. Case-control study. Eyes enucleated for clinical reasons in ERU-affected horses were collected. Blood and aqueous humour were obtained to determine antibody levels against a variety of Leptospira serovars and C-values (aqueous humour value/serum value) were calculated. In addition, eyes, blood and aqueous humour were obtained from control cases for comparison. Histopathology was performed in all eyes to confirm uveitis in each case. Differences in seroprevalences between ERU and control cases and between Leptospira- and non-Leptospira-associated ERU cases were calculated. A total of 30 ERU and 43 control eyes were analysed. Of the ERU eyes, only two had a C-value of >4 (prevalence of Leptospira-associated uveitis: 6.7%). Serovars hardjo and javanica were detected. There was no difference in seroprevalence between horses with uveitis and control cases (65.5% and 41.9%, respectively; P = 0.11) or between Leptospira- and non-Leptospira-associated uveitis cases (100% and 63.0%, respectively; P = 0.52). The study was limited by low case numbers. Eyes were presented at different stages of disease. The only test used to detect Leptospira was the microscopic agglutination test. Leptospira-associated ERU is uncommon in the UK. Serology alone may not help to definitively diagnose

  19. Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis.

    PubMed

    Ramanan, Athimalaipet V; Dick, Andrew D; Jones, Ashley P; McKay, Andrew; Williamson, Paula R; Compeyrot-Lacassagne, Sandrine; Hardwick, Ben; Hickey, Helen; Hughes, Dyfrig; Woo, Patricia; Benton, Diana; Edelsten, Clive; Beresford, Michael W

    2017-04-27

    Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis. In this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria. The prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo (10.07 events per patient-year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient-year [95% CI, 5.26 to 7.77]), as were serious adverse events (0.29 events per patient-year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient-year [95% CI, 0.00 to 0.40]). Adalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab

  20. Silibinin treatment prevents endotoxin-induced uveitis in rats in vivo and in vitro.

    PubMed

    Chen, Ching-Long; Chen, Jiann-Torng; Liang, Chang-Min; Tai, Ming-Cheng; Lu, Da-Wen; Chen, Yi-Hao

    2017-01-01

    Uveitis, an intraocular inflammatory disease, occurs mostly in young people and can result in the loss of socioeconomic capabilities. Silibinin has been shown to exert anti-inflammatory effects in human retinal pigment epithelial (RPE) cells. The present study investigated the anti-inflammatory effect of silibinin pretreatment on endotoxin-induced uveitis (EIU) in rats and the mechanisms by which it exerts these effects. Uveitis was induced via injection of lipopolysaccharides (LPS) into Lewis rats. Twenty-four hours after the LPS injection, histological examination showed that silibinin decreased inflammatory cell infiltration in the anterior segment of the eyes of LPS-treated rats. Analyses of the aqueous humor showed that silibinin decreased cell infiltration, protein concentration, nitric oxide (NO), and prostaglandin (PG)-E2 production. Western blot analysis indicated that silibinin decreased the expression of inducible NO synthase (iNOS), cyclooxygenase (COX-2), and phosphorylated IkB in the iris-ciliary body (ICB). Immunohistochemistry showed that silibinin decreased intercellular adhesion molecule (ICAM-1) expression in the ICB. In addition, western blot analysis showed that silibinin attenuated the expression of iNOS, COX-2, ICAM-1, and nuclear p65 in LPS-treated RAW cells. In conclusion, silibinin pretreatment prevents EIU and the subsequent production of proinflammatory mediators and ICAM-1, at least in part, by blocking the NF-κB-dependent signaling pathway both in vivo and in vitro. These effects may contribute to the silibinin-mediated preventive effects on intraocular inflammatory diseases such as acute uveitis.

  1. Silibinin treatment prevents endotoxin-induced uveitis in rats in vivo and in vitro

    PubMed Central

    Chen, Ching-Long; Chen, Jiann-Torng; Liang, Chang-Min; Tai, Ming-Cheng; Lu, Da-Wen; Chen, Yi-Hao

    2017-01-01

    Uveitis, an intraocular inflammatory disease, occurs mostly in young people and can result in the loss of socioeconomic capabilities. Silibinin has been shown to exert anti-inflammatory effects in human retinal pigment epithelial (RPE) cells. The present study investigated the anti-inflammatory effect of silibinin pretreatment on endotoxin-induced uveitis (EIU) in rats and the mechanisms by which it exerts these effects. Uveitis was induced via injection of lipopolysaccharides (LPS) into Lewis rats. Twenty-four hours after the LPS injection, histological examination showed that silibinin decreased inflammatory cell infiltration in the anterior segment of the eyes of LPS-treated rats. Analyses of the aqueous humor showed that silibinin decreased cell infiltration, protein concentration, nitric oxide (NO), and prostaglandin (PG)-E2 production. Western blot analysis indicated that silibinin decreased the expression of inducible NO synthase (iNOS), cyclooxygenase (COX-2), and phosphorylated IkB in the iris-ciliary body (ICB). Immunohistochemistry showed that silibinin decreased intercellular adhesion molecule (ICAM-1) expression in the ICB. In addition, western blot analysis showed that silibinin attenuated the expression of iNOS, COX-2, ICAM-1, and nuclear p65 in LPS-treated RAW cells. In conclusion, silibinin pretreatment prevents EIU and the subsequent production of proinflammatory mediators and ICAM-1, at least in part, by blocking the NF-κB–dependent signaling pathway both in vivo and in vitro. These effects may contribute to the silibinin-mediated preventive effects on intraocular inflammatory diseases such as acute uveitis. PMID:28376126

  2. Unresolved issues in theories of autoimmune disease using myocarditis as a framework

    PubMed Central

    Root-Bernstein, Robert; Fairweather, DeLisa

    2014-01-01

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. PMID:25484004

  3. Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

    PubMed

    Root-Bernstein, Robert; Fairweather, DeLisa

    2015-06-21

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Intravitreal Adalimumab in Active Noninfectious Uveitis: A Pilot Study.

    PubMed

    Hamam, Rola N; Barikian, Anita W; Antonios, Rafic S; Abdulaal, Marwan R; Alameddine, Ramzi M; El Mollayess, Georges; Mansour, Ahmad M

    2016-06-01

    To evaluate the short-term efficacy of intravitreal adalimumab (IVA) for the treatment of eyes with active noninfectious uveitis. Consecutive eyes with active noninfectious uveitis were injected with IVA at 0, 2, then every 4 weeks for total of 26 weeks. Six out of 7 patients (12 of 13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment. Seven out of 12 eyes had improvement of ≥2 ETDRS lines. Three out of three eyes had resolution of anterior chamber cells. And 9 of 10 eyes with vitreous haze had zero haze at 26 weeks. Five out of 8 eyes with macular edema had complete resolution. Median fluorescein angiography score improved from 14 to 4 on last follow-up. IVA was effective in controlling the inflammation, decreasing the macular edema, and improving the best corrected visual acuity in the majority of eyes in this series.

  5. What is new HLA-B27 acute anterior uveitis?

    PubMed

    Wakefield, Denis; Chang, John H; Amjadi, Shahriar; Maconochie, Zoe; Abu El-Asrar, Ahmed; McCluskey, Peter

    2011-04-01

    Acute anterior uveitis (AAU) is the most common form of uveitis, accounting for approximately 90% of all cases. Half of all cases of AAU are HLA-B27 positive. The disease is typically acute in onset, unilateral, nongranulomatous inflammation involving the iris and ciliary body, with a tendency to recurrent attacks. Approximately 50% of all patients with HLA-B27 AAU develop an associated seronegative arthritis (SNA), while approximately 25% of the patients initially diagnosed with HLA-B27 SNA develop AAU. Environmental factors play a critical role in the pathogenesis of AAU; in particular, bacterial triggers have been strongly implicated in the development of this disease. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment for AAU. Salazopirine and methotrexate are effective in decreasing recurrent attacks. Biological agents such as anti-TNF and anti-CD20 therapy may be effective in refractory severe AU but are rarely required.

  6. Huperzine A ameliorates experimental autoimmune encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice.

    PubMed

    Wang, Jun; Chen, Fu; Zheng, Peng; Deng, Weijuan; Yuan, Jia; Peng, Bo; Wang, Ruochen; Liu, Wenjun; Zhao, Hui; Wang, Yanqing; Wu, Gencheng

    2012-07-01

    Huperzine A (HupA), a sesquiterpene alkaloid and a potent and reversible inhibitor of acetylcholinesterase, possesses potential anti-inflammatory properties and is used for the treatment of certain neurodegenerative diseases such as Alzheimer's disease. However, it is still unknown whether this chemical is beneficial in the treatment of multiple sclerosis, a progressive inflammatory disease of the central nervous system. In this study, we examined the immunomodulatory properties of HupA in experimental autoimmune encephalomyelitis (EAE), a T-cell mediated murine model of multiple sclerosis. The following results were obtained: (1) intraperitoneal injections of HupA significantly attenuate the neurological severity of EAE in mice. (2) HupA decreases the accumulation of inflammatory cells, autoimmune-related demyelination and axonal injury in the spinal cords of EAE mice. (3) HupA down-regulates mRNA levels of the pro-inflammatory cytokines (IFN-γ and IL-17) and chemokines (MCP-1, RANTES, and TWEAK) while enhancing levels of anti-inflammatory cytokines (IL-4 and IL-10) in the spinal cords of EAE mice. (4) HupA inhibits MOG(35-55) stimulation-induced T-cell proliferation and IFN-γ and IL-17 secretion in cultured splenocytes. (5) HupA inhibition of T-cell proliferation is reversed by the nicotinic acetylcholinergic receptor antagonist mecamylamine. We conclude that HupA can ameliorate EAE by suppressing autoimmune responses, inflammatory reactions, subsequent demyelination and axonal injury in the spinal cord. Therefore, HupA may have a potential therapeutic value for the treatment of multiple sclerosis and as a neuroimmunomodulatory drug to control human CNS pathology. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Treatment of pediatric uveitis with adalimumab: the MERSI experience.

    PubMed

    Castiblanco, Claudia; Meese, Halea; Foster, C Stephen

    2016-04-01

    To evaluate adalimumab therapy in children with uveitis. The electronic health records of pediatric patients diagnosed with uveitis and treated with adalimumab therapy were reviewed retrospectively. Demographic information, site and degree of intraocular inflammation, visual acuity, underlying systemic disorders, duration of therapy, side effects, and ability to obtain steroid-free remission were recorded. A total of 17 patients were included, 16 patients with anterior uveitis and 1 with panuveitis; 14 patients had bilateral disease. Juvenile idiopathic arthritis had been diagnosed in 14 patients, sarcoidosis in 1 patient, and idiopathic etiology in 2 patients. Of the 17 patients, 13 (about 77%) achieved steroid-free remission, and 4 did not. Six patients flared after discontinuation of adalimumab, with evidence of inflammation noted 3-7 months later. Adalimumab therapy was of 12-64 months' duration (mean, 36 months). At the time of initiation, 14 patients were using other agents concomitantly with adalimumab; 3 patients were on adalimumab monotherapy. At 1 year's follow-up, 12 patients were using combination therapy, and 3 patients were on adalimumab monotherapy: 11 patients had no evidence of inflammation. Side effects included pain at site of injection in 3 patients, anemia in 1 patient, and depression in 1 patient. In our study cohort, adalimumab was effective in inducing steroid-free remission. It was well tolerated, especially in combination with other immunomodulatory agents. The dosing and the interval can be adjusted to further improve inflammation control. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  8. Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical Cogan syndrome.

    PubMed

    Kolomeyer, Anton M; Kodati, Shyam

    2015-12-01

    To report a case of lamotrigine-induced tubulointerstitial nephritis and uveitis (TINU)-atypical Cogan syndrome. Case report. A 16-year-old boy with traumatic brain injury and seizures presented to the emergency department with facial swelling, rash, and back pain several days after increasing lamotrigine dose secondary to a breakthrough seizure. Creatinine, urine β2 microglobulin, and eosinophils were elevated. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, and complement were normal. Renal biopsy showed acute granulomatous tubulointerstitial nephritis. Lamotrigine was discontinued, intravenous steroids were initiated, and the patient was discharged on Ativan and prednisone. Subsequently, he was diagnosed with bilateral anterior uveitis (vision 20/30 bilaterally) and started on prednisolone and cyclopentolate. Two months later, he developed a branch retinal artery occlusion in the right eye (vision 20/70) and bilateral ocular hypertension for which timolol-brimonidine and dorzolamide were added. Neuroimaging and hypercoagulability workup was unremarkable. Vision and intraocular pressure improved, while uveitis remained recalcitrant. Several months later, the patient developed central serous retinopathy in the right eye (vision 20/30). Prednisone was stopped but restarted due to methotrexate intolerance. A month later, he reported dizziness and was diagnosed with severe bilateral sensorineural hearing loss. Brain magnetic resonance imaging showed foci of perivascular, subcortical, and cochlear enhancement. Transtympanic Decadron injections and infliximab infusions were initiated. At the final visit, vision remained at 20/30 with trace anterior chamber reaction bilaterally while on timolol-brimonidine, dorzolamide, and prednisolone. An idiosyncratic drug reaction should be considered in the differential diagnosis of TINU-atypical Cogan syndrome.

  9. Autoimmune disease: A role for new anti-viral therapies?

    PubMed

    Dreyfus, David H

    2011-12-01

    Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. [Anterior uveitis caused by electrical discharge in whole body injuries (fifteen years study)].

    PubMed

    Krásný, J; Brož, L; Kripner, J

    2013-10-01

    To inform about clinical analysis of early ophthalmologic complication (uveitis) in patients sustained electric discharge injury. The authors refer about fifteen years follow-up of pediatric patients at the Department of Burns Medicine, 3rd Medical Faculty, Charles University in Prague, Czech Republic, E.U., with electric discharge injury, in which the anterior uveitis was detected. Out of 43 patients after electric discharge injury, the always-unilateral iritis (iridocyclitis) was diagnosed in four (9 %) patients according to thorough going follow-up after first accidental diagnosis in the year 1998. Out of four boys aged 12 - 15 years, the first two were injured during the "play" - due to the contact with electrical trolley wire while running on railroad wagons roofs, and the two others were stuck by lighting under a tree by secondary electrical discharge. More serious skin burns were noticed in high-voltage current injury - 69 % or 55 % of body surface respectively, with the necessity of skin transplantation. The same was necessary in one boy injured by lighting with burns of 25 % of body surface, while the last one had on the skin the lighting signs only. In most of the patients, the resuscitation care due to unconsciousness and posttraumatic shock was necessary. The anterior uveitis was diagnosed subsequently, after initial preliminary diagnoses as conjunctivitis, episcleritis, or ophthalmia electrical. The iritis without visual function decrease was discovered in few days after the injury in three patients. Treatment and results: The inflammation was in these cases treated with short-term application of mydriatic and corticosteroid eye drops. Once only, the uveitis appeared after two months during the patients hospitalization and then the signs of iridocyclitis in the anterior chamber worsened and caused visual acuity decrease to hand movement in front of the eye. The condition was successfully treated by means of parabulbar betamethasone injection and long

  11. Prolonged Stimulation of a Brainstem Raphe Region Attenuates Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Madsen, Pernille M.; Sloley, Stephanie S.; Vitores, Alberto A.; Carballosa-Gautam, Melissa M.; Brambilla, Roberta; Hentall, Ian D.

    2017-01-01

    Multiple sclerosis (MS), a neuroinflammatory disease, has few treatment options, none entirely adequate. We studied whether prolonged electrical stimulation of a hindbrain region (the nucleus raphe magnus) can attenuate experimental autoimmune encephalomyelitis, a murine model of MS induced by MOG35-55 injection. Eight days after symptoms emerged, a wireless electrical stimulator with a connectorless protruding microelectrode was implanted cranially, and daily intermittent stimulation of awake, unrestrained mice began immediately. The thoracic spinal cord was analyzed for changes in histology (on day 29) and gene expression (on day 37), with a focus on myelination and cytokine production. Controls, with inactive implants, showed a phase of disease exacerbation on days 19–25 that stimulation for >16 days eliminated. Prolonged stimulation also reduced infiltrating immune cells and increased numbers of myelinated axons. It additionally lowered gene expression for some pro-inflammatory cytokines (interferon gamma and tumor necrosis factor) and for platelet-derived growth factor receptor alpha, a marker of oligodendrocyte precursors, while raising it for myelin basic protein. Restorative treatments for MS might profitably consider ways to stimulate the raphe magnus, directly or via its inputs, or to emulate its serotonergic and peptidergic output. PMID:28147248

  12. Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study.

    PubMed

    Atienza-Mateo, Belén; Calvo-Río, Vanesa; Beltrán, Emma; Martínez-Costa, Lucía; Valls-Pascual, Elia; Hernández-Garfella, Marisa; Atanes, Antonio; Cordero-Coma, Miguel; Miquel Nolla, Joan; Carrasco-Cubero, Carmen; Loricera, Javier; González-Vela, María C; Vegas-Revenga, Nuria; Fernández-Díaz, Carlos; Demetrio-Pablo, Rosalía; Domínguez-Casas, Lucía C; Luis Martín-Varillas, José; Palmou-Fontana, Natalia; Hernández, José L; González-Gay, Miguel Á; Blanco, Ricardo

    2018-05-01

    To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. TCZ could be a therapeutic option in patients with BD and refractory uveitis.

  13. Autoimmunity and Gastric Cancer

    PubMed Central

    Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

    2018-01-01

    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

  14. Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling.

    PubMed

    Li, Wen; Zhang, Zhihui; Zhang, Kai; Xue, Zhenyi; Li, Yan; Zhang, Zimu; Zhang, Lijuan; Gu, Chao; Zhang, Qi; Hao, Junwei; Da, Yurong; Yao, Zhi; Kong, Ying; Zhang, Rongxin

    2016-10-01

    Arctigenin is a herb compound extract from Arctium lappa and is reported to exhibit pharmacological properties, including neuronal protection and antidiabetic, antitumor, and antioxidant properties. However, the effects of arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are still unclear. In this study, we demonstrated that arctigenin-treated mice are resistant to EAE; the clinical scores of arctigenin-treated mice are significantly reduced. Histochemical assays of spinal cord sections also showed that arctigenin reduces inflammation and demyelination in mice with EAE. Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by arctigenin in vivo. In addition, the Th1 cytokine IFN-γ and transcription factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription factor ROR-γt are significantly suppressed upon arctigenin treatment in vitro and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with EAE, while Th1 cells do not significantly change. Besides, arctigenin significantly restrains the differentiation of Th17 cells. We further demonstrate that arctigenin activates AMPK and inhibits phosphorylated p38, in addition, upregulates PPAR-γ, and finally suppresses ROR-γt. These findings suggest that arctigenin may have anti-inflammatory and immunosuppressive properties via inhibiting Th17 cells, indicating that it could be a potential therapeutic drug for multiple sclerosis or other autoimmune inflammatory diseases.

  15. Intravenous administration of bone marrow-derived mesenchymal stem cells induces a switch from classical to atypical symptoms in experimental autoimmune encephalomyelitis.

    PubMed

    Kurte, Mónica; Bravo-Alegría, Javiera; Torres, Alexander; Carrasco, Vania; Ibáñez, Cristina; Vega-Letter, Ana María; Fernández-O'Ryan, Catalina; Irarrázabal, Carlos E; Figueroa, Fernando E; Fuentealba, Rodrigo A; Riedel, Claudia; Carrión, Flavio

    2015-01-01

    Potent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect of MSCs administration at different disease stages in experimental autoimmune encephalomyelitis (EAE). Classical and atypical scores of EAE, associated with Th1 and Th17 response, respectively, and also Treg lymphocytes, were evaluated. MSCs administration at the onset (EAE+MSConset) induced an important amelioration of the clinical signs and less lasting effect at the peak of EAE (EAE+MSCpeak). No effect was observed when MSCs were applied after EAE stabilization (EAE+MSClate). Surprisingly, EAE atypical signs were detected in EAE+MSCpeak and EAE+MSClate mice. However, no correlation was found in Th17/Th1 ratio. Interestingly, regardless of time administration, MSCs significantly reduced IL-6 and also T-bet, RORγT, and Foxp3 mRNA levels in brain samples of EAE mice. The downregulation of IL-6 could restore the well-functioning of the blood-brain barrier of EAE mice, correlated with a decreased number of brain infiltrating leukocytes. These results suggest that the inflammatory status is important to be considered for administering MSCs in autoimmune pathologies, leading to a further research to clarify the effect of MSCs for multiple sclerosis.

  16. Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Kurte, Mónica; Bravo-Alegría, Javiera; Torres, Alexander; Carrasco, Vania; Ibáñez, Cristina; Vega-Letter, Ana María; Fernández-O'Ryan, Catalina; Irarrázabal, Carlos E.; Figueroa, Fernando E.; Fuentealba, Rodrigo A.; Riedel, Claudia; Carrión, Flavio

    2015-01-01

    Potent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect of MSCs administration at different disease stages in experimental autoimmune encephalomyelitis (EAE). Classical and atypical scores of EAE, associated with Th1 and Th17 response, respectively, and also Treg lymphocytes, were evaluated. MSCs administration at the onset (EAE+MSConset) induced an important amelioration of the clinical signs and less lasting effect at the peak of EAE (EAE+MSCpeak). No effect was observed when MSCs were applied after EAE stabilization (EAE+MSClate). Surprisingly, EAE atypical signs were detected in EAE+MSCpeak and EAE+MSClate mice. However, no correlation was found in Th17/Th1 ratio. Interestingly, regardless of time administration, MSCs significantly reduced IL-6 and also T-bet, RORγT, and Foxp3 mRNA levels in brain samples of EAE mice. The downregulation of IL-6 could restore the well-functioning of the blood-brain barrier of EAE mice, correlated with a decreased number of brain infiltrating leukocytes. These results suggest that the inflammatory status is important to be considered for administering MSCs in autoimmune pathologies, leading to a further research to clarify the effect of MSCs for multiple sclerosis. PMID:25838828

  17. Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

    PubMed

    Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

    2015-03-01

    The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells. © 2014 British Society for Immunology.

  18. General principles for the treatment of non-infectious uveitis.

    PubMed

    Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto; García-Delpech, Salvador; Salom-Alonso, David

    2009-09-01

    Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to develop the role of corticosteroid-saving agents. These can be organized in four other steps: Cyclosporine and Methotrexate in a second one; Azathioprine, Mycophenolate Mofetil and Tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a theoretical last one with Cyclophosphamide and Chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non infectious posterior uveitis.

  19. A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.

    PubMed

    Gilger, Brian C; Salmon, Jacklyn H; Wilkie, David A; Cruysberg, Lars P J; Kim, Jonghyeon; Hayat, Matt; Kim, Hyuncheol; Kim, Stephanie; Yuan, Peng; Lee, Susan S; Harrington, Susan M; Murray, Patrick R; Edelhauser, Henry F; Csaky, Karl G; Robinson, Michael R

    2006-06-01

    To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

  20. Early treatment of tuberculous uveitis improves visual outcome: a 10-year cohort study.

    PubMed

    Anibarro, Luis; Cortés, Eliana; Chouza, Ana; Parafita-Fernández, Alberto; García, Juan Carlos; Pena, Alberto; Fernández-Cid, Carlos; González-Fernández, África

    2018-06-04

    Diagnosis of tuberculous uveitis (TBU) is often challenging and is usually made after excluding other causes of uveitis. We analysed the characteristics of TBU and variables associated with visual outcome. A retrospective, observational analysis was performed in patients with presumptive TBU who were started on specific TB treatment between January 2006 and June 2016. Demographic, clinical, radiological, analytical and ophthalmic examination variables were studied. After completing TB treatment, a follow-up of at least 9 months was performed. A univariate and logistic regression analysis was applied to identify the variables associated with visual acuity and recurrences of uveitis. Forty affected eyes of 24 individuals were identified; 79% of patients were diagnosed during the last 3 years of the study period. Median delay from onset of symptoms to diagnosis was 12 weeks. Loss of visual acuity was the most frequent symptom (87.5%). Posterior uveitis was the most frequent localization (72.9%); 19 patients (79.2%) presented at least one of the Gupta signs predictive of TBU, but there were no confirmed diagnoses. There was improvement in visual acuity in 74.4% of the eyes, but a complete response was achieved only in 56.4%. There was recurrence in two patients. The initiation of treatment ≥ 24 weeks after onset of symptoms was significantly associated with no improvement (p = 0.026). TBU can cause permanent damage to visual acuity, particularly in patients with delayed diagnosis. A prompt initiation of systemic TB treatment is essential to improve visual prognosis.