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Sample records for active sle patients

  1. Increased serum levels of soluble l-selectin (CD62L) in patients with active systemic lupus erythematosus (SLE)

    PubMed Central

    Font, J; Pizcueta, P; Ramos-Casals, M; Cervera, R; García-Carrasco, M; Navarro, M; Ingelmo, M; Engel, P

    2000-01-01

    The adhesion molecule l-selectin (CD62L) mediates lymphocyte recirculation and leucocyte rolling on vascular endothelium at sites of inflammation. Serum levels of soluble l-selectin (sl-selectin) were measured in patients with SLE in order to relate these levels to clinical activity and immunological parameters. An ELISA was used to detect the soluble form of human l-selectin (CD62L) in 42 patients with SLE and in 33 healthy individuals. The mean ± s.e.m. values of sl-selectin were 1285 ± 121 ng/ml for patients with SLE and 986 ± 180 ng/ml for healthy blood donors, but there was no significant difference. When patients with active SLE were analysed, higher levels of circulating sl-selectin were found when compared with patients without activity (1497 ± 167 ng/ml versus 941 ± 150 ng/ml; P = 0.028). We found a significant correlation between the levels of sl-selectin and of dsDNA antibodies (r = 0.36, P = 0.044) and between levels of sl-selectin and SLE Disease Activity Index (SLEDAI) score (r = 0.42, P = 0.003). Patients with active SLE studied cross-sectionally showed significant elevations of sl-selectin (CD62L) compared with controls. Thus, the levels of this soluble adhesion molecule correlated with active disease and levels of anti-dsDNA antibodies. PMID:10606979

  2. Characterization of the Phosphoproteome in SLE Patients

    PubMed Central

    Huang, Jianrong; Dai, Yong

    2012-01-01

    Protein phosphorylation is a complex regulatory event that is involved in the signaling networks that affect virtually every cellular process. The protein phosphorylation may be a novel source for discovering biomarkers and drug targets. However, a systematic analysis of the phosphoproteome in patients with SLE has not been performed. To clarify the pathogenesis of systemic lupus erythematosus (SLE), we compared phosphoprotein expression in PBMCs from SLE patients and normal subjects using proteomics analyses. Phosphopeptides were enriched using TiO2 from PBMCs isolated from 15 SLE patients and 15 healthy subjects and then analyzed by automated LC-MS/MS analysis. Phosphorylation sites were identified and quantitated by MASCOT and MaxQuant. A total of 1035 phosphorylation sites corresponding to 618 NCBI-annotated genes were identified in SLE patients compared with normal subjects. Differentially expressed proteins, peptides and phosphorylation sites were then subjected to bioinformatics analyses. Gene ontology(GO) and pathway analyses showed that nucleic acid metabolism, cellular component organization, transport and multicellular organismal development pathways made up the largest proportions of the differentially expressed genes. Pathway analyses showed that the mitogen-activated protein kinase (MAPK) signaling pathway and actin cytoskeleton regulators made up the largest proportions of the metabolic pathways. Network analysis showed that rous sarcoma oncogene (SRC), v-rel reticuloendotheliosis viral oncogene homolog A (RELA), histone deacetylase (HDA1C) and protein kinase C, delta (PRKCD) play important roles in the stability of the network. These data suggest that aberrant protein phosphorylation may contribute to SLE pathogenesis. PMID:23285258

  3. Sex Differences in Monocyte Activation in Systemic Lupus Erythematosus (SLE)

    PubMed Central

    Jiang, Wei; Zhang, Lumin; Lang, Ren; Li, Zihai; Gilkeson, Gary

    2014-01-01

    Introduction TLR7/8 and TLR9 signaling pathways have been extensively studied in systemic lupus erythematosus (SLE) as possible mediators of disease. Monocytes are a major source of pro-inflammatory cytokines and are understudied in SLE. In the current project, we investigated sex differences in monocyte activation and its implications in SLE disease pathogenesis. Methods Human blood samples from 27 healthy male controls, 32 healthy female controls, and 25 female patients with SLE matched for age and race were studied. Monocyte activation was tested by flow cytometry and ELISA, including subset proportions, CD14, CD80 and CD86 expression, the percentage of IL-6-producing monocytes, plasma levels of sCD14 and IL-6, and urine levels of creatinine. Results Monocytes were significantly more activated in women compared to men and in patients with SLE compared to controls in vivo. We observed increased proportions of non-classic monocytes, decreased proportions of classic monocytes, elevated levels of plasma sCD14 as well as reduced surface expression of CD14 on monocytes comparing women to men and lupus patients to controls. Plasma levels of IL-6 were positively related to sCD14 and serum creatinine. Conclusion Monocyte activation and TLR4 responsiveness are altered in women compared to men and in patients with SLE compared to controls. These sex differences may allow persistent systemic inflammation and resultant enhanced SLE susceptibility. PMID:25485543

  4. Association of the interferon signature metric with serological disease manifestations but not global activity scores in multiple cohorts of patients with SLE

    PubMed Central

    Kennedy, William P; Maciuca, Romeo; Wolslegel, Kristen; Tew, Wei; Abbas, Alexander R; Chaivorapol, Christina; Morimoto, Alyssa; McBride, Jacqueline M; Brunetta, Paul; Richardson, Bruce C; Davis, John C; Behrens, Timothy W; Townsend, Michael J

    2015-01-01

    Objectives The interferon (IFN) signature (IS) in patients with systemic lupus erythematosus (SLE) includes over 100 genes induced by type I IFN pathway activation. We developed a method to quantify the IS using three genes—the IS metric (ISM)—and characterised the clinical characteristics of patients with SLE with different ISM status from multiple clinical trials. Methods Blood microarray expression data from a training cohort of patients with SLE confirmed the presence of the IS and identified surrogate genes. We assayed these genes in a quantitative PCR (qPCR) assay, yielding an ISM from the IS. The association of ISM status with clinical disease characteristics was assessed in patients with extrarenal lupus and lupus nephritis from four clinical trials. Results Three genes, HERC5, EPSTI and CMPK2, correlated well with the IS (p>0.96), and composed the ISM qPCR assay. Using the 95th centile for healthy control data, patients with SLE from different studies were classified into two ISM subsets—ISM-Low and ISM-High—that are longitudinally stable over 36 weeks. Significant associations were identified between ISM-High status and higher titres of anti-dsDNA antibodies, presence of anti extractable nuclear antigen autoantibodies, elevated serum B cell activating factor of the tumour necrosis factor family (BAFF) levels, and hypocomplementaemia. However, measures of overall clinical disease activity were similar for ISM-High and ISM-Low groups. Conclusions The ISM is an IS biomarker that divides patients with SLE into two subpopulations—ISM-High and ISM-Low—with differing serological manifestations. The ISM does not distinguish between high and low disease activity, but may have utility in identifying patients more likely to respond to treatment(s) targeting IFN-α. Clinicaltrials.gov registration number NCT00962832. PMID:25861459

  5. Effect of targeted nursing applied to SLE patients

    PubMed Central

    ZHANG, XIANGYING; TIAN, YALI; LI, JUNBAO; ZHAO, XINGLI

    2016-01-01

    The aim of the present study was to evaluate the efficacy of targeted nursing for patients with systemic lupus erythematosus (SLE). A total of 114 patients clinically diagnosed with stable SLE were prospectively selected. The patients were randomly divided into the regular special nursing group, comprising 56 patients and the targeted nursing group (i.e., taylor made according to different pathogenic conditions and treatment period), comprising 58 patients. The patients received standard medical treatment for SLE, irrespective of their group, and the efficacy of targeted nursing on disease activity, incidence of complications, therapeutic compliance, quality of life and nursing satisfaction was compared with regular special nursing. The patients were followed up for a period of 20 months. The results showed that, disease activity and injury index score and incidence of complications were significantly less in the targeted nursing group than in the regular special nursing group (P<0.05). Additionally, therapeutic compliance, quality of life score and nursing content satisfaction were significantly higher in the targeted nursing group in comparison with the regular special nursing group (P<0.05). Thus, the results indicated that targeted nursing significantly improved therapeutic compliance and quality of life, and simultaneously, reduced complications and disease activity in patients receiving standard treatment for SLE. PMID:27284302

  6. The effect of Ramadan fasting on quiescent systemic lupus erythematosus (SLE) patients' disease activity, health quality of life and lipid profile: a pilot study.

    PubMed

    Goharifar, Hamid; Faezi, Seyedeh Tahereh; Paragomi, Pedram; Montazeri, Ali; Banihashemi, Arash Tehrani; Akhlaghkhah, Maryam; Abdollahi, Bahar Sadeghi; Kamazani, Zahra; Akbarian, Mahmood

    2015-08-01

    SLE is a common autoimmune disease with considerable morbidity. Ramadan fasting is a religious custom Muslims regularly practice. We aimed to evaluate the effect of Ramadan fasting on SLE patients' disease activity, health quality of life and lipid profile. We conducted this case control study as a pilot study in 40 quiescent SLE patients, 21 cases who decided to fast and 19 controls who decided not to have Ramadan fasting between August and November 2009 in lupus unit of Rheumatology Research Center in Tehran University of Medical Sciences, Iran. They were assessed for SLE Disease Activity Index, lipid profile and quality of life with Short-Form 36 (SF-36) Health Survey, 1 day before Ramadan, the day after and 3 months after Ramadan fasting. After 24.1 ± 5.4 (mean ± SD) days of fasting, anti-ds DNA increased for 0.34 ± 0.41 mmol/dL in cases versus 0.07 ± 0.31 in controls (P = 0.026). Likewise C3 increased more dramatically in cases (16.8 ± 17.5 vs. 2.3 ± 13.2 mg/dL, P = 0.006). Three months after fasting, anti-ds DNA was still increased 0.28 ± 0.46 mmol/dL in cases while a 0.02 ± 0.43 mmol/dL drop in controls was detected (P = 0.04). On the contrary, C3 returned to baseline. These changes were not accompanied with significant changes in disease activity and health quality of life. Ramadan fasting had no effect on lipid profile except for delayed total cholesterol decrease in cases in comparison with controls (16.4 ± 29.4 decrease vs. 4.6 ± 23.9 mg/dL decrease, P = 0.018). Ramadan fasting probably has no detrimental effect on SLE patients' disease activity and their quality of life in the quiescent phase of disease. PMID:25972126

  7. Pregnancy Outcomes in Chinese Patients with Systemic Lupus Erythematosus (SLE): A Retrospective Study of 109 Pregnancies.

    PubMed

    Ku, Ming; Guo, Shuiming; Shang, Weifeng; Li, Qing; Zeng, Rui; Han, Min; Ge, Shuwang; Xu, Gang

    2016-01-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women during their reproductive years. The interaction between SLE and pregnancy remains debated. The objective of this study was to analyze the fetal and maternal outcomes of Chinese women with SLE. A total of 109 pregnancies in 83 SLE patients from June 2004 to June 2014 at a tertiary university hospital were reviewed retrospectively. Patients' characteristics, clinical and laboratory data during pregnancy were obtained from electronic medical records. After exclusion of elective abortions, the live birth rate was 61.5%. Significantly, APS (antiphospholipid syndrome), disease activity, hypertension, hypocomplementemia, thrombocytopenia, and anemia during pregnancy were more commonly observed in fetal loss pregnancies than in live birth pregnancies. Compared to the 64 women with a history of SLE, 19 women with new-onset lupus during pregnancy had worse pregnancy outcome. Furthermore, the 64 patients with a history of SLE were divided into lupus nephritis group and SLE group (non-renal involvement). We found that the lupus nephritis group had worse maternal outcome than the SLE group. We conclude that new-onset lupus during pregnancy predicts both adverse maternal and fetal outcomes, while a history of lupus nephritis predicts adverse maternal outcomes. It is essential to provide SLE women with progestational counseling and regular multispecialty care during pregnancy. PMID:27442513

  8. Pregnancy Outcomes in Chinese Patients with Systemic Lupus Erythematosus (SLE): A Retrospective Study of 109 Pregnancies

    PubMed Central

    Ku, Ming; Guo, Shuiming; Shang, Weifeng; Li, Qing; Zeng, Rui; Han, Min; Ge, Shuwang; Xu, Gang

    2016-01-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women during their reproductive years. The interaction between SLE and pregnancy remains debated. The objective of this study was to analyze the fetal and maternal outcomes of Chinese women with SLE. A total of 109 pregnancies in 83 SLE patients from June 2004 to June 2014 at a tertiary university hospital were reviewed retrospectively. Patients’ characteristics, clinical and laboratory data during pregnancy were obtained from electronic medical records. After exclusion of elective abortions, the live birth rate was 61.5%. Significantly, APS (antiphospholipid syndrome), disease activity, hypertension, hypocomplementemia, thrombocytopenia, and anemia during pregnancy were more commonly observed in fetal loss pregnancies than in live birth pregnancies. Compared to the 64 women with a history of SLE, 19 women with new-onset lupus during pregnancy had worse pregnancy outcome. Furthermore, the 64 patients with a history of SLE were divided into lupus nephritis group and SLE group (non-renal involvement). We found that the lupus nephritis group had worse maternal outcome than the SLE group. We conclude that new-onset lupus during pregnancy predicts both adverse maternal and fetal outcomes, while a history of lupus nephritis predicts adverse maternal outcomes. It is essential to provide SLE women with progestational counseling and regular multispecialty care during pregnancy. PMID:27442513

  9. Subclinical hypothyroidism is a risk factor for delayed clinical complete response in patients with systemic lupus erythematosus (SLE)

    PubMed Central

    Dong, Lin; Jia, Liu; Hong, Xuezhi; Chen, Guangliang; Mo, Hanyou

    2014-01-01

    The objective of the study was to investigate whether subclinical hypothyroidism is a risk factor for a delayed clinical complete response in patients with SLE. This study included 363 patients with SLE classified according to the ACR classification criteria. These patients were divided into three groups: those who had subclinical hypothyroidism, a euthyroid state, and clinical hypothyroidism. The first group contained 41 cases with SLE and subclinical hypothyroidism, the second group contained 7 cases with SLE and clinical hypothyroidism, and the third group contained 315 positive control cases with SLE and a euthyroid state. Patients were observed for general observational parameters, and an efficacy assessment was performed using SLEDAI, PGA, and SLICC. Results: Patients in the subclinical hypothyroidism group without supplementary treatment had no higher immune activity indicators, SLE activity, and organ damage than those SLE with euthyroid state. These parameters were also no higher than in those who were given treatment in the SLE with clinical hypothyroidism group at 6 months; Immune activity indicators, SLE activity, organ damage, and remission rate were improved after 3 months’ supplementary treatment in 14 subclinical hypothyroidism cases that did not display remission non-remission cases at 6 months. Additionally, no significant difference in remission rate was observed in comparison with the group of SLE patients with a euthyroid state after 6 months’ supplementary treatment. Conclusion: Subclinical hypothyroidism can the slow remission rate of SLE. Supplementary treatment should be performed earlier to improve the remission rate. PMID:25356146

  10. Bronchoalveolar lavage cell analysis and lung function impairment in patients with systemic lupus erythematosus (SLE).

    PubMed Central

    Groen, H; Aslander, M; Bootsma, H; van der Mark, T W; Kallenberg, C G; Postma, D S

    1993-01-01

    We examined the relationship between peripheral blood and bronchoalveolar lavage (BAL) lymphocyte phenotypes and lung function in 19 patients with SLE, and evaluated their association with disease activity. Lung function assessment showed a mildly restrictive pattern with frequent impairment of transfer factor for carbon monoxide (T1,co) and diffusing capacity of the alveolocapillary membrane (Dm), of late-expiratory airflow rates and with a high prevalence of increased airway resistance. T1,co, Kco and Dm correlated inversely with the numbers of CD8+ cells and CD56+/CD16+/CD3- (NK) cells in BAL. Oxygen radical production, both by stimulated and unstimulated BAL cells and blood polymorphonuclear leucocytes (PMN) was significantly increased in SLE. In comparison with healthy controls, patients with SLE had a lower percentage of CD19+ B cells in the BAL versus an increased percentage of these cells in peripheral blood. HLA-DR expression on CD4+ and CD8+ lung lymphocytes was markedly increased in SLE. Current SLE disease activity was not associated with changes in BAL or peripheral blood lymphocyte phenotypes. Our data suggest that an ongoing cell-mediated immune response is present in the lungs in SLE, particularly involving activated CD8+ T cells and CD56+/CD16+/CD3- NK cells. It is associated with up-regulated local production of oxygen radicals and with impaired pulmonary diffusing capacity. This inflammatory process seems to be independent of general SLE disease activity. PMID:8403494

  11. CDR molecular localization of possible anti-idiotypic anti-DNA antibodies in normal subjects, patients with SLE, and SLE first-degree relatives.

    PubMed

    Williams, R W; Malone, C C; Silvestris, F

    1995-07-01

    Patients with active systemic lupus erythematosus (SLE) with disease worsening or severe flares frequently show very low levels of serum immunoglobulin G (IgG) anti-F(ab')2 antibody. Anti-F(ab')2 antibody probably represents a polyclonal collection of generic anti-idiotypic antibodies involved in immune homeostasis. We synthesized the entire variable regions of the heavy and light chains (VH and VL) of two monoclonal anti-DNA antibodies, V88 and 2A4, as overlapping 7-mers on small polypropylene pins and tested these linear segments of anti-DNA V-regions for reactivity against serum samples from 10 normal subjects with high serum IgG anti-F(ab')2, 11 normal subjects with low anti-F(ab')2, 5 patients with SLE with active uncontrolled disease, 3 patients with SLE in remission, and 8 unaffected normal first-degree SLE relatives. VH and VL regions of a human monoclonal IgG anti-rabies antibody were also tested as a control. Concordant IgG antibody reacting with the same complementarity-determining regions (CDRs) was arbitrarily scored as indicative of the presence of anti-idiotypic antibody in test serum samples. Among normal subjects with either high or low serum anti-F(ab')2 levels, 10% to 21% showed strong concordant anti-CDR reactions with either the monoclonal anti-DNA or the control monoclonal anti-rabies V-region sequences. However, all patients with active SLE showed no detectable anti-CDR-reactive antibody. Patients with SLE in remission often showed return of strong concordant anti-CDR antibody. Normal unaffected SLE relatives also showed high levels of anti-CDR reactivity for both monoclonal anti-DNA and anti-rabies antibody sequences. PMID:7602233

  12. The association between diet and glucocorticoid treatment in patients with SLE

    PubMed Central

    Lourdudoss, Cecilia; Hafström, Ingiäld; Frostegård, Johan; van Vollenhoven, Ronald

    2016-01-01

    Background Some studies suggest that the risk for and severity of systemic lupus erythematosus (SLE) can be modified by certain nutrients. The aim of this study was to investigate the association between diet and glucocorticoid (GC) treatment, as a proxy for disease activity, in patients with SLE. Methods We included 111 patients with SLE from the SLE Vascular Impact Cohort (SLEVIC). Dietary data were linked with data on GC treatment during a 2-year period. The association between diet and GC treatment was analysed with logistic regression. GC treatment and unchanged/increased doses were considered a proxy for active SLE. Results During the 2-year period, 54 patients (48.6%) had continued GC treatment. Dietary vitamin D was associated with GC treatment (OR=2.70–2.85 (95% CI 1.00 to 8.11)), whereas alcohol was inversely associated with GC treatment (OR=0.28–0.39 (95% CI 0.10 to 98)). Beta-carotene, fatty acid C18:2 and vitamin B6 were inversely associated with unchanged/increased GC dose (OR=0.29–0.30 (95% CI 0.10 to 0.90)). Finally, total energy intake was associated with GC doses >5.0 mg/day and >7.5 mg/day, explaining a direct association between 35 nutrients and higher GC dose levels (OR=2.98–23.82 (95% CI 1.01 to 203.88)). Discussion Dietary vitamin D did not protect against lupus activity. Beta-carotene, fatty acid C18:2 and vitamin B6 may protect against increased GC dose. The inverse association between alcohol intake and GC treatment/lupus activity may provide a partial explanation for the link between moderate alcohol intake and reduced risk of SLE. The association between higher dietary intake and higher GC dose levels indicated GC's influence on increasing appetite. PMID:26848399

  13. Distribution of PTPN22 polymorphisms in SLE from western Mexico: correlation with mRNA expression and disease activity.

    PubMed

    Machado-Contreras, Jesús René; Muñoz-Valle, José Francisco; Cruz, Alvaro; Salazar-Camarena, Diana Celeste; Marín-Rosales, Miguel; Palafox-Sánchez, Claudia Azucena

    2016-08-01

    Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune inflammatory disease characterized by loss of self-tolerance with hyperactivation of autoreactive T and B cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes for lymphoid-specific phosphatase (Lyp), which is a key negative regulator of T lymphocyte activation. The aim of this study was to evaluate the genetic contribution of PTPN22 -1123G>C and +1858C>T polymorphisms and their haplotypes in SLE patients, as well as mRNA expression according to -1123G>C promoter polymorphism and disease activity. One hundred and fifty SLE patients and 150 unrelated healthy controls (HC), both Mexican mestizos, were genotyped by PCR-RFLP technique for the PTPN22 -1123G>C and +1858C>T polymorphisms. PTPN22 mRNA expression levels were determined by real-time PCR from PBMCs of thirty patients with SLE and fifteen HC carrying different genotypes. Distributions of genotype and allelic frequencies were similar between SLE and HC. The most frequent alleles were -1123 G and +1858 C in both groups (69 vs. 66 % and 97 vs. 98 %, in SLE and HC, respectively). However, the recessive model of inheritance analysis showed a lower frequency of -1123 CC genotype in SLE patients (7 vs. 15 %), suggesting a protection effect to develop SLE (OR 0.41, CI 1.10-5.28, p = 0.02). Haplotype analysis showed strong linkage disequilibrium D' = 0.98 for PTPN22 -1123G>C and +1858C>T polymorphisms, but haplotypes were not associated with SLE. The PTPN22 mRNA expression did not show differences among -1123G>C genotypes; nevertheless, a significant negative correlation with disease activity was found (r = -0.64, p < 0.01). SLE inactive patients showed similar PTPN22 mRNA expression levels to healthy controls, whereas in patients with severe flare, the expression was nearly depleted. In conclusion, we found a lack of association of PTPN22 -1123G>C and +1858C>T polymorphisms with the risk of developing SLE in a Mexican

  14. Antibody binding of macromolecular DNA and RNA in the plasma of SLE patients.

    PubMed

    Krapf, F; Herrmann, M; Leitmann, W; Kalden, J R

    1989-03-01

    Plasmapheresis fluids from 20 patients with clinically active SLE, from three patients with Waldenstrom's disease, from three patients with rheumatoid arthritis, two patients with myasthenia gravis and other diseases including active systemic disorders were precipitated using polyethylene glycol 6000 (PEG). By applying ethidium bromide staining, plasma nucleic acids (PNA) could be demonstrated in PEG-precipitates of SLE patients exclusively. Purified immunoglobulins of SLE plasma precipitates were shown to form antigen-antibody complexes with PNA as demonstrated by electronmicroscopy. Further characterization of PNA by agarose gel electrophoresis revealed a molecular weight up to 20 kbp. Cesium chloride buoyant density gradients showed non-homogeneous molecules, excluding pure microbial origin. In spite of RNase digestion, the PNA contained RNA with 30-70% riboguanosine as shown by nucleoside analysis. The high amount of guanosine-rich RNA was further supported by similarities between PNA and polyriboguanylic acid in hyperchrome shifting due to thermic denaturation. HPLC analysis showed a molecular weight of ribonucleic acids of more than 60 b thus excluding mere oligonucleotides. In contrast to B-type dsDNA, PNA from SLE patients were immunogenic. Antibodies against PNA could be induced in rabbits by subcutaneous injection. The antisera thus obtained showed crossreactivity with polyriboguanylic acid and dsDNA preparations. PMID:2467774

  15. E4BP4 overexpression: a protective mechanism in CD4+ T cells from SLE patients.

    PubMed

    Zhao, Ming; Liu, Qian; Liang, Gongping; Wang, Litao; Luo, Shuangyan; Tang, Qian; Zhao, Hongjun; Su, Yuwen; Yung, Susan; Chan, Tak Mao; Lu, Qianjin

    2013-03-01

    Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of T and B lymphocytes, which trigger autoantibody production and immune-complex deposition. E4BP4, also known as NFIL3, has emerged as a major transcription factor that regulates the development and function of immune cells in a number of lineages. E4BP4 has been shown to regulate cytokines expression, and its synthesis is in turn controlled by various cytokines. To date, the roles of E4BP4 in immune dysregulation and autoimmune disorders are unclear. In this study, we demonstrated that E4BP4 expression is increased in CD4(+) T cells isolated from patients with active systemic lupus erythematosus (SLE), especially in patients treated with glucocorticoid (GC). Increased expression of E4BP4 inhibited the activation and self-reactivity of T cells stimulated by anti-CD3/CD28 antibodies. In contrast, the self-reactivity was enhanced in CD4(+) T cells from SLE patients following E4BP4 gene silencing and the production of autoantibody was increased in autologous B cells. We further demonstrated that E4BP4 directly regulated CD40L expression by binding to the promoter region and altering histone acetylation and methylation of the CD40L loci. Taken together, our data provide evidence that E4BP4 can inhibit CD40L expression through epigenetic modifications in the promoter region of CD40L, thus negatively regulating self-reactivity of SLE CD4(+) T cells. Furthermore, our data demonstrate that overexpression of E4BP4 initiates a protective mechanism in SLE CD4(+) T cells, which may be a promising target in the therapy for SLE. PMID:23340290

  16. IRF1 marks activated genes in SLE and can induce target gene expression

    PubMed Central

    Zhang, Zhe; Shi, Lihua; Song, Li; Ephrem, Elshaddai; Petri, Michelle; Sullivan, Kathleen E.

    2014-01-01

    Objective IRF1 both mediates responses to type I interferons and the induction of interferons. It has been implicated in murine lupus models as a critical mediator of inflammation. A previous study of chromatin modifications in SLE patient monocytes implicated IRF1 as associated with increased histone acetylation in SLE patients. This study directly investigated IRF1 binding sites on chromatin using ChIP-seq. Methods Nine female SLE patients and seven female controls were examined. Monocytes were purified from peripheral blood and subjected to library preparation using a validated antibody to IRF1. The effect of IRF1 on target gene expression was confirmed using an overexpression system in cell lines and co-immunoprecipitation was used to define protein interactions. Results IRF1 binding around transcribed regions was increased in SLE patient monocytes but histone modifications at potential IRF1 binding sites without detectable IRF1 binding were also increased. IRF1 overexpression was sufficient to drive transcription of target genes. IRF1 overexpression was also able to alter histone modifications at a focus set of target genes and the use of an IRF1 inhibitor decreased both expression and histone modifications at target genes. IRF1 was found to interact with a select set of histone modifying enzymes and other transcription factors. Conclusions IRF1 is an important signaling protein in the interferon pathway. IRF1 not only activates gene expression as a transcription factor but may perpetuate disease by leading to a dysregulated epigenome. PMID:25418955

  17. Macrophages from patients with SLE and rheumatoid arthritis have defective adhesion in vitro, while only SLE macrophages have impaired uptake of apoptotic cells

    PubMed Central

    Tas, S W; Quartier, P; Botto, M; Fossati‐Jimack, L

    2006-01-01

    Background It has been suggested that defective handling of apoptotic cells by macrophages plays a key role in the development of systemic lupus erythematosus (SLE). The relative contribution of intrinsic defects and serum factors remains controversial. Objective To compare monocytes from SLE patients, patients with rheumatoid arthritis, and healthy controls for their ability to differentiate in vitro into macrophages and to bind/engulf apoptotic cells. Methods Peripheral blood derived monocytes from healthy donors or from patients with SLE or rheumatoid arthritis were allowed to differentiate into macrophages. The in vitro uptake of apoptotic cells by macrophages was evaluated by a flow cytometry assay that allowed discrimination between binding and internalisation. Results Monocytes from SLE and rheumatoid patients showed a striking defect in adherence to plastic compared with healthy donors. Absence or heat inactivation of serum resulted in a reduction in the binding and engulfment of apoptotic cells by macrophages. Macrophages from rheumatoid and SLE patients had similar percentages of apoptotic cells bound to their surface compared with normal controls. However, macrophages from SLE patients showed a significant defect in the internalisation of apoptotic cells compared with those from healthy controls, even in the presence of normal human serum. Conclusions Monocytes from patients with SLE and rheumatoid arthritis have a similar defect in their capacity to adhere to plastic. However, only macrophages from SLE patients showed an impaired ability to engulf apoptotic cells, which indicates that an intrinsic cellular defect may be responsible for this phenomenon. PMID:16014673

  18. Interleukin-1β (IL-1β) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE

    PubMed Central

    Mohammadoo-khorasani, Milad; Salimi, Saeedeh; Tabatabai, Ehsan; Sandoughi, Mahnaz; Zakeri, Zahra; Farajian-Mashhadi, Farzaneh

    2016-01-01

    Background & objectives: Interleukin-1 (IL-1) is one of the pro-inflammatory cytokines that plays a main role in the regulation of immune and inflammatory responses. Interleukin 4 (IL-4) as an anti-inflammatory cytokine regulates balance between Th1 and Th2 immune responses. This study was undertaken to investigate the IL-1β and IL-4 genes polymorphisms in patients with systemic lupus erythematosus (SLE) and also association between the polymorphisms and susceptibility to SLE. Methods: One hundred and sixty three SLE patients and 180 healthy controls were genotyped for the IL-4 VNTR (variable number tandem repeat), IL-1β C-511T and IL-1β T-31C polymorphisms by polymerase chain reaction (PCR) or PCR-RFLP (restriction fragment length polymorphism) method. Results: The frequencies of CC genotype and C allele of the IL-1β T-31C polymorphism were significantly (P<0.01) lower in SLE patients than controls. Moreover, the frequencies of RP1/RP2 genotype and RP2 allele of IL-4 VNTR polymorphism were significantly (P<0.05) higher in the SLE patients. No association was observed between IL-1β C-511T polymorphism and increased risk of SLE. We observed increased frequency of CT and TT genotypes of IL-1β C-511T polymorphism in SLE patients with malar rash compared to SLE patients without this manifestation. Interpretation & conclusions: The present findings suggest that IL-1β T-31C and IL-4 VNTR polymorphisms but not IL-1β C-511T polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes of IL-1β C-511T polymorphism were associated with SLE. PMID:27488002

  19. Recurrent laryngeal neuropathy in a systemic lupus erythematosus (SLE) patient.

    PubMed

    Lee, Jung Hwan; Sung, In Young; Park, Jin Hong; Roh, Jong-Lyel

    2008-01-01

    A 41-yr-old woman with hoarseness, multiple joint pain, and generalized myalgia was diagnosed with systemic lupus erythematosus (SLE) 7 mos before visiting our clinic. SLE-related vocal cord palsy of the left side was identified after otolaryngologic evaluation. We performed laryngeal electromyography (LEMG) on both cricothyroid and thyroarytenoid muscles. The findings indicated left recurrent laryngeal neuropathy with ongoing processes of denervation and reinnervation. Laryngeal involvement is a rare complication of SLE, but it is of clinical significance because serious consequence such as upper-airway obstruction can occur. LEMG identified this complication and precisely defined the neuromuscular status, and this information assisted in creating a therapeutic plan. LEMG may be useful for evaluating the neuromuscular status in vocal cord palsy. PMID:17993990

  20. Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE).

    PubMed Central

    Mitamura, K; Kang, H; Tomita, Y; Hashimoto, H; Sawada, S; Horie, T

    1991-01-01

    We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF-alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE. Images Fig. 2 PMID:1893618

  1. Extracellular signal-regulated kinase 1/2 signalling in SLE T cells is influenced by oestrogen and disease activity.

    PubMed

    Gorjestani, S; Rider, V; Kimler, B F; Greenwell, C; Abdou, N I

    2008-06-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs primarily in women of reproductive age. The disease is characterized by exaggerated T-cell activity and abnormal T-cell signalling. The mitogen-activated protein kinase (MAPK) pathway is involved in the maintenance of T-cell tolerance that fails in patients with SLE. Oestrogen is a female sex hormone that binds to nuclear receptors and alters the rate of gene transcription. Oestrogen can also act through the plasma membrane and rapidly stimulate second messengers including calcium flux and kinase activation. In this study, we investigated whether oestrogen influences the activation of MAPK signalling through the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in activated SLE T cells. SLE and control T cells were cultured in serum-free medium without and with oestradiol (10(-7) M) for 18 h. The T cells were activated with phorbol 12 myristate 13-acetate and ionomycin for various time points (0-60 min), and the amount of phosphorylated ERK1/2 was measured by immunoblotting. There were no differences in ERK1/2 phosphorylation between SLE and control T cells at 5 and 15 min after the activation stimulus. However, comparison between the amount of phosphorylated ERK1/2 in SLE T cells from the same patients cultured without and with oestradiol showed a significant oestrogen-dependent suppression (P=0.48) of ERK1/2 in patients with inactive/mild systemic lupus erythematosus disease activity index (SLEDAI) (0-2) compared with patients with moderate (4-6) or active (8-12) SLEDAI scores. These results suggest that the suppression of MAPK through ERK1/2 phosphorylation is sensitive to oestradiol in patients with inactive or mild disease, but the sensitivity is not maintained when disease activity increases. Furthermore, studies are now necessary to understand the mechanisms by which oestrogen influences MAPK activation in SLE T cells. PMID:18539708

  2. Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

    PubMed

    das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

    2016-04-01

    The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality. PMID:26405022

  3. Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort

    PubMed Central

    Lu, Rufei; Robertson, Julie M.; Bruner, Benjamin F.; Guthridge, Joel M.; Neas, Barbara R.; Nath, Swapan K.; Kelly, Jennifer A.; Moser Sivils, Kathy L.; Chakravarty, Eliza F.; Kamen, Diane L.; Gilkeson, Gary S.; Wallace, Daniel J.; Weisman, Michael H.; Scofield, R. Hal; Harley, John B.; James, Judith A.

    2012-01-01

    Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE) clinical features in a large lupus cohort. Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis. Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use. PMID:22988489

  4. An SLE patient with prolactinoma and recurrent granulomatous mastitis successfully treated with hydroxychloroquine and bromocriptine.

    PubMed

    Zhang, L-N; Shi, T-Y; Yang, Y-J; Zhang, F-C

    2014-04-01

    Granulomatous mastitis (GM) is a rare benign mammary lesion in which autoimmunity and hyperprolactinemia are considered possible etiological factors. GM has a high frequency of relapse and may lead to chronic ulceration and fistula if not treated properly. Here we report a case of a 22-year-old systemic lupus erythematosus (SLE) patient with three years' disease duration, stable on prednisone and hydroxychloroquine, who was found to have prolactinoma and recurrent GM after she discontinued medication on her own accord. The patient subsequently recovered and remained free of GM relapse under treatment of prednisone, hydroxychloroquine and bromocriptine. Though autoimmune disorders and prolactinoma were reported in GM, a coexisting condition of SLE, prolactinoma, and granulomatous mastitis has rarely been observed in one patient. We suggest our case as an illustrative example of the complex interaction between autoimmunity, neuroendocrine dysfunction, and manifestations in the breast: Immunological disturbances in the background of SLE, coupled with elevated prolactin levels secondary to a prolactinoma, may have predisposed the patient to the development of GM. The mammary lesion recovered and maintained free of relapse under immunosuppressive and antiprolactinemic therapy. PMID:24446305

  5. Increased expression of TLR2 in CD4(+) T cells from SLE patients enhances immune reactivity and promotes IL-17 expression through histone modifications.

    PubMed

    Liu, Yu; Liao, Jieyue; Zhao, Ming; Wu, Haijing; Yung, Susan; Chan, Tak Mao; Yoshimura, Akihiko; Lu, Qianjin

    2015-09-01

    The innate immune system has been shown to play an important pathologic role in systemic lupus erythematosus (SLE). TLR2, a PRR, recognizes exogenous PAMPs, and endogenous damage-associated molecular patterns and has been implicated in the initiation and maintenance of the perpetuated inflammatory reactions in autoimmune diseases. Here, we report increased expression of TLR2 in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes from SLE patients. Conventional treatment, such as hydroxychloroquine and corticosteroids, showed no effect on TLR2 expression in CD4(+) T cells from SLE patients. In vitro stimulation of TLR2 in CD4(+) T cells from SLE patients increased CD40L and CD70 expression, as well as secretion of IL-6, IL-17A, IL-17F, and TNF-α, while Foxp3 transcription decreased. This effect was reversed by TLR2 siRNA. Moreover, TLR2 activation upregulated H3K4 tri-methylation and H4 acetylation levels while downregulated H3K9 tri-methylation level in the IL-17A promoter region. In addition, it also increased H4 acetylation levels and decreased H3K9 tri-methylation levels in the IL-17F promoter region. In summary, our findings demonstrate that increased expression of TLR2 contributes to immune reactivity and promotes IL-17A and IL-17F expression through histone modifications in SLE. PMID:26079624

  6. Autoantibodies to purified nuclear proteins related to DNA metabolism during ageing and in SLE patients.

    PubMed Central

    Astaldi Ricotti, G C; Pazzaglia, M; Martelli, A M; Cerino, A; Bestagno, M; Caprelli, A; Riva, S; Pedrini, M A; Facchini, A

    1987-01-01

    In this study the specificity of circulating autoantibodies in ANA+ aged donors, ANA- donors and SLE patients was investigated by immunoblotting on total nuclear proteins and by ELISA on purified nuclear proteins, possibly related to DNA metabolism, such as DNA polymerase alpha, DNA-dependent ATPase, DNA Topoisomerase I, ssDBP, hnRNP, HMG and histones. Immunoblotting showed that sera from ANA+ aged donors present fewer antibodies to nuclear proteins, especially to those between 21,000 and 45,000, molecular weight (MW), than sera from SLE patients. When the specificity of antisera was further studied on purified nuclear proteins, it was found that the majority of sera from SLE patients react with most of the proteins tested, whereas sera from ANA+ aged donors mainly react with DNA polymerase alpha, DNA-dependent ATPase, DNA Topoisomerase I and histones. In addition, sera from a few ANA- donors also reacted with certain purified nuclear proteins in a statistically significant age-related manner. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3497092

  7. Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial)

    PubMed Central

    Isenberg, David; Gordon, Caroline; Licu, Daiana; Copt, Samuel; Rossi, Claudia Pena; Wofsy, David

    2015-01-01

    Objectives Despite advances in systemic lupus erythematosus (SLE) treatment, many patients suffer from the disease and side effects. Atacicept is a fusion protein that blocks B-lymphocyte stimulator and a proliferation-inducing ligand, which are increased in patients with SLE. Methods In this double-blind, placebo-controlled study, patients with moderate-to-severe SLE were randomised to atacicept 75 mg or atacicept 150 mg administered subcutaneously, or placebo twice-weekly for 4 weeks, then weekly for 48 weeks. Primary and secondary efficacy measures were the proportion of patients experiencing at least one flare of British Isles Lupus Assessment Group A or B, and time to first flare, respectively. Results Enrolment in the atacicept 150 mg arm was discontinued prematurely due to two deaths. In the intention-to-treat population (n=461), there was no difference in flare rates or time to first flare between atacicept 75 mg and placebo. Analysis of patients treated with atacicept 150 mg suggested beneficial effect versus placebo in flare rates (OR: 0.48, p=0.002) and time to first flare (HR: 0.56, p=0.009). Both atacicept doses were associated with reductions in total Ig levels and anti-dsDNA antibodies, and increases in C3 and C4 levels. Most treatment-emergent adverse events were mild or moderate. Conclusions There was no difference between atacicept 75 mg and placebo for flare rate or time to first flare. Analysis of atacicept 150 mg suggested benefit. Trial registration number EudraCT: 2007-003698-13; NCT00624338. PMID:24951103

  8. Quality of life in patients with systemic lupus erythematosus (SLE) compared with related controls within a unique African American population

    PubMed Central

    Barnado, A; Wheless, L; Meyer, AK; Gilkeson, GS; Kamen, DL

    2012-01-01

    The patient’s perspective of how their health affects their function is health-related quality of life (HRQOL). HRQOL is poorer in patients with systemic lupus erythematosus (SLE). Few HRQOL studies in SLE patients have focused on African Americans despite an increased disease burden compared with Caucasians. The African American Gullah population of South Carolina has a homogeneous genetic and environmental background and a high prevalence of multi-patient families with SLE. Demographics, medical history, and Short-Form 36 (SF-36) were measured within a cohort of Gullah SLE cases and related controls. Compared with related controls (n = 37), cases (n = 89) had a lower Physical Component Summary (PCS, 41.8 vs. 52.3, p < 0.01), but not Mental Component Summary (MCS, 55.0 vs. 56.0, p = 0.70). The difference in PCS was no longer significant upon adjustment for working status, disability, and medical conditions. None of the 11 SLE American College of Rheumatology criteria, disease duration, or Systemic Lupus International Collaborating Clinics Damage Index were associated with either PCS or MCS. Cases and controls had similar MCS scores. We hypothesize that this lack of effect of SLE on MCS may be due to disease-coping mechanisms interplaying with cultural factors unique to the Gullah. PMID:22031537

  9. Standard medical care of patients with systemic lupus erythematosus (SLE) in large specialised centres: data from the Russian Federation, Ukraine and Republic of Kazakhstan (ESSENCE)

    PubMed Central

    Nasonov, E; Soloviev, S; Davidson, J E; Lila, A; Togizbayev, G; Ivanova, R; Baimukhamedov, Ch; Omarbekova, Zh; Iaremenko, O; Gnylorybov, A; Shevchuk, S; Vasylyev, A; Pereira, M H S

    2015-01-01

    Objectives To describe disease characteristics and treatment regimens for adult patients with systemic lupus erythematosus (SLE) with autoantibody positive disease in three countries (the Russian Federation, Ukraine and Republic of Kazakhstan). Methods The ESSENCE study was a 1-year, retrospective, multicentre, observational study. Data included patients’ characteristics, disease activity and severity, and healthcare resource use in 2010. Results Twelve centres enrolled 436 eligible patients: 232 in Russia, 110 in Kazakhstan and 94 in Ukraine. Mean age ranged from 36 to 42 years and median SLE duration from 3 to 6.8 years. According to study definitions, 69.2% of patients in Russia, 72.7% in Kazakhstan and 55.4% in Ukraine had severe disease at diagnosis. SLE activity (Nasonova classification, 1972) decreased from diagnosis to the last visit in 2010 in all countries. At the last visit, mean (SD) Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index score was 13.8 (10.5) in Russia, 19.4 (16.9) in Kazakhstan and 7.2 (6.8) in Ukraine, and Systemic Lupus International Collaborative Clinics/American College of Rheumatology damage index was 2.0 (2.2), 3.3 (3.2) and 2.2 (2.0), respectively. Treatment regimens included predominantly glucocorticoids (96.7–99.1%), immunosuppressants or cytotoxic drugs, for example, azathioprine and cyclophosphamide (20.7–53.2%), and antimalarial drugs (18.3–40.8%). Conclusions The study provides reliable insight into the SLE clinical profiles in the referenced countries. Patients were 4–10 years younger in the study and had 3–7 years shorter SLE duration than in Western European countries and both SLE activity and severity were higher with higher rate of hospitalisations, but decreased during treatment. Local and international scales demonstrated correlation in SLE activity and organ damage evaluation. There were differences in clinical characteristics and

  10. Exploring lifetime occupational exposure and SLE flare: a patient-focussed pilot study

    PubMed Central

    Squance, Marline L; Guest, Maya; Reeves, Glenn; Attia, John; Bridgman, Howard

    2014-01-01

    Introduction Environmental effectors, such as ultraviolet radiation exposure, infection and stress, have been established as having a role in exacerbating lupus symptoms. However, unpredictable patterns of flare events still remain a mystery. Occupational effectors have also been suggested as having a contributing role; however, they are not widely researched. In this paper we report a pilot study designed to generate focus areas for future research regarding occupational exposures and systemic lupus erythematosus (SLE). Methods The study explored potential links between exposures and the occurrence of patient-reported flare events in 80 Australian women with SLE (American College of Rheumatology (ACR) criteria classified). Specifically, the study assessed the hypothesis that occupational exposure is associated with significant changes in the likelihood of lupus flares. Lifetime employment history was analysed with the Finnish Job Exposure Matrix (FINJEM), 40 different semiquantified exposure class estimates for a wide number of occupations based on probability of exposure (p≥5%=exposed) were analysed with the construction of negative binomial regression models to test relationships between occupational agents and flare days. A backward stepwise elimination was used to generate a parsimonious model. Results Significant associations were noted for exposure classes of manual handling burden, (p=0.02, incidence rate ratio (IRR) 1.01), Iron (p=0.00, IRR 1.37), wood dust (p=0.00, IRR 3.34) and asbestos (p=0.03, IRR 2.48). Conclusion Exposure assessment results indicated that occupations, such as nursing, with a high manual handling burden, posed increased risk to patients with SLE, however, the greatest risk was associated with wood dust and iron exposure with teachers and specialist labourers. PMID:25379190

  11. In a SLE mouse model the production of IgG autoantibody requires expression of activation-induced deaminase in early developing B cells

    PubMed Central

    Umiker, Benjamin R.; McDonald, Gabrielle; Larbi, Amma; Medina, Carlos O.; Reth, Michael; Imanishi-Kari, Thereza

    2014-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of pathogenic IgG anti-nuclear antibodies. Pathogenic IgG autoantibody production requires B-cell activation, leading to the production of activation-induced deaminase (AID) and class switching of IgM genes to IgG. To understand how and when B cells are activated to produce these IgG autoantibodies, we studied cells from 564Igi, a mouse model of SLE. 564Igi mice develop a disease profile closely resembling that found in human SLE patients, including the presence of IgG anti-nucleic acid antibodies. We have generated 564Igi mice that conditionally express an activation-induced cytidine deaminase transgene (Aicdatg), either in all B cells or only in mature B cells. Here we show that class-switched pathogenic IgG autoantibodies were produced only in 564Igi mice in which AID was functional in early developing B cells, resulting in loss of tolerance. Furthermore, we show that the absence of AID in early developing B cells also results in increased production of self-reactive IgM, indicating that AID, through somatic hypermutation (SHM), contributes to tolerance. Our results suggest that the pathophysiology of clinical SLE might also be dependent on AID expression in early developing B cells. PMID:25044405

  12. Fertility, ovarian failure, and pregnancy outcome in SLE patients treated with intravenous cyclophosphamide in Saudi Arabia.

    PubMed

    Alarfaj, Abdurhman Saud; Khalil, Najma

    2014-12-01

    Intravenous cyclophosphamide (IV CYC) has been and still used for treatment of severe manifestations of systemic lupus erythematosus (SLE), a disease occurring predominantly in women. IV CYC has been shown to predispose patients to ovarian failure and adverse pregnancy outcomes. We studied the impact of prior IV CYC treatment on ovarian function and pregnancy in our SLE patients, in terms of amenorrhea, fertility, and pregnancy outcome over a 26-year period. The study included 535 women (319 married), out of which 188 received IV CYC and 347 did not. Sixty-one patients experienced amenorrhea; the rate of amenorrhea in IV CYC user group (28.2 %; n = 53) was significantly higher than that in non-IV CYC group (3.7 %; n = 8) (P < 0.05). The type of amenorrhea was assessed in 99 women receiving IV CYC. Thirty-four (34.3 %) of them developed amenorrhea which was transient in 21 (21.2 %) and sustained in 13 (13.1 %) women. The older age at the time of receiving IV CYC and its higher cumulative dose were found to be risk factors for amenorrhea. Among married women, 48 of 99 (48.5 %) in IV CYC group conceived 90 pregnancies and 128 of 220 (58.2 %) in non-IV CYC group conceived 293 pregnancies. The rates of abortions, fetal loss, and live births between the two groups were similar; however, women with prior IV CYC had significantly more preterm births. Prior IV CYC was no barrier to conception; pregnancy outcome was favorable but associated with amenorrhea and preterm deliveries. PMID:24894105

  13. IL-10 and TNFα Genotypes in SLE

    PubMed Central

    López, Patricia; Gutiérrez, Carmen; Suárez, Ana

    2010-01-01

    The production of two regulators of the inflammatory response, interleukin 10 (IL-10) and tumor necrosis factor α (TNFα), has been found to be deeply deregulated in SLE patients, suggesting that these cytokines may be involved in the pathogenesis of the disease. Genetic polymorphisms at the promoter regions of IL-10 and TNFα genes have been associated with different constitutive and induced cytokine production. Given that individual steady-state levels of these molecules may deviate an initial immune response towards different forms of lymphocyte activation, functional genetic variants in their promoters could influence the development of SLE. The present review summarizes the information previously reported about the involvement of IL-10 and TNFα genetic variants on SLE appearance, clinical phenotype, and outcome. We show that, in spite of the heterogeneity of the populations studied, the existing knowledge points towards a relevant role of IL-10 and TNFα genotypes in SLE. PMID:20625422

  14. Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies.

    PubMed

    Jucaud, V; Ravindranath, M H; Terasaki, P I; Morales-Buenrostro, L E; Hiepe, F; Rose, T; Biesen, R

    2016-03-01

    T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over-expression of human leucocyte antigen (HLA)-Ib on the surface of lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA-Ib (HLA-E, HLA-F and HLA-G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA-Ib and β2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex(®)-based flow cytometry. The values were expressed as mean flourescence intensity (MFI). Only the German SLE cohort was analysed in relation to the clinical disease activity. In the controls, anti-HLA-G IgG predominated over other HLA-Ib antibodies, whereas SLE patients had a preponderance of anti-HLA-F IgG over the other HLA-Ib antibodies. The disease activity index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000, was reflected only in the levels of anti-HLA-F IgG. Anti-HLA-F IgG with MFI level of 500-1999 was associated with active SLE, whereas inactive SLE revealed higher MFI (>2000). When anti-HLA-F IgG were cross-reactive with other HLA-Ib alleles, their reactivity was reflected in the levels of anti-HLA-E and -G IgG. The prevalence of HLA-F-monospecific antibodies in SLE patients was also associated with the clinical disease activity. Anti-HLA-F IgG is possibly involved in the clearance of HLA-F shed from lymphocytes and inflamed tissues to lessen the disease's severity, and thus emerges as a beneficial immune biomarker. Therefore, anti-HLA-Ib IgG should be considered as a biomarker in standard SLE diagnostics. PMID:26440212

  15. Murine lupus susceptibility locus Sle1c2 mediates CD4+ T cell activation and maps to estrogen-related receptor γ.

    PubMed

    Perry, Daniel J; Yin, Yiming; Telarico, Tiffany; Baker, Henry V; Dozmorov, Igor; Perl, Andras; Morel, Laurence

    2012-07-15

    Sle1c is a sublocus of the NZM2410-derived Sle1 major lupus susceptibility locus. We have shown previously that Sle1c contributes to lupus pathogenesis by conferring increased CD4(+) T cell activation and increased susceptibility to chronic graft-versus-host disease (cGVHD), which mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675-kb interval, termed Sle1c2. Mice from recombinant congenic strains expressing Sle1c2 exhibited increased CD4(+) T cell intrinsic activation and cGVHD susceptibility, similar to mice with the parental Sle1c. In addition, B6.Sle1c2 mice displayed a robust expansion of IFN-γ-expressing T cells. NZB complementation studies showed that Sle1c2 expression exacerbated B cell activation, autoantibody production, and renal pathology, verifying that Sle1c2 contributes to lupus pathogenesis. The Sle1c2 interval contains two genes, only one of which, Esrrg, is expressed in T cells. B6.Sle1c2 CD4(+) T cells expressed less Esrrg than B6 CD4(+) T cells, and Esrrg expression was correlated negatively with CD4(+) T cell activation. Esrrg encodes an orphan nuclear receptor that regulates oxidative metabolism and mitochondrial functions. In accordance with reduced Esrrg expression, B6.Sle1c2 CD4(+) T cells present reduced mitochondrial mass and altered mitochondrial functions as well as altered metabolic pathway utilization when compared with B6 CD4(+) T cells. Taken together, we propose Esrrg as a novel lupus susceptibility gene regulating CD4(+) T cell function through their mitochondrial metabolism. PMID:22711888

  16. Murine Lupus Susceptibility Locus Sle1c2 Mediates CD4+ T cell Activation and Maps to Estrogen-Related Receptor Gamma Esrrg

    PubMed Central

    Perry, Daniel J.; Yin, Yiming; Telarico, Tiffany; Baker, Henry V.; Dozmorov, Igor; Perl, Andras; Morel, Laurence

    2012-01-01

    Sle1c is a sublocus of the NZM2410-derived Sle1 major lupus susceptibility locus. We have previously shown that Sle1c contributes to lupus pathogenesis by conferring increased CD4+ T cell activation and increased susceptibility to chronic graft-versus-host disease (cGVHD), which mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675Kb interval, termed Sle1c2. Mice from recombinant congenic strains expressing Sle1c2 exhibited increased CD4+ T cell intrinsic activation and cGVHD susceptibility, similar to mice with the parental Sle1c. In addition, B6.Sle1c2 mice displayed a robust expansion of IFNγ expressing T cells. NZB complementation studies showed that Sle1c2 expression exacerbated B cell activation, autoAb production, and renal pathology, verifying that Sle1c2 contributes to lupus pathogenesis. The Sle1c2 interval contains two genes, only one of which, Esrrg, is expressed in T cells. B6.Sle1c2 CD4+ T cells expressed less Esrrg than B6 CD4+ T cells, and Esrrg expression was negatively correlated to CD4+ T cell activation. Esrrg encodes for an orphan nuclear receptor that regulates oxidative metabolism and mitochondrial functions. In accordance with a reduced Esrrg expression, B6.Sle1c2 CD4+ T cells present reduced mitochondrial mass and altered mitochondrial functions, as well as altered metabolic pathway utilization when compared to B6. Taken together, we propose Esrrg as a novel lupus susceptibility gene regulating CD4+ T cell function through their mitochondrial metabolism. PMID:22711888

  17. Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study.

    PubMed Central

    Spronk, P E; Bootsma, H; Huitema, M G; Limburg, P C; Kallenberg, C G

    1994-01-01

    Active SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI), and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (P < 0.0001), levels in patients with renal involvement being higher than in those without (P < 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P < 0.05) and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-1 were higher at the moment of relapse (P = 0.001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-1 are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial

  18. Silent Burdens in Disease: Fatigue and Depression in SLE

    PubMed Central

    Fonseca, R.; Bernardes, M.; Terroso, G.; de Sousa, M.; Figueiredo-Braga, M.

    2014-01-01

    At a time when health is being recognized as more than just avoiding death, age and comorbidity are becoming increasingly important aspects of chronic disease. Systemic Lupus Erythematous (SLE) is probably one of the best paradigms of modern chronic disease, sitting at the crossroads of numerous somatic health problems, immune activation, depression, pain, and fatigue. One hundred forty-eight female participants were enrolled in the present study: 50 diagnosed with SLE, 45 with major depressive disorder (MDD), and 53 age-matched controls. Statistically significant lower scores in quality-of-life dimensions related to physical impairment were found in SLE. Patients with MDD presented significant levels of pain, reduced physical summary component (PSC), and general health scores different from healthy controls. Fatigue was reported in 90% of women with SLE and 77.8% of the MDD patients in contrast with 39.6% in the control group. Significant correlations were seen among fatigue severity, age, and educational level in SLE. From our own previous work and more recent work on the association of immune activation and depression, unexplained fatigue in SLE may signify an early sign of immune activation flare-up. The search for cytokine markers should perhaps be extended to fatigue in SLE. PMID:24592329

  19. Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in SLE patients: glycated-histones as likely trigger for SLE?

    PubMed

    Alam, Sana; Arif, Zarina; Alam, Khursheed

    2015-02-01

    Histones are the most abundant proteins associated with genomic DNA. Recent observations show that histones are quite susceptible to non-enzymatic glycation which results in the generation of free radicals causing structural perturbations. In this study, our aim is to define the role of deoxyribose-modified H2A histone in SLE initiation/progression. Glycation reaction was carried out by incubating H2A histone with 10 mM deoxyribose for 21 days at 37 °C. Structural changes in glycated-H2A were studied by various physico-chemical techniques. The antigen-antibody interaction was studied by direct binding, inhibition ELISA and mobility shift assay. Deoxyribose-modified-H2A histone showed increased hyperchromicity and increased fluorescence intensity. CD results demonstrated almost 50% loss in alpha helix conformation as a consequence of glycation. This was supported by an increase in Tm value vis-à-vis thermal stability. Glycated-H2A showed cross linking in SDS-PAGE. SLE sera positive for anti-nDNA autoantibodies showed preference for deoxyribose-modified-H2A histone compared to native H2A histone or native DNA. Inhibition ELISA supported the above findings. Band shift assay further reiterated the preferential recognition of glycated-H2A over native H2A by SLE IgG autoantibodies. Deoxyribose-modified-H2A histone exhibited damage as revealed by various physico-chemical studies. Glycation of H2A has resulted in the generation of neo-epitopes on H2A histone, which are preferably bound by SLE anti-nDNA autoantibodies. It implies that deoxyribose-modified-H2A may trigger immune response resulting in the generation of anti-glycated H2A antibodies with DNA cross reacting properties. PMID:25065453

  20. Association of γδ T Cell Compartment Size to Disease Activity and Response to Therapy in SLE

    PubMed Central

    Ma, Hongshuang; Yuan, Yi; Zhao, Ling; Ye, Zhuang; Xu, Jiandong; Li, Man; Jiang, Zhenyu; Jiang, Yanfang

    2016-01-01

    Objective Although γδT cells are widely recognized as pivotal elements in immune-mediated diseases, their role in the pathogenesis of SLE and therapeutic outcome remains under explored. The current study aims to characterize the γδT cell compartment in SLE and correlate its status to disease severity and response to therapy. Methods Human peripheral blood-derived γδ T cells were isolated from 14 healthy volunteers and 22 SLE patients (before and after 4 and 12 weeks following the onset of glucocorticoids (GC), mycophenolatemofetil (MMF) orhydroxychloroquine (HCQ) treatment). The γδ T cells were characterized using flow cytometry. In addition, serum concentration of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A was determined by cytometric bead array (CBA). Results The SLEDAI scores dropped significantly following therapy in a subset of patients (responders–R) but not in some (non- responders–NR). Peripheral blood γδ T cells in general, and γ9+δ T cells and TNF-α/IL-17-secreting CD4-CD8-γδ T cell subsets in particular, were decreased in SLE compared to healthy controls. The numbers of the γδ T cell subsets reached levels similar to those of healthy controls following therapy in R but not in NR. Serum IL-6, IL-10 and IL-17 but not IFN-γ and TNF-α were significantly increased in SLE compared to the healthy controls and exhibited differential changes following therapy. In addition, inverse correlation was observed between SLEDAI scores and γδ T cell compartments, especially with TNF-α+γδT cells, TNF-α+γ9+δT cells and IL17+CD4-CD8-γδT cells subsets. Differential correlation patterns were also observed between serum cytokine levels and various γδ T cell compartments. Conclusions A strong association exists between γδ T cell compartments and SLE pathogenesis, disease severity and response to therapy. PMID:27333282

  1. Effects of red blood cell lysing solutions on the detection of peripheral basophils of healthy normals and SLE patients by flow cytometry.

    PubMed

    Pan, Qingjun; Ye, Ling; Deng, Zhenzhen; Li, Lu; Liu, Huafeng

    2014-01-01

    To evaluate the effect of four widely used red blood cell lysing solutions on counting and measurement of activation marker of peripheral basophils in normals and systemic lupus erythematosus (SLE) patients by flow cytometry. Our results showed that the light scatter properties including FS and SS value of leukocytes in whole blood were preserved when whole blood samples were lysed in RBC Lysis Buffer and FACS Lysing Solution, while were affected when lysed in distilled water or ACK. By counting basophils, RBC Lysis Buffer and FACS Lysing Solution were almost the same level, while were significantly lower when lysed in distilled water or ACK. The expressions of CD203c on peripheral basophils of SLE patients were significantly higher than those of normals. Comparing the data of CD203c expression obtained demonstrated that there were no significant differences among them, while FACS Lysing Solution treatment leads to a slightly lower staining intensity of CD203c. We provide a solid description that the widely used red blood cell lysing reagents may influence the light scatter properties of leukocytes, the accuracy of quantity of absolute number of the existence of basophil subsets and the quantity of staining intensity of cell-activated marker CD203c fluorescence when measured by flow cytometry. PMID:24593031

  2. Prevalence and correlates of suicidal ideation in SLE inpatients: Chinese experience.

    PubMed

    Xie, Lun-Fang; Chen, Pei-Ling; Pan, Hai-Feng; Tao, Jin-Hui; Li, Xiang-Pei; Zhang, Yu-Jing; Zhai, Yu; Ye, Dong-Qing

    2012-09-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Because of double damages of body and mind, SLE patients are in a potential risk of suicide. Many factors may contribute to the occurrence of suicide in SLE: socioeconomic factors, medical factors, mental health, family support and coping style. This study aims to investigate the prevalence and correlates of suicidal ideation in SLE inpatients in China in order to determine whether they had risk of suicide, and if so, what factors should be paid more attention to prevent suicide in wards. A total of 285 SLE patients were interviewed with questionnaires on suicidal ideation and socio-demographic characteristics, Beck Depression Inventory (BDI), Family APGAR and Trait Coping Style Questionnaire (TCSQ). Disease activity was assessed with SLE Disease Activity Index. The other medical information was collected from the patients' medical records. In total, 34.4% of SLE patients had current suicidal ideation. Significant individual risk factors for current suicidal ideation in SLE patients included having religious belief, heavy self-reported financial burdens, long duration of SLE, low level of family functioning and negative coping style. And in the presence of these risk factors, being separated, divorced or widowed, having premorbid suicidal ideation and depression were independent predictors of suicidal ideation. In summary, the rate of suicidal ideation in SLE patients in China is higher than that in other countries. Factors that contribute to risk of suicidal ideation include social and cultural domains and physical and psychological health. Although the association of suicidal ideation to religions and medical factors is still to be investigated, these findings may give some references to suicide prevention efforts for SLE patients in China. PMID:21792644

  3. Chinese SLE treatment and research group registry: III. association of autoantibodies with clinical manifestations in Chinese patients with systemic lupus erythematosus.

    PubMed

    Li, Jing; Leng, Xiaomei; Li, Zhijun; Ye, Zhizhong; Li, Caifeng; Li, Xiaofeng; Zhu, Ping; Wang, Zhengang; Zheng, Yi; Li, Xiangpei; Zhang, Miaojia; Tian, Xin-Ping; Li, Mengtao; Zhao, Jiuliang; Zhang, Feng-Chun; Zhao, Yan; Zeng, Xiaofeng

    2014-01-01

    We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P<0.05) associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P<0.05). Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P<0.05). Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed. PMID:24864270

  4. Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of SLE patients and family members

    PubMed Central

    Bruner, Benjamin F.; Guthridge, Joel M.; Lu, Rufei; Vidal, Gabriel; Kelly, Jennifer A.; Robertson, Julie M.; Kamen, Diane L.; Gilkeson, Gary S.; Neas, Barbara R.; Reichlin, Morris; Scofield, R. Hal; Harley, John B.; James, Judith A.

    2012-01-01

    Objective The replacement of standard immunofluorescence anti-nuclear antibody (ANA) methods with bead-based assays is a new clinical option. A large, multi-racial cohort of SLE patients, blood relatives and unaffected control individuals was evaluated for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. Methods Serum samples (1,540 SLE patients, 1,127 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, immunofluorescence, and immunodiffusion. Autoantibody prevalence, disease sensitivity, clustering, and association with standard immunodiffusion results were evaluated. Results ANA frequency in SLE patient sera were 89%, 73%, and 67% by BioPlex 2200 and 94%, 84%, and 86% by immunofluorescence in African-American, Hispanic, and European-American patients respectively. 60kD Ro, La, Sm, nRNP A, and ribosomal P prevalence were compared across assays, with sensitivities ranging from 0.92 to 0.83 and specificities ranging from 0.90 to 0.79. Cluster autoantibody analysis showed association of three subsets: 1) 60kD Ro, 52kD Ro and La, 2) spliceosomal proteins, and 3) dsDNA, chromatin, and ribosomal P. Familial aggregation of Sm/RNP, ribosomal P, and 60kD Ro in SLE patient sibling pairs was observed (p ≤ 0.004). Simplex pedigree patients had a greater prevalence for dsDNA (p=0.0003) and chromatin (p=0.005) autoantibodies than multiplex patients. Conclusion ANA frequencies detected by a bead-based assay are lower in European-American SLE patients compared to immunofluorescence. These assays have strong positive predictive values across racial groups, provide useful information for clinical care, and provide unique insights to familial aggregation and autoantibody clustering. PMID:23112091

  5. A Multilocus Genetic Study in a Cohort of Italian SLE Patients Confirms the Association with STAT4 Gene and Describes a New Association with HCP5 Gene

    PubMed Central

    Ciccacci, Cinzia; Perricone, Carlo; Ceccarelli, Fulvia; Rufini, Sara; Di Fusco, Davide; Alessandri, Cristiano; Spinelli, Francesca Romana; Cipriano, Enrica; Novelli, Giuseppe; Valesini, Guido

    2014-01-01

    Background Systemic lupus erythematosus (SLE) is an autoimmune disease with complex pathogenesis in which genes and environmental factors are involved. We aimed at analyzing previously identified loci associated with SLE or with other autoimmune and/or inflammatory disorders (STAT4, IL10, IL23R, IRAK1, PSORS1C1, HCP5, MIR146a, PTPN2, ERAP1, ATG16L1, IRGM) in a sample of Italian SLE patients in order to verify or confirm their possible involvement and relative contribution in the disease. Materials and methods Two hundred thirty-nine consecutive SLE patients and 278 matched healthy controls were enrolled. Study protocol included complete physical examination, and clinical and laboratory data collection. Nineteen polymorphisms were genotyped by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed. Results STAT4 was the most associated gene [P = 3×10−7, OR = 2.13 (95% CI: 1.59–2.85)]. IL10 confirmed its association with SLE [rs3024505: P = 0.02, OR = 1.52 (95% CI: 1.07–2.16)]. We describe a novel significant association between HCP5 locus and SLE susceptibility [rs3099844: P = 0.01, OR = 2.06 (95% CI: 1.18–3.6)]. The genotype/phenotype correlation analysis showed several associations including a higher risk to develop pericarditis with STAT4, and an association between HCP5 rs3099844 and anti-Ro/SSA antibodies. Conclusions STAT4 and IL10 confirm their association with SLE. We found that some SNPs in PSORS1C1, ATG16L1, IL23R, PTPN2 and MIR146a genes can determine particular disease phenotypes. HCP5 rs3099844 is associated with SLE and with anti-Ro/SSA. This polymorphism has been previously found associated with cardiac manifestations of SLE, a condition related with anti-Ro/SSA antibodies. Thus, our results may provide new insights into SLE pathogenesis. PMID:25369137

  6. Defects in Germinal Center Selection in SLE

    PubMed Central

    Woods, Megan; Zou, Yong-Rui; Davidson, Anne

    2015-01-01

    Germinal centers (GCs) are the primary site at which clonal expansion and affinity maturation of B cells occur. B cells encounter antigen and receive T cell help in the GC light zone (LZ) and then migrate to the dark zone where they proliferate and undergo somatic mutation before cycling back to the LZ for further rounds of selection. Tolerance to autoantigens is frequently lost de novo as GC B cells undergo class switching and somatic mutation. This loss of tolerance is regulated by a variety of mechanisms including cell death, failure to compete for T cell help, and failure to differentiate into effector cells. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance to nucleic acid antigens. While defects in tolerance occur in the naïve repertoire of SLE patients, pathogenic autoantibodies also arise in the GC by somatic mutation from non-autoreactive precursors. Several B cell defects contribute to the loss of GC tolerance in SLE, including polymorphisms of genes encoded by the Sle1 locus, excess TLR7 signaling, defects in FcRIIB expression, or defects of B cell apoptosis. Extrinsic soluble factors, such as Type-1 IFN and B cell-activating factor, or an increased number of T follicular helper cells in the GC also alter B cell-negative selection. Finally, defects in clearance of apoptotic debris within the GC result in BCR-mediated internalization of nucleic acid containing material and stimulation of autoantibody production by endosomal TLR-driven mechanisms. PMID:26322049

  7. The rate of loss of CR1 from ageing erythrocytes in vivo in normal subjects and SLE patients: no correlation with structural or numerical polymorphisms.

    PubMed Central

    Moldenhauer, F; Botto, M; Walport, M J

    1988-01-01

    The stability of CR1 (complement receptor type 1) on ageing erythrocytes in vivo was examined in a group of normal subjects who had been genotyped using a restriction fragment length polymorphism (detected using a cDNA probe for CR1) that correlates with the numerical expression of CR1 on normal erythrocytes (H = allele correlating with high expression, L = low). Erythrocytes were separated into 5 fractions of increasing age on discontinuous Percoll gradients. Mean CR1 numbers on erythrocytes fell from 636 molecules per cell in the first fraction to 384 in the fifth in the HH group and from 478 to 315 in the LL group. There was no difference in the rate of decline of CR1 numbers between the groups. A group of nine SLE patients was also studied in the same way; their genotypes were HH (four) and HL (five). Mean CR1 numbers amongst all of these patients fell from 477 to 232, a faster rate of decline than in a genotypically matched group of normal subjects. There was no difference in the prevalence of the different structural allotypes amongst 30 SLE patients compared with 21 normal subjects. These data provide further evidence that there are enhanced extracellular mechanisms for the removal of CR1 from erythrocytes of SLE patients and do not support the hypothesis that inherited variation in CR1 expression on erythrocytes increases disease susceptibility to SLE. PMID:2899464

  8. Immune cells and type 1 IFN in urine of SLE patients correlate with immunopathology in the kidney.

    PubMed

    Scott, Eric; Dooley, Mary Anne; Vilen, Barbara J; Clarke, Stephen H

    2016-07-01

    The immunopathological events in the kidneys of lupus nephritis (LN) patients are poorly understood due in part to the difficulty in acquiring serial biopsies and the inherent limitations in their analysis. To identify a means to circumvent these limitations, we investigated whether immune cells of kidney origin are present in patient urine and whether they correlate with kidney pathology. Flow cytometry analysis was performed on peripheral blood and urine cells of 69 SLE patients, of whom 41 were LN patients. In addition, type I IFN (IFNα/β) levels were determined in plasma and urine by bioassay. Approximately 60% of non-LN patients had urine lymphocytes. In these patients, T cells were always present and predominantly CD8(+), while B cells were either absent or a mixture of naïve and memory B cells. In contrast, >90% of LN patients had urine lymphocytes. In half, the B and T cells resembled those in non-LN patient urine; however, in the remaining patients, the B cells were exclusively Ig-secreting plasmablasts or plasma cells (PB/PCs) and the T cells were predominantly CD4(+). In addition, pDCs and IFNα/β frequently accompanied PB/PCs. The majority of patients with urine PB/PCs presented with proliferative nephritis and a significant loss of kidney function, which in some cases had progressed to end stage renal disease (ESRD). In conclusion, urine can provide access to cells of kidney resident populations for phenotypic and functional characterization. Analysis of these cells provides insight into the kidney immunopathology and may serve as biomarkers to identify patients at risk for developing LN and progressing to ESRD. PMID:27102764

  9. Herpes Zoster Infections in SLE in a University Hospital in Saudi Arabia: Risk Factors and Outcomes.

    PubMed

    Sayeeda, Afsar; Al Arfaj, Hussain; Khalil, Najma; Al Arfaj, A S

    2011-01-01

    Patients with SLE carry an increased risk of infection that account for 11-23% of all hospitalized patients and 50% of all SLE patients develop major infections during the course of their disease. Globally Herpes Zoster has been reported as the most frequent viral infection in SLE patients. We determined the clinical spectrum, disease sequelae and the risk factors associated with the development of Herpes Zoster in patients with SLE and their outcomes. Retrospective case control study of Herpes Zoster infections was done in SLE patients between 1982 and 2006. Cases were matched 1:2 to controls for age, race, sex and duration of follow up. Clinical features of the cases from the time of lupus diagnosis to the time of Zoster were compared to their respective controls over similar time periods. Thirty two SLE cases were compared to sixty four controls. Cases were more likely to have received cyclophosphamide (P = .0223) and intravenous methylprednisolone pulse therapy (P = .0026), MMF (P < .02), had leucopenia (P = .0407) and hemolytic anemia (P = .0344). More cases than controls had lupus nephritis, cerebritis, thrombocytopenia but the differences did not reach statistical significance. The mean oral prednisolone dose and proportion of patients receiving immunosuppressives including pulse methylprednisolone therapy, IV Cyclophosphamide and mycophenolate was significantly higher in patients with active SLE compared to patients with SLE in remission at the time of Herpes Zoster (P < .05). Disseminated Zoster developed in patients with active SLE (7/9) compared to patients with SLE in remission (0/23). None of the patients had postherpetic neuralgia or bacterial super infection. Immunosuppressive medications were discontinued at the time of diagnosis of Zoster in 19 of 32 patients and all patients received antiviral medications.There were no permanent neurologic deficits or deaths. We conclude that Herpes Zoster infections occur at increased frequency among patients

  10. Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care

    PubMed Central

    Urowitz, M; van Vollenhoven, R; Aranow, C; Fettiplace, J; Oldham, M; Wilson, B; Molta, C; Roth, D; Gordon, D

    2016-01-01

    Objective To examine long-term organ damage and safety following treatment with belimumab plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). Methods Pooled data were examined from two ongoing open-label studies that enrolled patients who completed BLISS-52 or BLISS-76. Patients received belimumab every four weeks plus SoC. SLICC Damage Index (SDI) values were assessed every 48 weeks (study years) following belimumab initiation (baseline). The primary endpoint was change in SDI from baseline at study years 5–6. Incidences of adverse events (AEs) were reported for the entire study period. Results The modified intent-to-treat (MITT) population comprised 998 patients. At baseline, 940 (94.2%) were female, mean (SD) age was 38.7 (11.49) years, and disease duration was 6.7 (6.24) years. The mean (SD) SELENA-SLEDAI and SDI scores were 8.2 (4.18) and 0.7 (1.19), respectively; 411 (41.2%) patients had organ damage (SDI = 1: 235 (23.5%); SDI ≥ 2: 176 (17.6%)) prior to belimumab. A total of 427 (42.8%) patients withdrew overall; the most common reasons were patient request (16.8%) and AEs (8.5%). The mean (SD) change in SDI was +0.2 (0.48) at study years 5–6 (n = 403); 343 (85.1%) patients had no change from baseline in SDI score (SDI +1: 46 (11.4%), SDI +2: 13 (3.2%), SDI +3: 1 (0.2%)). Of patients without organ damage at baseline, 211/241 (87.6%) had no change in SDI and the mean change (SD) in SDI was +0.2 (0.44). Of patients with organ damage at baseline, 132/162 (81.5%) had no change in SDI and the mean (SD) change in SDI was +0.2 (0.53). The probability of not having a worsening in SDI score was 0.88 (95% CI: 0.85, 0.91) and 0.75 (0.67, 0.81) in those without and with baseline damage, respectively (post hoc analysis). Drug-related AEs were reported for 433 (43.4%) patients; infections/infestations (282, 28.3%) and gastrointestinal disorders (139, 13.9%) were the most common. Conclusion Patients with SLE treated with long

  11. A Longitudinal Study of the Impact of Incident Organ Manifestations and Increased Disease Activity on Work Loss among Persons with SLE

    PubMed Central

    Yelin, Edward; Tonner, Chris; Trupin, Laura; Gansky, Stuart A.; Julian, Laura; Katz, Patricia; Yazdany, Jinoos; Kaiser, Rachel; Criswell, Lindsey A.

    2011-01-01

    Objective There is increasing evidence of the impact of SLE on employment, but few studies have had sufficient sample size and longitudinal follow-up to estimate the impact of specific manifestations or of increasing disease activity on employment. Methods Data derive from the UCSF Lupus Outcomes Study, a longitudinal cohort of 1204 persons with SLE sampled between 2002 and 2009. Of the 1204, 484 were working at baseline and had at least one follow-up interview. We used the Kaplan-Meier method to estimate the time between onset of thrombotic, neuropsychiatric, or musculoskeletal manifestations or of increased disease activity and work loss, and Cox proportional hazards regression to estimate the risk of work loss associated with the onset of specific manifestations, the number of manifestations, and increased activity, with and without adjustment for sociodemographic, employment, and SLE duration. Results By four years of follow-up, 57%, 34%, and 38% of those with thrombotic, musculoskeletal, and neuropsychiatric manifestations, respectively, had stopped working as had 42% of those with increased disease activity. On a bivariable basis, the risk of work loss was significantly higher among persons 55–64, and those with increased disease activity and each kind of manifestation. In multivariable analysis, older age, shorter job tenure, thrombotic and musculoskeletal manifestations, greater number of manifestations, and high levels of activity increased the risk of work loss. Conclusions Incident thrombosis and musculoskeletal manifestations, multiple manifestations, and increased disease activity are associated with the risk of work loss in SLE. PMID:22006458

  12. The effect of La(SSB) on PWM-induced immunoglobulin synthesis by anti-La(SSB) positive SLE patients and healthy controls.

    PubMed Central

    Smith, G; Morrison, C A; Maddison, P J

    1987-01-01

    The effect of affinity purified La(SSB) on immunoglobulin synthesis in vitro by mononuclear cells (MNC) from anti-La(SSB)-positive systemic lupus erythematosus (SLE) patients and healthy controls was studied. La(SSB) was prepared from calf thymus extract and characterized by SDS-polyacrylamide gel electrophoresis and immunoblotting. Silver staining of gels reveals nine major bands at 68 kD, 43-48 kD and 30-33 kD, of which six were recognized on immunoblots by sera from anti-La(SSB) positive SLE patients. Studies in vitro showed that La(SSB) alone did not stimulate total IgG or IgM synthesis in controls or SLE patients. Low concentrations of La(SSB) (optimal dose less than 0.02 ng/ml) suppressed pokeweed mitogen (PWM)-driven IgG synthesis by controls but not by anti-La(SSB) positive SLE patients. IgM responses were unaffected. Anti-La(SSB) and anti-DNA were detected in PWM-stimulated cultures from both study groups. In the presence of La(SSB) IgM anti-La(SSB) synthesis was enhanced in anti-La(SSB)-positive patients in a dose-dependent manner. In contrast, La(SSB) inhibited anti-La(SSB) production by controls (maximal at 2 ng/ml). La(SSB) had no effect on anti-DNA production in either group. Pre-incubation of control or anti-La(SSB)-positive SLE MNC with La(SSB) before addition to autologous PWM-driven cultures did not induce suppressor cells, although pre-incubation with Concanavalin A (ConA) did. Thus we suggest that La(SSB)-induced suppression of IgG synthesis in PWM-driven control cultures may not be due to induction of regulator cells, possibly missing from SLE cultures, but perhaps is a direct effect on B cells. Images Fig. 1 PMID:2958189

  13. Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices.

    PubMed

    Hegazy, M; Darwish, H; Darweesh, H; El-Shehaby, A; Emad, Y

    2010-04-01

    The aim of the present study is to assess serum APRIL levels in SLE patients versus rheumatoid arthritis (RA) patients and normal control and to correlate serum APRIL levels in SLE patients with disease activity indices. Serum APRIL levels was measured in 40 SLE patients, 20 patients with RA and 20 healthy volunteers who served as control group. Disease activity in SLE patients was assessed by the British Isles Lupus Assessment Group (BILAG) index and SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Significantly higher serum APRIL levels was observed in SLE patients compared to RA patients and normal controls (p=0.003 and p < or = 0.001, respectively). Positive correlations were found between serum APRIL levels and total BILAG index (r=0.486 and p=0.001), BILAG musculoskeletal score (r=0.848 and p < or = 0.001) and BILAG cardiorespiratory score (r=0.326 and 0.04). Serum APRIL was higher in SLE patients compared to RA patients and normal control subjects and positively correlates with BILAG index and higher levels may be associated with musculoskeletal manifestations of the disease. APRIL antagonism could be a potential therapeutic target in SLE. PMID:20116334

  14. Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy.

    PubMed

    Levite, Mia

    2014-08-01

    pathological effects: they activate glutamate/AMPA receptors, kill neurons by 'Excitotoxicity', and/or by complement activation modulated by complement regulatory proteins, cause multiple brain damage, aggravate chemoconvulsant-induced seizures, and also induce behavioral/motor impairments. Some patients with 'Autoimmune Epilepsy' that have anti-AMPA-GluR3B antibodies respond well (although sometimes transiently) to immunotherapy, and thanks to that have reduced seizures and overall improved neurological functions. (2) Anti-NMDA-NR1 antibodies are present in patients with autoimmune 'Anti-NMDA-receptor Encephalitis'. In humans, in animal models and in vitro the anti-NMDA-NR1 antibodies can be very pathogenic since they can cause a pronounced decrease of surface NMDA receptors expressed in hippocampal neurons, and also decrease the cluster density and synaptic localization of the NMDA receptors. The anti-NMDA-NR1 antibodies induce these effects by crosslinking and internalization of the NMDA receptors. Such changes can impair glutamate signaling via the NMDA receptors and lead to various neuronal/behavior/cognitive/psychiatric abnormalities. Anti-NMDA-NR1 antibodies are frequently present in high levels in the CSF of the patients with 'Anti-NMDA-receptor encephalitis' due to their intrathecal production. Many patients with 'Anti-NMDA receptor Encephalitis' respond well to several modes of immunotherapy. (3) Anti-NMDA-NR2A/B antibodies are present in a substantial number of patients with Systemic Lupus Erythematosus (SLE) with or without neuropsychiatric problems. The exact percentage of SLE patients having anti-NMDA-NR2A/B antibodies varies in different studies from 14 to 35%, and in one study such antibodies were found in 81% of patients with diffuse 'Neuropshychiatric SLE', and in 44% of patients with focal 'Neuropshychiatric SLE'. Anti-NMDA-NR2A/B antibodies are also present in subpopulations of patients with Epilepsy of several types, Encephalitis of several types (e

  15. Early cerebral volume reductions and their associations with reduced lupus disease activity in patients with newly-diagnosed systemic lupus erythematosus

    PubMed Central

    Mak, Anselm; Ho, Roger Chun-Man; Tng, Han-Ying; Koh, Hui Li; Chong, Joanna Su Xian; Zhou, Juan

    2016-01-01

    We examined if cerebral volume reduction occurs very early during the course of systemic lupus erythematosus (SLE), and observed prospectively whether gray (GMV) and white matter volumes (WMV) of the brain would improve with lowered SLE disease activity. T1-weighted MRI brain images were obtained from 14 healthy controls (HC) and 14 newly-diagnosed SLE patients within 5 months of diagnosis (S1) and after achieving low disease activity (S2). Whole brain voxel-based morphometry was used to detect differences in the GMV and WMV between SLE patients and HC and those between SLE patients at S1 and S2. SLE patients were found to have lower GMV than HC in the middle cingulate cortex, middle frontal gyrus and right supplementary motor area, and lower WMV in the superior longitudinal fasciculus, cingulum cingulate gyrus and inferior fronto-occipital fasciculus at both S1 and S2. Whole-brain voxel-wise analysis revealed increased GMV chiefly in the prefrontal regions at S2 compared to S1 in SLE patients. The GMV increase in the left superior frontal gyrus was significantly associated with lowered SLE disease activity. In conclusion, GMV and WMV reduced very early in SLE patients. Reduction of SLE disease activity was accompanied by region-specific GMV improvement in the prefrontal regions. PMID:26928214

  16. T cells as a therapeutic target in SLE

    PubMed Central

    Comte, Denis; Karampetsou, Maria P.; Tsokos, George C.

    2014-01-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by a loss of tolerance to multiple endogenous antigens. SLE etiology remains largely unknown, despite recent insight into the immunopathogenesis of the disease. T cells are important in the development of the disease by amplifying the immune response and contributing to organ damage. Aberrant signaling, cytokine secretion and tissue homing displayed by SLE T cells have been extensively studied and the underlying pathogenic molecular mechanisms are starting to be elucidated. T-cell targeted treatments are being explored in SLE patients. This review is an update on the T-cell abnormalities and related therapeutic options in SLE. PMID:25801878

  17. T lymphocyte expression of complement receptor 2 (CR2/CD21): a role in adhesive cell-cell interactions and dysregulation in a patient with systemic lupus erythematosus (SLE).

    PubMed

    Levy, E; Ambrus, J; Kahl, L; Molina, H; Tung, K; Holers, V M

    1992-11-01

    Complement receptor 2 (CR2, CD21), the receptor for both the C3d,g portion of human complement component C3 and the Epstein-Barr virus, has been recently described on peripheral T cells. By using dual stain flow cytometric analysis, we have also observed that a peripheral T lymphocyte subpopulation of normal healthy donors bears CR2 in a range varying from 1.1 to 23.2% (mean 12.6%) of total CD3+ cells. T lymphocytes from nine patients with inactive SLE expressed CR2 in a similar range. Three patients with active SLE were also studied. One of them, having neuropathy and glomerulonephritis, displayed an expansion of the CR2 T cell subpopulation which reached as much as 89% of total CD3+ cells. To examine potential functional roles of T cell CR2, cells from a Jurkat-derived CR2 expressing T cell line were found to bind in vitro to human CR2-, complement-coated K562 cell targets in a CR2- and complement-dependent fashion. Based on these studies, we hypothesize that CR2 might act to increase adherence of T cells to nucleated target cells bearing C3d,g, a function which may be relevant to cytotoxicity or other T cell activities requiring cell-cell interaction. PMID:1424280

  18. Preferential Binding to Elk-1 by SLE-Associated IL10 Risk Allele Upregulates IL10 Expression

    PubMed Central

    Kelly, Jennifer A.; Brown, Elizabeth E.; Harley, John B.; Bae, Sang-Cheol; Alarcόn-Riquelme, Marta E.; Edberg, Jeffrey C.; Kimberly, Robert P.; Ramsey-Goldman, Rosalind; Petri, Michelle A.; Reveille, John D.; Vilá, Luis M.; Alarcón, Graciela S.; Kaufman, Kenneth M.; Vyse, Timothy J.; Jacob, Chaim O.; Gaffney, Patrick M.; Sivils, Kathy Moser; James, Judith A.; Kamen, Diane L.; Gilkeson, Gary S.; Niewold, Timothy B.; Merrill, Joan T.; Scofield, R. Hal; Criswell, Lindsey A.; Stevens, Anne M.; Boackle, Susan A.; Kim, Jae-Hoon; Choi, Jiyoung; Pons-Estel, Bernardo A.; Freedman, Barry I.; Anaya, Juan-Manuel; Martin, Javier; Yu, C. Yung; Chang, Deh-Ming; Song, Yeong Wook; Langefeld, Carl D.; Chen, Weiling; Grossman, Jennifer M.; Cantor, Rita M.; Hahn, Bevra H.; Tsao, Betty P.

    2013-01-01

    Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL

  19. Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations

    PubMed Central

    Wang, Chuan; Ahlford, Annika; Järvinen, Tiina M; Nordmark, Gunnel; Eloranta, Maija-Leena; Gunnarsson, Iva; Svenungsson, Elisabet; Padyukov, Leonid; Sturfelt, Gunnar; Jönsen, Andreas; Bengtsson, Anders A; Truedsson, Lennart; Eriksson, Catharina; Rantapää-Dahlqvist, Solbritt; Sjöwall, Christopher; Julkunen, Heikki; Criswell, Lindsey A; Graham, Robert R; Behrens, Timothy W; Kere, Juha; Rönnblom, Lars; Syvänen, Ann-Christine; Sandling, Johanna K

    2013-01-01

    Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case–control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities. PMID:23249952

  20. Posterior reversible encephalopathy syndrome: another manifestation of CNS SLE?

    PubMed

    Ishimori, M L; Pressman, B D; Wallace, D J; Weisman, M H

    2007-01-01

    A variety of neuropsychiatric findings may complicate systemic lupus erythematosus (SLE) and pose diagnostic and therapeutic dilemmas. We describe the clinical and radiographic features of posterior reversible encephalopathy syndrome (PRES) and distinguish PRES from other conditions seen in SLE. Patient charts and magnetic resonance imaging (MRI) findings of four patients with SLE on immunosuppressive therapy with acute or subacute neurologic changes initially suggesting cerebritis or stroke were reviewed. The English language literature was reviewed using the Medline databases from 1996-2006 for other reports of PRES with SLE. Literature review yielded 26 other SLE cases reported with PRES. SLE patients with PRES were more commonly on immunosuppressive drugs, had episodes of relative hypertension, and had renal involvement. Characteristic findings are seen on MRI, which differentiate PRES from other CNS complications of SLE. Clinical and radiographic resolution of abnormalities within 1-4 weeks is typically seen. PRES has been increasingly recognized. Reversible changes are found on brain MRI accompanied by sometimes dramatic signs and symptoms. The therapeutic implications for separating PRES from stroke or cerebritis are important. We propose that PRES should be considered in the differential diagnosis in SLE patients with new-onset neurologic signs and symptoms. PMID:17664235

  1. Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus.

    PubMed

    Chu, Man; Wong, Chun Kwok; Cai, Zhe; Dong, Jie; Jiao, Delong; Kam, Ngar Woon; Lam, Christopher Wai Kei; Tam, Lai Shan

    2015-01-01

    We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19⁺CD24(high)CD27⁺ regulatory B (Breg) lymphocytes of peripheral blood from 43 SLE patients and 16 normal control (NC) subjects were studied using ELISA and flow cytometry. Plasma cytokines/chemokines and ex vivo productions of cytokine/chemokine from peripheral blood mononuclear cells (PBMC) stimulated with recombinant IL-36 were determined by Luminex multiplex assay. Plasma concentrations of IL-36α, IL-36γ and the proportions of circulating IL-36R-positive CD19⁺ B lymphocytes in total B lymphocytes and PBMC were significantly increased in active SLE patients compared with NC (all p < 0.05). Plasma IL-36α and IL-36γ correlated positively with SLE disease activity and elevated plasma IL-10 concentration (all p < 0.05). The frequencies of circulating Breg lymphocytes in total B lymphocytes and PBMC were significantly decreased in both inactive and active SLE patients compared with NC (all p < 0.01). The frequency of Breg lymphocytes in total B lymphocytes correlated negatively with the proportion of IL-36R-positive B lymphocytes (p < 0.05). IL-36α exerted substantial proinflammatory effect in PBMC from SLE patients by inducing the production of IL-6 and CXCL8. Upon stimulation with IL-36α and IL-36γ, ex vivo productions of IL-6 and CXCL8 were significantly increased in SLE patients compared with NC (all p < 0.05). This cross-sectional study demonstrated that over expression of circulating IL-36α may exert a proinflammatory effect as observed in human SLE. PMID:26516833

  2. Deranged bioenergetics and defective redox capacity in T lymphocytes and neutrophils are related to cellular dysfunction and increased oxidative stress in patients with active systemic lupus erythematosus.

    PubMed

    Li, Ko-Jen; Wu, Cheng-Han; Hsieh, Song-Chou; Lu, Ming-Chi; Tsai, Chang-Youh; Yu, Chia-Li

    2012-01-01

    Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyl)lysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE) than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox) capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T) and polymorphonuclear neutrophils (PMN) of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px) and γ-glutamyl-transpeptidase (GGT), was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients. PMID:22007252

  3. Increased photosensitivity to near-ultraviolet light in murine SLE

    SciTech Connect

    Golan, D.T.; Borel, Y.

    1984-02-01

    The authors investigated whether there is increased susceptibility to near-UVL in murine SLE. Cultured spleen cells from either strain of mice with lupus disease or conventional strains of mice were exposed to different UVL fractions in vitro. The effect of DNA synthesis, release, and repair was examined. DNA synthesis and release was measured as percent of (/sup 3/H)thymidine (dT) uptake into either total acid-precipitable radioactive material of cell sediment plus supernatant, or that of the medium alone, whereas hydroxyurea-resistant dT incorporation represented DNA repair. The data indicate that all SLE strains, in contrast to all non-SLE strains, show increased DNA synthesis and release after UV-A exposure. In addition, all murine SLE strains demonstrate increased susceptibility to induction of DNA damage by UV-A. The significance of these observations in relation to the clinical activity of SLE after sunlight exposure is discussed.

  4. Dietary extra virgin olive oil attenuates kidney injury in pristane-induced SLE model via activation of HO-1/Nrf-2 antioxidant pathway and suppression of JAK/STAT, NF-κB and MAPK activation.

    PubMed

    Aparicio-Soto, Marina; Sánchez-Hidalgo, Marina; Cárdeno, Ana; Rosillo, María Ángeles; Sánchez-Fidalgo, Susana; Utrilla, Jose; Martín-Lacave, Inés; Alarcón-de-la-Lastra, Catalina

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a widespread organ involvement. Recent studies have suggested that extra virgin olive oil (EVOO) might possess preventive effects on this immunoinflammation-related disease. However, its role in SLE remained unknown. In this work, we evaluated the effects of EVOO diet in a pristane-induced SLE model in mice. Three-month-old mice received an injection of pristane or saline solution and were fed with different experimental diets: sunflower oil diet or EVOO diet. After 24weeks, mice were sacrificed, spleens were collected and kidneys were removed for immunoinflammatory detections. The kidney expression of microsomal prostaglandin E synthase 1, heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf-2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear transcription factor-kappa B (NF-κB) pathways were studied by western blotting. In addition to macroscopic and histological analyses, serum matrix metalloproteinase 3 (MMP-3) levels and proinflammatory cytokines production in splenocytes were evaluated by enzyme-linked immunoassay. We have demonstrated that EVOO diet significantly reduced renal damage and decreased MMP-3 serum and PGE2 kidney levels as well as the proinflammatory cytokines production in splenocytes. Our data indicate that Nrf-2 and HO-1 protein expressions were up-regulated in those mice fed with EVOO and the activation of JAK/STAT, MAPK and NF-κB pathways were drastically ameliorated. These results support the interest of EVOO as a beneficial functional food exerting a preventive/palliative role in the management of SLE. PMID:26525667

  5. Histiocytic necrotizing lymphadenitis in the context of systemic lupus erythematosus (SLE): Is histiocytic necrotizing lymphadenitis in SLE associated with skin lesions?

    PubMed

    Kim, S K; Kang, M S; Yoon, B Y; Kim, D Y; Cho, S K; Bae, S C; Her, M Y

    2011-07-01

    Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi's disease, is a benign and self-limiting lymphadenopathy that typically affects young Asian females. It presents with lymphadenopathy, usually cervical, accompanied by fever, chills and leukopenia. Although the association between systemic lupus erythematosus (SLE) and HNL is rare, the number of reports of HNL in SLE patients is increasing. We present nine cases of HNL in patients with SLE. Among the seven patients with diverse skin manifestations, three had skin manifestations that were histologically compatible with SLE. A review of previous reports in the literature showed that cutaneous involvement was commonly found in HNL in association with SLE. In the patients who had simultaneous onset of both diseases, lupus flare-ups were commonly observed. We suggest that HNL in SLE patients is associated with cutaneous manifestations. This report contributes to our understanding of the relationship between these diseases. PMID:21562017

  6. Epratuzumab for patients with moderate to severe flaring SLE: health-related quality of life outcomes and corticosteroid use in the randomized controlled ALLEVIATE trials and extension study SL0006

    PubMed Central

    Petri, Michelle; Kalunian, Kenneth; Gordon, Caroline; Wallace, Daniel J.; Hobbs, Kathryn; Kelley, Lexy; Kilgallen, Brian; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    Objective. To evaluate health-related quality of life (HRQOL) and corticosteroid use in patients with moderate to severely active SLE enrolled in two international, multicentre, randomized controlled trials of epratuzumab (ALLEVIATE-1 and -2) and a long-term extension study (SL0006). Methods. Ninety ALLEVIATE patients (43% BILAG A, mean BILAG score 13.2) were randomized to receive 360 mg/m2 (n = 42) or 720 mg/m2 (n = 11) epratuzumab or placebo (n = 37), plus standard of care, in 12-week cycles. Corticosteroid use, patient and physician global assessments of disease activity (PtGA and PGA) and 36-item Medical Outcomes Survey Short Form (SF-36) results were recorded at baseline and every 4 weeks. Both trials were prematurely discontinued due to a drug supply interruption; patients followed for ≥6 months were analysed. Twenty-nine patients continued in SL0006, with interim analysis at a median exposure of 120 (range 13–184) weeks. Results. At week 12, proportions of patients with a PGA ≥20% above baseline or with a PtGA improvement greater than or equal to the minimum clinically important difference were higher in the epratuzumab arms than the placebo arm. PGA and PtGA improvements were sustained but did not reach statistical significance. At week 24, mean cumulative corticosteroid doses with epratuzumab 360 and 720 mg/m2 were 1051 and 1973 mg less than placebo (P = 0.034 and 0.081, respectively). At week 48, SF-36 scores approached or exceeded US age- and gender-matched norms in five domains with the 360 mg/m2 treatment. Improvements were maintained in SL0006 over ∼2 years. Conclusion. Epratuzumab treatment produced clinically meaningful and sustained improvements in PGA, PtGA and HRQOL and reductions in corticosteroid doses. PMID:24273022

  7. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system.

    PubMed

    Alexander, Tobias; Thiel, Andreas; Rosen, Oliver; Massenkeil, Gero; Sattler, Arne; Kohler, Siegfried; Mei, Henrik; Radtke, Hartmut; Gromnica-Ihle, Erika; Burmester, Gerd-Rüdiger; Arnold, Renate; Radbruch, Andreas; Hiepe, Falk

    2009-01-01

    Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE. PMID:18824594

  8. Post-steroid neuropsychiatric manifestations are significantly more frequent in SLE compared with other systemic autoimmune diseases and predict better prognosis compared with de novo neuropsychiatric SLE.

    PubMed

    Shimizu, Yuka; Yasuda, Shinsuke; Kako, Yuki; Nakagawa, Shin; Kanda, Masatoshi; Hisada, Ryo; Ohmura, Kazumasa; Shimamura, Sanae; Shida, Haruki; Fujieda, Yuichiro; Kato, Masaru; Oku, Kenji; Bohgaki, Toshiyuki; Horita, Tetsuya; Kusumi, Ichiro; Atsumi, Tatsuya

    2016-08-01

    In patients with systemic lupus erythematosus (SLE), neuropsychiatric (NP) symptoms sometimes occur after administration of corticosteroids, making differential diagnosis between NPSLE and steroid-induced psychosis challenging for clinicians. The aim of this study was to clarify the characteristics of post-steroid NP disease (PSNP) in patients with SLE. Clinical courses of 146 patients with SLE and 162 with other systemic autoimmune diseases, all in the absence of NP manifestations on admission, were retrospectively analyzed. Forty-three NPSLE patients on admission (de novo NPSLE) were also investigated. All patients were consecutively recruited and treated with 40mg/day or more of prednisolone in Hokkaido University Hospital between April 2002 and March 2015. The prevalence of PSNP was strikingly higher in SLE patients than other systemic autoimmune diseases (24.7% vs. 7.4%, OR 4.09, 95% CI 2.04-8.22). As independent risk factors to develop PSNP in SLE patients, past history of mental disorder and the presence of antiphospholipid syndrome were identified using multiple logistic regression analysis. In patients with PSNP-SLE, mood disorder was significantly more frequent than in de novo NPSLE (47.2% vs. 20.9%, OR 3.38, 95% CI 1.26-9.04). Of PSNP-SLE patients, two-thirds were with one or more abnormal findings in cerebrospinal fluid, electroencephalogram, MRI or SPECT. Majority of our PSNP-SLE patients received intensified immunosuppressive treatments and experienced improvement in most cases. PSNP-SLE had better relapse-free survival than de novo NPSLE (p<0.05, log rank test). In conclusion, PSNP frequently occurred in patients with SLE and treated successfully with immunosuppressive therapy, indicating that NPSLE is likely to harbor patients with PSNP-SLE. PMID:27016478

  9. Optimizing outcome in SLE: treating-to-target and definition of treatment goals.

    PubMed

    Doria, Andrea; Gatto, Mariele; Zen, Margherita; Iaccarino, Luca; Punzi, Leonardo

    2014-07-01

    Patients affected with systemic lupus erythematosus (SLE) display poor-long term prognosis and increased mortality in respect of general population. This may be due to continuous organ damage accrual which is fostered both by persistent disease activity (mainly in the short term) and prolonged corticosteroid exposure (mainly in the long term). The effort of defining novel therapeutic goals to which patients should be treated in order to have their prognosis improved is named treat-to-target. Remission in SLE was shown to be associated with better outcome and prolonged survival; in clinical practice, patients may experience either complete or clinical remission, which are defined as complete clinical/serological healing or no clinical signs of lupus with active serology, respectively. The main treat-to-target in SLE is complete remission, however since longitudinal observations suggest that clinical remission or low disease activity even with minimal corticosteroid intake do improve patients prognosis and survival as well, they may be assumed as acceptable alternative targets. Suitable therapeutic strategies have to be defined in order for these goals to be achieved including early diagnosis, effective treatment and proper corticosteroid tapering which in turn require development of more reliable serum biomarkers for early disease detection and less toxic targeted therapies with a steroid-sparing potential. PMID:24480071

  10. Association of LY9 in UK and Canadian SLE families.

    PubMed

    Cunninghame Graham, D S; Vyse, T J; Fortin, P R; Montpetit, A; Cai, Y-c; Lim, S; McKenzie, T; Farwell, L; Rhodes, B; Chad, L; Hudson, T J; Sharpe, A; Terhorst, C; Greenwood, C M T; Wither, J; Rioux, J D

    2008-03-01

    Systemic lupus erythematosus (SLE) is a complex disease trait of unknown aetiology. Genome-wide linkage studies in human SLE identified several linkage regions, including one at 1q23, which contains multiple susceptibility genes, including the members of the signalling lymphocyte activation molecule (SLAM) locus. In mice there is a syntenic linkage region, Sle1. The SLAM genes are functionally related cell-surface receptors, which regulate signal transduction of cells in the immune system. Family-based association study in UK and Canadian SLE families identified variants in the promoter and coding region of SLAMF7 and LY9 contributing to SLE disease susceptibility. The strongest association was from rs509749, in exon 8 of LY9 (P=0.00209). rs509749 encodes a Val/Met nonsynonymous change in amino acid 602 in the cytoplasmic domain of LY9. In the parents and affected individuals from the Canadian SLE families, the risk allele of rs509049 skews the T-cell population by increasing the number of CD8+ memory T cells, while decreasing the proportion of CD4+ naïve T cells and activated T cells. Since rs509749 lies within the consensus binding site for SAP/SH2D1a, which influences downstream signalling events from LY9, the mechanism for increased CD8+ memory T cells may include differential binding SAP/SH2D1a to the cytoplasmic domain of LY9. PMID:18216865

  11. Prevalence of metabolic syndrome in a cohort of systemic lupus erythematosus patients from Northeastern Brazil: association with disease activity, nephritis, smoking, and age.

    PubMed

    Medeiros, Marta Maria das Chagas; Xavier de Oliveira, Ídila Mont'Alverne; Ribeiro, Ádilla Thaysa Mendes

    2016-01-01

    Systemic lupus erythematosus (SLE), an autoimmune inflammatory disease, is associated with an increased prevalence of accelerated atherosclerosis and cardiovascular events. Metabolic syndrome (MetS) is a set of cardiovascular risk factors in SLE patients, which may lead to a proinflammatory condition and increased morbidity and mortality. The objective of this study was to evaluate the prevalence of MetS in a cohort of SLE patients versus healthy controls, and to analyze the association of clinical and demographic factors. SLE patients (n = 146) treated at a Northeast Brazilian university hospital were evaluated with regard to demographic, clinical, laboratory, and anthropometric parameters and compared to controls (n = 101). MetS was diagnosed according to the definition of 2005 NCEP/ATP III. The average age of SLE patients was 41.7 ± 12.5 years, and 91.8 % were female. MetS was significantly more prevalent in SLE patients (45.2 %) than in controls (32.7 %; p = 0.04). The MetS components such as hypertension, diabetes, and hypertriglyceridemia were significantly more prevalent in SLE. In the univariate analysis, MetS in SLE patients was associated with age, disease duration, Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index, smoking, menopause, nephritis, cyclophosphamide use, prednisone dose, and chloroquine use, which appeared to have a protective effect. In the logistic regression analysis, age, disease activity, nephritis, and smoking were statistically significant. The prevalence of MetS observed in our cohort of SLE patients from Northeastern Brazil is higher than controls. MetS components should be routinely investigated to minimize the occurrence of MetS and associated cardiovascular morbidity and mortality. PMID:26149124

  12. Pregnancy in women with systemic lupus erythematosus (SLE).

    PubMed

    Moroni, Gabriella; Ponticelli, Claudio

    2016-07-01

    For many years pregnancy has been contraindicated in patients with SLE, particularly when kidney involvement was present. Today, pregnancy is no longer considered impossible in women with lupus. Yet, lupus pregnancies are still considered high-risk. The prognosis has considerably improved for pregnant women but the fetal risk, although progressively reduced, is still higher in pregnancies of patients with SLE than in pregnancies of healthy women. Miscarriage, premature delivery, and preeclampsia, as well as heart problems in the baby are the major complications that can occur. In this paper we will review the outcome of pregnant women with SLE, the influence of lupus on fetal outcome, the effects of pregnancy on lupus, and the management of pregnant lupus patients based on our personal experience and the revision of the most recent and significant papers on the subject. PMID:27142327

  13. Herpes Zoster as the Presenting Manifestation of Systemic Lupus Erythematosus (SLE): A Rare Case Report

    PubMed Central

    Qureshi, Arshna

    2016-01-01

    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and is usually diagnosed with the SLICC criteria. Here we report a case of SLE presenting as Herpes Zoster (HZ). She had presented with painful vesicular eruptions from 8th thoracic nerve to 10th thoracic nerve segments and oliguria. There were no clinical manifestations suggestive of SLE. However, on further workup, haematological and immunologic laboratory profiles were suggestive of SLE. A diagnosis of lupus nephropathy was confirmed by renal biopsy and final diagnosis of SLE as the underlying systemic illness associated with HZ was established. We report this case because this patient had none of the manifestations of SLE, as a result of which this would have been an incomplete diagnosis. PMID:27134921

  14. Correlations between IL-2 enhancing activity and clinical parameters in patients with rheumatoid arthritis and systemic lupus erythematosus.

    PubMed

    Tomura, K; Kang, H; Mitamura, K; Takei, M; Yamagami, K; Karasaki, M; Nishinarita, S; Hayama, T; Sawada, S; Horie, T

    1991-04-01

    In a previous paper (Tomura, K. et al. Tohoku J. Exp. Med., 1989, 159, 171-183), we discovered IL-2 enhancing factor(s) designated B cell derived-growth enhancing factor-2 (BGEF-2), which enhanced IL-2 dependent cell proliferation, and reported that BGEF-2 was produced by B cells of the patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) only when they were in the active stage of the disease. In this paper, we studied relationship between each IL-2 enhancing activity from B cell supernatant of the patients with these diseases and clinical parameters. IL-2 enhancing activities did not correlate with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but correlated with plasma concentrations of gamma-globulin from the patients with RA and SLE in the active stages. IL-2 enhancing activities correlated with hypocomplementemia and leukocytopenia in the patients with SLE, and also correlated with RAHA titer in the patients with RA. Moreover, on several patients with RA or SLE in the active stages, diminution of IL-2 enhancing activity was found when they were in the remission stage after treatments. These findings suggested that IL-2 enhancing activity (i.e., BGEF-2 activity) correlated with activity of these diseases and supported the hypothesis that BGEF-2 played an important role in the polyclonal B cell activation and autoantibody production in patients with these diseases. PMID:1715616

  15. SLE and Virasoro Representations: Fusion

    NASA Astrophysics Data System (ADS)

    Dubédat, Julien

    2015-06-01

    We continue the study of null-vector equations in relation with partition functions of (systems of) Schramm-Loewner Evolutions (SLEs) by considering the question of fusion. Starting from n commuting SLEs seeded at distinct points, the partition function satisfies n null-vector equations (at level 2). We show how to obtain higher level null-vector equations by coalescing the seeds one by one. As an example, we extend Schramm's formula (for the position of a marked bulk point relatively to a chordal SLE trace) to an arbitrary number of SLE strands. The argument combines input from representation theory—the study of Verma modules for the Virasoro algebra—with regularity estimates, themselves based on hypoellipticity and stochastic flow arguments.

  16. Spore germination mediated by Bacillus megaterium QM B1551 SleL and YpeB.

    PubMed

    Ūstok, Fatma Işik; Packman, Len C; Lowe, Christopher R; Christie, Graham

    2014-03-01

    Previous work demonstrated that Bacillus megaterium QM B1551 spores that are null for the sleB and cwlJ genes, which encode cortex-lytic enzymes (CLEs), either of which is required for efficient cortex hydrolysis in Bacillus spores, could germinate efficiently when complemented with a plasmid-borne copy of ypeB plus the nonlytic portion of sleB encoding the N-terminal domain of SleB (sleB(N)). The current study demonstrates that the defective germination phenotype of B. megaterium sleB cwlJ spores can partially be restored when they are complemented with plasmid-borne ypeB alone. However, efficient germination in this genetic background requires the presence of sleL, which in this species was suggested previously to encode a nonlytic epimerase. Recombinant B. megaterium SleL showed little, or no, activity against purified spore sacculi, cortical fragments, or decoated spore substrates. However, analysis of muropeptides generated by the combined activities of recombinant SleB and SleL against spore sacculi revealed that B. megaterium SleL is actually an N-acetylglucosaminidase, albeit with apparent reduced activity compared to that of the homologous Bacillus cereus protein. Additionally, decoated spores were induced to release a significant proportion of dipicolinic acid (DPA) from the spore core when incubated with recombinant SleL plus YpeB, although optimal DPA release required the presence of endogenous CLEs. The physiological basis that underpins this newly identified dependency between SleL and YpeB is not clear, since pulldown assays indicated that the proteins do not interact physically in vitro. PMID:24375103

  17. Spore Germination Mediated by Bacillus megaterium QM B1551 SleL and YpeB

    PubMed Central

    Üstok, Fatma Işık; Packman, Len C.; Lowe, Christopher R.

    2014-01-01

    Previous work demonstrated that Bacillus megaterium QM B1551 spores that are null for the sleB and cwlJ genes, which encode cortex-lytic enzymes (CLEs), either of which is required for efficient cortex hydrolysis in Bacillus spores, could germinate efficiently when complemented with a plasmid-borne copy of ypeB plus the nonlytic portion of sleB encoding the N-terminal domain of SleB (sleBN). The current study demonstrates that the defective germination phenotype of B. megaterium sleB cwlJ spores can partially be restored when they are complemented with plasmid-borne ypeB alone. However, efficient germination in this genetic background requires the presence of sleL, which in this species was suggested previously to encode a nonlytic epimerase. Recombinant B. megaterium SleL showed little, or no, activity against purified spore sacculi, cortical fragments, or decoated spore substrates. However, analysis of muropeptides generated by the combined activities of recombinant SleB and SleL against spore sacculi revealed that B. megaterium SleL is actually an N-acetylglucosaminidase, albeit with apparent reduced activity compared to that of the homologous Bacillus cereus protein. Additionally, decoated spores were induced to release a significant proportion of dipicolinic acid (DPA) from the spore core when incubated with recombinant SleL plus YpeB, although optimal DPA release required the presence of endogenous CLEs. The physiological basis that underpins this newly identified dependency between SleL and YpeB is not clear, since pulldown assays indicated that the proteins do not interact physically in vitro. PMID:24375103

  18. SLE or hypothyroidism: who can triumph in cardiac tamponade?

    PubMed

    Chaudhari, Sameer Sadashiv; Wankhedkar, Kashmira Pramod; Mushiyev, Savi

    2015-01-01

    A 36-year-old Hispanic woman with a history of systemic lupus erythaematosus (SLE) in remission presented with progressive dyspnoea, bilateral leg swelling and increasing fatigue with rapid weight gain over the past few months. Her physical examination showed mildly tender thyromegaly and pericardial rub. Investigations showed new onset marked hypothyroidism as well as an active lupus serology with echocardiogram confirming severe pericardial effusion and a tamponade phenomenon. Urgent pericardiocentesis relieved her acute symptoms, and prompt treatment with thyroxine replacement and immunosuppression for lupus disease was initiated. Pericardial fluid analysis remained negative for any malignancy and/or infection/s. The patient had a gradual and consistent improvement with this treatment. She was discharged and appeared to be clinically stable at subsequent follow-up visits. However, the case remained a diagnostic dilemma over whether the tamponade was being driven by hypothyroidism versus lupus, leaving us with an opportunity to explore further. PMID:25750217

  19. Standardised incidence ratios (SIRs) for cancer after renal transplant in systemic lupus erythematosus (SLE) and non-SLE recipients

    PubMed Central

    Ramsey-Goldman, Rosalind; Brar, Amarpali; Richardson, Carrie; Salifu, Moro O; Clarke, Ann; Bernatsky, Sasha; Stefanov, Dimitre G; Jindal, Rahul M

    2016-01-01

    Objective We investigated malignancy risk after renal transplantation in patients with and without systemic lupus erythematosus (SLE). Methods Using the United States Renal Data System from 2001 to 2009, 143 652 renal transplant recipients with and without SLE contributed 585 420 patient-years of follow-up to determine incident cancers using Medicare claims codes. We calculated standardised incidence ratios (SIRs) of cancer by group using age, sex, race/ethnicity-specific and calendar year-specific cancer rates compared with the US population. Results 10 160 cancers occurred at least 3 months after renal transplant. Overall cancer risk was increased in both SLE and non-SLE groups compared with the US general population, SIR 3.5 (95% CI 2.1 to 5.7) and SIR 3.7 (95% CI 2.4 to 5.7), respectively. Lip/oropharyngeal, Kaposi, neuroendocrine, thyroid, renal, cervical, lymphoma, liver, colorectal and breast cancers were increased in both groups, whereas only melanoma was increased in SLE and lung cancer was increased in non-SLE. In Cox regression analysis, SLE status (HR 1.1, 95% CI 0.9 to 1.3) was not associated with increased risk of developing cancer, adjusted for other independent risk factors for developing cancer in renal transplant recipients. We found that smoking (HR 2.2, 95% CI 1.2 to 4.0), cytomegalovirus positivity at time of transplant (HR 1.3, 95% CI 1.2 to 1.4), white race (HR 1.2, 95% CI 1.2 to 1.3) and older recipient age at time of transplantation (HR 1.0 95% CI 1.0 to 1.2) were associated with an increased risk for development of cancer, whereas shorter time on dialysis, Epstein-Barr virus or HIV were associated with a lower risk for development of cancer. Conclusions Cancer risk in renal transplant recipients appeared similar in SLE and non-SLE subjects, aside from melanoma. Renal transplant recipients may need targeted counselling regarding surveillance and modifiable risk factors. PMID:27335659

  20. Vitamin D Status in Patients with Systemic Lupus Erythematosus in Serbia: Correlation with Disease Activity and Clinical Manifestations

    PubMed Central

    Miskovic, Rada; Plavsic, Aleksandra; Raskovic, Sanvila; Jovicic, Zikica; Bolpacic, Jasna

    2015-01-01

    BACKGROUND: Numerous studies indicate potential role of vitamin D as an important factor in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). Patients with SLE are especially prone to the development of vitamin D deficiency due to the nature of their illness. AIM: The aims of our study were to determine the prevalence of vitamin D insufficiency and deficiency in patients with SLE in Serbia, to identify clinical variables associated with vitamin D status and to examine the impact of vitamin D status on disease activity and presence of specific lupus autoantibodies. MATERIAL AND METHODS: The study included 46 patients with SLE. Serum 25(OH)D concentration was measured by electrohemiluminiscent immunoassay. RESULTS: The mean serum concentration of 25(OH)D was 11.9 ± 7.3 ng/ml. The prevalence of insufficiency was 32.6%, while the prevalence of deficiency was 67.4%. There was no association between vitamin D status and photosensitivity, skin lesions, arthritis and lupus nephritis. Vitamin D status was not associated with the presence of specific autoantibodies. There was no correlation between disease activity assessed by SLEDAI scale with the concentration of 25(OH)D. Patients who used vitamin D supplements and calcium did not have a significantly higher concentration of 25(OH)D. CONCLUSION: In conclusion, vitamin D deficiency is common in patients with SLE.

  1. Smoking, disease activity, permanent damage and dsDNA autoantibody production in patients with systemic lupus erythematosus.

    PubMed

    Ekblom-Kullberg, Susanne; Kautiainen, Hannu; Alha, Pirkko; Leirisalo-Repo, Marjatta; Miettinen, Aaro; Julkunen, Heikki

    2014-03-01

    The aim was to study the association of smoking with the activity and severity of systemic lupus erythematosus (SLE) and the production of antibodies to dsDNA. The study included 223 SLE patients attending the outpatient clinics at Helsinki University Central Hospital. The history of smoking was obtained by personal interview, and clinical data related to SLE by interview, clinical examination and chart review. The activity of SLE was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score and permanent damage by the SLICC/ACR score. Antibodies to dsDNA were determined by three ELISA assays, by the indirect immunofluorescence technique using Crithidia luciliae cells as substrates and by the Farr assay. There were no significant differences in the SLEDAI scores between current smokers (73 patients), ex-smokers (59) and never-smokers (91), though current smokers tended to have lower disease activity. The SLICC/ACR scores between the groups were practically equal. Current smokers had significantly lower levels of antibodies to dsDNA than ex- and never-smokers (p = 0.025). Our study suggests that cigarette smoke may have immunosuppressive effect on autoantibody production in patients with SLE. Permanent damage was not found to be associated with smoking. PMID:24170320

  2. Circulating interferon-α2 levels are increased in the majority of patients with systemic lupus erythematosus and are associated with disease activity and multiple cytokine activation.

    PubMed

    Becker-Merok, A; Østli-Eilersten, G; Lester, S; Nossent, Jc

    2013-02-01

    Mutations in interferon (IFN) regulatory factor genes and the biological activity of type I IFN on expression of specific genes that are induced by IFN have been associated with various aspects of systemic lupus erythematosus (SLE). Circulating levels of IFN-α in SLE has not been extensively studied because of limited sensitivity of available ELISA assays. We performed a cross-sectional case-control study where circulating levels of IFN-α2 were measured by a highly sensitive, solution phase multiplex magnetized bead assay and investigated the relation of IFN-α2 with autoantibody profiles, clinical disease activity and levels of inflammatory cytokines in SLE patients (n = 87). Cytokine levels were determined on stored sera aliquots with cut-off levels determined by the geometric mean + 2SD in healthy controls (n = 27). IFN-α2 levels were increased in 64% of SLE patients, who displayed more renal disease and higher disease activity (p = 0.06) and had a significantly higher sum of activated cytokines (median 4.5, range 7) compared to patients with normal IFN-α2 (median one, range 3; p < 0.001). Solution phase micro-bead assay thus identified increased IFN-α2 levels in two-thirds of SLE patients with longstanding disease. The association with clinical disease and activation of multiple inflammatory cytokines supports a role for IFN-α2 in disease perpetuation in a large subset of SLE patients. PMID:23213068

  3. SLE-associated risk factors affect DC function

    PubMed Central

    Son, Myoungsun; Kim, Sun Jung; Diamond, Betty

    2016-01-01

    Numerous risk alleles for systemic lupus erythematosus (SLE) have now been identified. Analysis of the expression of genes with risk alleles in cells of hematopoietic origin demonstrates them to be most abundantly expressed in B cells and dendritic cells (DCs), suggesting that these cell types may be the drivers of the inflammatory changes seen in SLE. DCs are of particular interest as they act to connect the innate and the adaptive immune response. Thus, DCs can transform inflammation into autoimmunity, and autoantibodies are the hallmark of SLE. In this review, we focus on mechanisms of tolerance that maintain DCs in a non-activated, non-immunogenic state. We demonstrate, using examples from our own studies, how alterations in DC function stemming from either DC-intrinsic abnormalities or DC-extrinsic regulators of function can predispose to autoimmunity. PMID:26683148

  4. The efficacy of novel B cell biologics as the future of SLE treatment: a review.

    PubMed

    Kamal, Ameer; Khamashta, Munther

    2014-11-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with wide ranging multi-systemic effects. Current understanding centralises B cells in SLE pathogenesis with clinical features resulting from autoantibody formation, immune complex deposition, antigen presentation and cytokine activation. Existing standard of care therapies generates adverse side effects; secondary to corticosteroid use and untargeted immunosuppression. The inability to uphold remission and abolish the disease process, in addition to the increasing numbers of patients seen with refractory disease with these therapies, has provoked the development of novel B cell biologics targeting specific pathogenic pathways fundamental to the SLE disease process. Current evidence highlighting the efficacy of Rituximab, Ocrelizumab and Epratuzumab in inducing B cell depletion and achieving disease amelioration through specific B cell surface receptor antagonism is discussed. We review the efficacy of Atacicept, Briobacept and Belimumab in antagonising B lymphocyte stimulator (BLyS) and A proliferation inducing ligand (APRIL), two stimulatory cytokines crucial to B cell survival, growth and function. Two large multicentre randomised controlled trials, BLISS-52 and BLISS-76, have led to FDA approval of Belimumab. Following this breakthrough, other anti-BLyS therapies, Blisibimod and Tabalumab, are currently under Phase III evaluation. Similarly, murine models and Phase I/II trials have demonstrated significant efficacy of Rituximab, Epratuzumab, Briobacept and Atacicept as potential future therapies and we now eagerly await results from Phase III trials. Future research must compare the efficacy of different biologics amongst different patient subpopulations and SLE manifestations, in order to develop clinically and cost effective therapies. PMID:25149393

  5. The hypothalamic-pituitary response in SLE. Regulation of prolactin, growth hormone and cortisol release.

    PubMed

    Rovenský, J; Blazícková, S; Rauová, L; Jezová, D; Koska, J; Lukác, J; Vigas, M

    1998-01-01

    It has been suggested that neuroendocrine regulation plays an important role in the pathogenesis and activation of autoimmune diseases. The aim of this investigation was to clarify the hypothalamic-pituitary response to a well-defined stimulus under standardised conditions in patients with SLE. Plasma concentrations of prolactin (PRL), growth hormone (GH) and cortisol were determined in venous blood drawn through an indwelling cannula during insulin-induced hypoglycaemia (0.1 U/kg b.w., i.v.) in ten patients and in 12 age-, gender- and weight-matched healthy subjects. Basal PRL concentrations were higher in patients vs healthy controls (12 vs 6 ng/ml, P < 0.01), though still within the physiological range. Insulin-induced plasma PRL and GH were significantly increased both in patients and healthy subjects; however, the increments or areas under the curves were not different in the two groups. Plasma cortisol response showed moderate attenuation in patients. Sensitivity of pituitary lactotrothrops to thyrotropin-releasing hormone (TRH) administration (200 microg, i.v.) was the same in patients and control subjects. In SLE patients with low activity of the disease the sensitivity of pituitary PRL release to TRH administration remained unchanged. The hypothalamic response to stress stimulus (hypoglycaemia) was comparable in patients and healthy subjects. PMID:9736325

  6. Patient-reported fatigue and its impact on patients with systemic lupus erythematosus.

    PubMed

    Sterling, Kl; Gallop, K; Swinburn, P; Flood, E; French, A; Al Sawah, S; Iikuni, N; Naegeli, An; Nixon, A

    2014-02-01

    Fatigue is a hallmark symptom of systemic lupus erythematosus (SLE), often associated with flares, side effects of treatment, and extensive organ damage and may have a significant impact on health-related quality of life (HrQoL). To date, the experience of fatigue in patients with SLE is underexplored. This study explored the experience of fatigue in patients with SLE and its impact on their lives through qualitative interviews. This cross-sectional qualitative study was conducted with 22 adult patients with SLE, recruited from two clinical sites in the United States. In-person semi-structured interviews were conducted and thematic analysis was performed focusing on the experience of fatigue in SLE. Results indicated that 21 out of 22 patients experienced fatigue due to SLE. Patients reported that fatigue was variable in nature in terms of both severity and frequency. Fatigue was described as having an impact on multiple aspects of a patient's life: emotions, cognition, work, activities of daily living, leisure activities, social activities, and family activities. Understanding how patients with SLE describe the symptom of fatigue and how it impacts their lives is the key to better understanding how to measure fatigue in clinical studies evaluating new treatments for SLE. PMID:24197552

  7. Association of MIF, but not type I interferon-induced chemokines, with increased disease activity in Asian patients with systemic lupus erythematosus

    PubMed Central

    Connelly, K. L.; Kandane-Rathnayake, R.; Hoi, A.; Nikpour, Mandana; Morand, E. F.

    2016-01-01

    Ethnicity is a key factor impacting on disease severity in SLE, but molecular mechanisms of these associations are unknown. Type I IFN and MIF have each been associated with SLE pathogenesis. We investigated whether increased SLE severity in Asian patients is associated with either MIF or Type I IFN. SLE patients (n = 151) had prospective recording of disease variables. Serum MIF, and a validated composite score of three Type I IFN-inducible chemokines (IFNCK:CCL2, CXCL10, CCL19) were measured. Associations of MIF and IFNCK score with disease activity were assessed, with persistent active disease (PAD) used as a marker of high disease activity over a median 2.6 years follow up. In univariable analysis, MIF, IFNCK score and Asian ethnicity were significantly associated with PAD. Asian ethnicity was associated with higher MIF but not IFNCK score. In multivariable logistic regression analysis, MIF (OR3.62 (95% CI 1.14,11.5), p = 0.03) and Asian ethnicity (OR3.00 (95% CI 1.39,6.46), p < 0.01) but not IFNCK were significantly associated with PAD. These results potentially support an effect of MIF, but not Type I IFN, in heightened SLE disease severity in Asian SLE. The associations of MIF and Asian ethnicity with PAD are at least partly independent. PMID:27453287

  8. Increased plasma fibronectin in patients with systemic lupus erythematosus.

    PubMed

    Nishinarita, S; Yamamoto, M; Takizawa, T; Hayakawa, J; Karasaki, M; Sawada, S

    1990-06-01

    To add to our knowledge of collagen diseases, plasma fibronectin (FN) in patients with systemic lupus erythematosus (SLE) has been measured, and it was determined that the plasma FN value in those with SLE was 454 +/- 36 micrograms/ml, is significantly higher than the FN value in normal subjects (234 +/- 21 micrograms/ml) than that of patients with FN value of patients with active SLE was significantly higher (591 +/- 46 micrograms/ml) that of the patients with non-active SLE (287 +/- 31 micrograms/ml). The plasma FN value of SLE patients was also seen to be associated with the peripheral blood platelet count and with the dose level of the corticosteroid hormone administered to patients. In active SLE patients, it was similarly found that the plasma FN value had a significant correlation with the peripheral blood lymphocyte count and with the dose level of the corticosteroid hormone given to patients. Since the plasma FN value is known to be high in untreated SLE patients, it was felt that the increase of the FN value in SLE patients is not due to the effect of the corticosteroid but to the disease itself. PMID:2202543

  9. Detection of Catalase as a major protein target of the lipid peroxidation product 4-HNE and the lack of its genetic association as a risk factor in SLE

    PubMed Central

    D'souza, Anil; Kurien, Biji T; Rodgers, Rosalie; Shenoi, Jaideep; Kurono, Sadamu; Matsumoto, Hiroyuki; Hensley, Kenneth; Nath, Swapan K; Scofield, R Hal

    2008-01-01

    polymorphism in the promoter region of catalase were non-significant (p > 0.05) in our data, which suggested that this SNP is not associated with SLE. Conclusion Our results indicate that catalase is one of the proteins modified due to oxidative stress. However, catalase may not be a susceptibility gene for SLE. Nonetheless, catalase is oxidatively modified among SLE patients. This suggests a possible role between oxidative modification of catalase and its affects on enzymatic activity in SLE. An oxidatively modified catalase could be one of the reasons for lower enzymatic activity among SLE subjects, which in turn could favor the accumulation of deleterious hydrogen peroxide. Furthermore, HNE-products are potential neoantigens and could be involved in the pathogenesis of SLE. Decrease in catalase activity could affect the oxidant-antioxidant balance. Chronic disturbance of this balance in patients with SLE may work favorably for the premature onset of atherogenesis with severe vascular effect. PMID:18606005

  10. Fish oil N-3 fatty acids increase adiponectin and decrease leptin levels in patients with systemic lupus erythematosus.

    PubMed

    Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-02-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  11. Fish Oil N-3 Fatty Acids Increase Adiponectin and Decrease Leptin Levels in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Lozovoy, Marcell Alysson Batisti; Colado Simão, Andréa Name; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-01-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  12. Serum and Urinary Interleukin-6 in Assessment of Renal Activity in Egyptian Patients with Systemic Lupus Erythematosus

    PubMed Central

    EL-Shereef, Rawhya R.; Lotfi, Ahmed; Abdel-Naeam, Emad A.; Tawfik, Heba

    2016-01-01

    AIM OF THE WORK This study investigates whether serum and urinary interleukin-6 (IL-6) represent an early marker of kidney involvement and assesses the difference between them and renal biopsy in lupus nephritis (LN). PATIENTS AND METHODS A total of 60 systemic lupus erythematosus (SLE) patients were compared to 20 healthy controls. Urinary and serum IL-6 were measured in both patients and controls. In addition, renal biopsy was done prior or shortly after urine and blood sampling; the results were classified according to the International Society of Nephrology/Renal Pathology Society classification of LN by recording the activity score and chronicity score for each sample. RESULTS There was a significant higher level of urinary IL-6 in the SLE patients with biopsy-proven LN than in those without LN and those of the control group. However, no significant difference was reported between the three groups as regards serum IL-6. A strong positive correlation was found between urinary IL-6 and renal disease activity based on the renal SLE disease activity index (SLEDAI) score with no significant correlation regarding the extra renal SLEDAI. Urinary IL-6 was positively correlated with renal biopsy results and with its activity scores but weakly correlated with the chronicity scores. CONCLUSION Urinary IL-6 may provide a simple noninvasive potential marker of disease activity of renal involvement in adult patients with SLE. PMID:26966395

  13. Impaired B cell proliferation by Staphylococcus aureus Cowan 1 in patients with systemic lupus erythematosus.

    PubMed

    Sawada, S; Amaki, S; Takei, M; Karasaki, M; Amaki, I

    1985-09-01

    We examined the proliferative response to Staphylococcus aureus Cowan 1 (SAC) by enriched peripheral blood B cells from patients with systemic lupus erythematosus (SLE). Responses of B cells from patients with active and inactive SLE were significantly lower than those of B cells from normal individuals. Hyporesponsiveness to SAC was not observed in healthy family members of SLE patients. This hyporesponsiveness did not correlate with prednisolone therapy and could not be attributed to serum factors; it did correlate with the presence of suppressor monocytes. However, we could not exclude the possibility of enhanced sensitivity of SLE B lymphocytes to suppressive signals delivered by the monocytes. PMID:3876099

  14. PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical sub-phenotypes.

    PubMed

    Namjou, Bahram; Kim-Howard, Xana; Sun, Celi; Adler, Adam; Chung, Sharon A; Kaufman, Kenneth M; Kelly, Jennifer A; Glenn, Stuart B; Guthridge, Joel M; Scofield, Robert H; Kimberly, Robert P; Brown, Elizabeth E; Alarcón, Graciela S; Edberg, Jeffrey C; Kim, Jae-Hoon; Choi, Jiyoung; Ramsey-Goldman, Rosalind; Petri, Michelle A; Reveille, John D; Vilá, Luis M; Boackle, Susan A; Freedman, Barry I; Tsao, Betty P; Langefeld, Carl D; Vyse, Timothy J; Jacob, Chaim O; Pons-Estel, Bernardo; Niewold, Timothy B; Moser Sivils, Kathy L; Merrill, Joan T; Anaya, Juan-Manuel; Gilkeson, Gary S; Gaffney, Patrick M; Bae, Sang-Cheol; Alarcón-Riquelme, Marta E; Harley, John B; Criswell, Lindsey A; James, Judith A; Nath, Swapan K

    2013-01-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7 × 10(-9), OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7 × 10(-5), OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs

  15. PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

    PubMed Central

    Adler, Adam; Chung, Sharon A.; Kaufman, Kenneth M.; Kelly, Jennifer A.; Glenn, Stuart B.; Guthridge, Joel M.; Scofield, Robert H.; Kimberly, Robert P.; Brown, Elizabeth E.; Alarcón, Graciela S.; Edberg, Jeffrey C.; Kim, Jae-Hoon; Choi, Jiyoung; Ramsey-Goldman, Rosalind; Petri, Michelle A.; Reveille, John D.; Vilá, Luis M.; Boackle, Susan A.; Freedman, Barry I.; Tsao, Betty P.; Langefeld, Carl D.; Vyse, Timothy J.; Jacob, Chaim O.; Pons-Estel, Bernardo; Niewold, Timothy B.; Moser Sivils, Kathy L.; Merrill, Joan T.; Anaya, Juan-Manuel; Gilkeson, Gary S.; Gaffney, Patrick M.; Bae, Sang-Cheol; Alarcón-Riquelme, Marta E.; Harley, John B.; Criswell, Lindsey A.; James, Judith A.; Nath, Swapan K.

    2013-01-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7×10−9, OR = 1.40 (95% CI = 1.25–1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67–0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7×10−5, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with

  16. B lymphocyte activation by insoluble anti-mu antibodies in patients with systemic lupus erythematosus.

    PubMed Central

    Becker, H; Schauer, U; Helmke, K

    1986-01-01

    In order to study the capacity of anti-immunoglobulin (Ig) antibodies to induce proliferative responses in peripheral blood mononuclear cells (PBC) from patients with systemic lupus erythematosus (SLE), anti-mu coupled to Sepharose beads (anti-mu) was used as a polyclonal activator. In 18 patients, a strong proliferative response was associated with inactive disease, and the response was lower in clinical active disease (P less than 0.02). An inverse correlation could also be observed in six patients who were studied longitudinally (P less than 0.01). These results indicate that anti-mu responsiveness is closely related to disease activity in SLE. In addition, sequential data obtained from two patients during an early stage of clinical deterioration suggest that a low anti-mu response might be an early indicator of a clinical relapse. In the patients investigated, the anti-mu response was not correlated with the response to pokeweed mitogen (PWM), or with the quantity of B cells. When T cell depleted cell fractions were studied, marked increases in the proliferative responses to anti-mu were observed in some patients. These studies suggest that the response to anti-mu might be modified by T cells to a variable extent in patients with SLE. PMID:3102135

  17. SLE presenting as multiple hemorrhagic complications.

    PubMed

    Abdulla, M C; Alungal, J; Hashim, S; Ali, M M; Musambil, M

    2015-09-01

    A 24 year old female with hereditary spastic paraplegia presented with intermittent headache for one year. She also had lower abdominal pain and vomiting for two months. She was pale, had icterus and mild splenomegaly. On diagnostic evaluation she was found to have hemolytic anemia, thrombocytopenia and bilateral adrenal, subdural, soft tissue (scalp and orbit) hemorrhages due to systemic lupus erythematosus (SLE). However, antiphospholipid syndrome (APS) antibodies were negative. Bilateral adrenal hemorrhage without associated APS is a rare phenomenon in SLE. We describe a case of SLE presenting with sequence of rare hemorrhagic complications in concert. PMID:25716420

  18. A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE

    PubMed Central

    Sandling, Johanna K; Garnier, Sophie; Sigurdsson, Snaevar; Wang, Chuan; Nordmark, Gunnel; Gunnarsson, Iva; Svenungsson, Elisabet; Padyukov, Leonid; Sturfelt, Gunnar; Jönsen, Andreas; Bengtsson, Anders A; Truedsson, Lennart; Eriksson, Catharina; Rantapää-Dahlqvist, Solbritt; Mälarstig, Anders; Strawbridge, Rona J; Hamsten, Anders; Criswell, Lindsey A; Graham, Robert R; Behrens, Timothy W; Eloranta, Maija-Leena; Alm, Gunnar; Rönnblom, Lars; Syvänen, Ann-Christine

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (Pmeta=0.00010 and Pmeta=0.00040, respectively). STAT1 was also associated with SLE in this cohort (Pmeta=3.3 × 10−5), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis. PMID:21179067

  19. Association of PPP2CA polymorphisms with SLE susceptibility in multiple ethnic groups

    PubMed Central

    Tan, Wenfeng; Sunahori, Katsue; Zhao, Jian; Deng, Yun; Kaufman, Kenneth M.; Kelly, Jennifer A.; Langefeld, Carl D.; Williams, Adrienne H.; Comeau, Mary E.; Ziegler, Julie T.; Marion, Miranda C.; Bae, Sang-Cheol; Lee, Joo Hyun; Lee, Ji-Seon; Chang, Deh-Ming; Song, Yeong Wook; Yu, Chack-Yung; Kimberly, Robert P.; Edberg, Jeffrey C.; Brown, Elizabeth E.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Vilá, Luis M.; Reveille, John D.; Alarcón-Riquelme, Marta E.; Harley, John B.; Boackle, Susan A.; Stevens, Anne M.; Scofield, R. Hal; Merrill, Joan T.; Freedman, Barry I.; Anaya, Juan-Manuel; Criswell, Lindsey A.; Jacob, Chaim O.; Vyse, Timothy J.; Niewold, Timothy B.; Gaffney, Patrick M.; Moser, Kathy L.; Gilkeson, Gary S.; Kamen, Diane L.; James, Judith A.; Grossman, Jennifer M.; Hahn, Bevra H.; Tsokos, George C.; Tsao, Betty P.

    2011-01-01

    Objective T cells from patients with SLE express increased amounts of PP2Ac which contribute to decreased production of IL-2. Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study consisting of 8,695 SLE cases and 7,308 controls from four different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across the PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time PCR. Results A 32-kb haplotype comprised of multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans (HA), European Americans (EA) and Asians but not in African-Americans (AA). Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, EA and HA populations (pmeta=3.8×10−7, OR=1.3[1.14–1.31]). In EA, the largest ethnic dataset, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-dsDNA and anti-RNP antibodies. PPP2CA expression was approximately 2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying GG genotype (p = 0.008). Conclusion Our data provide the first evidence for an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in EA, HA and Asians. PMID:21590681

  20. Systemic Lupus Erythematosus (SLE) (Beyond the Basics)

    MedlinePlus

    ... with medicine, and an exercise program can improve energy levels. (See 'Exercise' below.) Weight changes — SLE can ... ill can cause you to lose muscle and energy quickly. A separate article discusses how to incorporate ...

  1. Molecular Characterization of Circulating Plasma Cells in Patients with Active Systemic Lupus Erythematosus

    PubMed Central

    Lugar, Patricia L.; Love, Cassandra; Grammer, Amrie C.; Dave, Sandeep S.; Lipsky, Peter E.

    2012-01-01

    Systemic lupus erythematosus (SLE) is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC). The molecular characteristics and nature of circulating PC and B cells in SLE have not been completely characterized. Microarray analysis of gene expression was used to characterize circulating PC in subjects with active SLE. Flow cytometry was used to sort PC and comparator B cell populations from active SLE blood, normal blood and normal tonsil. The gene expression profiles of the sorted B cell populations were then compared. SLE PC exhibited a similar gene expression signature as tonsil PC. The differences in gene expression between SLE PC and normal tonsil PC and tonsil plasmablasts (PB) suggest a mature Ig secreting cell phenotype in the former population. Despite this, SLE PC differed in expression of about half the genes from previously published gene expression profiles of normal bone marrow PC, indicating that these cells had not achieved a fully mature status. Abnormal expression of several genes, including CXCR4 and S1P1, suggests a mechanism for the persistence of SLE PC in the circulation. All SLE B cell populations revealed an interferon (IFN) gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells. These data indicate that SLE PC are a unique population of Ig secreting cells with a gene expression profile indicative of a mature, but not fully differentiated phenotype. PMID:23028528

  2. Management considerations for childhood-onset systemic lupus erythematosus patients and implications on therapy.

    PubMed

    Silva, Clovis Artur; Aikawa, Nadia Emi; Pereira, Rosa Maria Rodrigues; Campos, Lucia Maria Arruda

    2016-01-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a chronic inflammatory and autoimmune disease that may involve various organs and systems. This narrative review focuses on the recent evidence relating to cSLE management. The general management considerations of cSLE patients require the use of validated classification criteria, disease and health-related quality of life tools evaluation, as well as assessments of lupus nephritis biomarkers and cSLE quality indicators. The drug treatment for cSLE patients includes general supportive care and immunosuppressive therapy. Important implications on cSLE therapy are also updated such as infection, vaccination, infertility, pregnancy, contraception, dyslipidemia, physical activity, cancer, bone health, drug pharmacokinetics, adherence, academic outcomes, transition to adult care and cumulative organ damage. PMID:26589476

  3. Gene expression in human lupus: bone marrow differentiates active from inactive patients and displays apoptosis and granulopoiesis signatures

    PubMed Central

    Nakou, Magdalene; Knowlton, Nicholas; Frank, Mark B.; Bertsias, George; Osban, Jeanette; Sandel, Clayton E.; Papadaki, Eleni; Raptopoulou, Amalia; Sidiropoulos, Prodromos; Kritikos, Heraklis; Tassiulas, Ioannis; Centola, Michael; Boumpas, Dimitrios T.

    2009-01-01

    Objective The cells of the immune system originate from the bone marrow (BM), where many of them also mature. To better understand the aberrant immune response in systemic lupus erythematosus (SLE), we examined the BM in lupus patients using DNA microarrays and compared it to the peripheral blood (PB). Patients and Methods Bone marrow mononuclear cells (BMMCs) from 20 SLE patients (11 with active disease and 9 with inactive disease) and peripheral blood mononuclear cells (PBMCs) from 27 patients (16 active/ 11 inactive); BMMCs and PBMCs from 7 healthy individuals and 3 osteoarthritis patients served as controls. Samples were analyzed on genome-scale microarrays with 21,329 genes represented. Results We found 102 differentially expressed genes between patients’ and controls’ BMMCs (unpaired student t-test), involved in various biologic processes; 53 of them are involved in major networks including cell death, growth, signaling and proliferation. Comparative analysis between BM and PB of patients identified 88 genes differentially expressed; 61 out of 88 participate in cell growth and differentiation, cellular movement and morphology, immune response and other hematopoietic cell functions. Unsupervised clustering of highly expressed genes revealed two major SLE patient clusters (active and inactive) in BM, but not in PB. The upregulated genes in the bone marrow of active patients included genes involved in cell death and granulopoiesis. Conclusion Microarray analysis of the bone marrow differentiates active from inactive lupus patients and provides further evidence for the role of apoptosis and granulocytes in the pathogenesis of the disease. PMID:18975309

  4. Evaluation of PBMC Distribution and TLR9 Expression in Patients with Systemic Lupus Erythematosus.

    PubMed

    Mortezagholi, Sahar; Babaloo, Zohreh; Rahimzadeh, Parisa; Ghaedi, Mojgan; Namdari, Hayedeh; Assar, Shirin; Azimi Mohamadabadi, Maryam; Salehi, Eisa

    2016-06-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which results in damage to various organs. Some animal studies have revealed that activation of Toll-like receptors (TLRs) is important in the pathogenesis of SLE. In the present study, the percentage of different immune cell subsets in 35 SLE patients and 38 control subjects was analyzed by flow cytometry. We also assessed the expression of TLR9 in the population of peripheral blood mononuclear cells (PBMCs) including T lymphocytes (CD4+ and CD8+), B lymphocytes (CD19+), NK cells (CD56+) and monocytes (CD14+) in SLE patients and healthy controls. The results showed that the percentage of CD8+ T lymphocytes and CD14+ monocytes were significantly higher (p˂0.001) in the SLE patients than the healthy control subjects. Moreover, the percentage of CD56+ NK cells were significantly lower in the SLE patients than the healthy control subjects (p=0.001). The findings indicated that the expression of TLR9 was significantly higher in CD4+ and CD8+ T lymphocytes and CD19+ B lymphocytes of SLE patients than in control subjects (all p˂0.05). The difference in TLR9 expression are involved in pathogenesis of the SLE, hence it can be used as an indicator for SLE diagnosis. PMID:27424138

  5. Induction of inflammatory and immune responses by HMGB1–nucleosome complexes: implications for the pathogenesis of SLE

    PubMed Central

    Urbonaviciute, Vilma; Fürnrohr, Barbara G.; Meister, Silke; Munoz, Luis; Heyder, Petra; De Marchis, Francesco; Bianchi, Marco E.; Kirschning, Carsten; Wagner, Hermann; Manfredi, Angelo A.; Kalden, Joachim R.; Schett, Georg; Rovere-Querini, Patrizia; Herrmann, Martin; Voll, Reinhard E.

    2008-01-01

    Autoantibodies against double-stranded DNA (dsDNA) and nucleosomes represent a hallmark of systemic lupus erythematosus (SLE). However, the mechanisms involved in breaking the immunological tolerance against these poorly immunogenic nuclear components are not fully understood. Impaired phagocytosis of apoptotic cells with consecutive release of nuclear antigens may contribute to the immune pathogenesis. The architectural chromosomal protein and proinflammatory mediator high mobility group box protein 1 (HMGB1) is tightly attached to the chromatin of apoptotic cells. We demonstrate that HMGB1 remains bound to nucleosomes released from late apoptotic cells in vitro. HMGB1–nucleosome complexes were also detected in plasma from SLE patients. HMGB1-containing nucleosomes from apoptotic cells induced secretion of interleukin (IL) 1β, IL-6, IL-10, and tumor necrosis factor (TNF) α and expression of costimulatory molecules in macrophages and dendritic cells (DC), respectively. Neither HMGB1-free nucleosomes from viable cells nor nucleosomes from apoptotic cells lacking HMGB1 induced cytokine production or DC activation. HMGB1-containing nucleosomes from apoptotic cells induced anti-dsDNA and antihistone IgG responses in a Toll-like receptor (TLR) 2–dependent manner, whereas nucleosomes from living cells did not. In conclusion, HMGB1–nucleosome complexes activate antigen presenting cells and, thereby, may crucially contribute to the pathogenesis of SLE via breaking the immunological tolerance against nucleosomes/dsDNA. PMID:19064698

  6. ATAC-seq on biobanked specimens defines a unique chromatin accessibility structure in naïve SLE B cells

    PubMed Central

    Scharer, Christopher D.; Blalock, Emily L.; Barwick, Benjamin G.; Haines, Robert R.; Wei, Chungwen; Sanz, Ignacio; Boss, Jeremy M.

    2016-01-01

    Biobanking is a widespread practice for storing biological samples for future studies ranging from genotyping to RNA analysis. However, methods that probe the status of the epigenome are lacking. Here, the framework for applying the Assay for Transposase Accessible Sequencing (ATAC-seq) to biobanked specimens is described and was used to examine the accessibility landscape of naïve B cells from Systemic Lupus Erythematosus (SLE) patients undergoing disease flares. An SLE specific chromatin accessibility signature was identified. Changes in accessibility occurred at loci surrounding genes involved in B cell activation and contained motifs for transcription factors that regulate B cell activation and differentiation. These data provide evidence for an altered epigenetic programming in SLE B cells and identify loci and transcription factor networks that potentially impact disease. The ability to determine the chromatin accessibility landscape and identify cis-regulatory elements has broad application to studies using biorepositories and offers significant advantages to improve the molecular information obtained from biobanked samples. PMID:27249108

  7. ATAC-seq on biobanked specimens defines a unique chromatin accessibility structure in naïve SLE B cells.

    PubMed

    Scharer, Christopher D; Blalock, Emily L; Barwick, Benjamin G; Haines, Robert R; Wei, Chungwen; Sanz, Ignacio; Boss, Jeremy M

    2016-01-01

    Biobanking is a widespread practice for storing biological samples for future studies ranging from genotyping to RNA analysis. However, methods that probe the status of the epigenome are lacking. Here, the framework for applying the Assay for Transposase Accessible Sequencing (ATAC-seq) to biobanked specimens is described and was used to examine the accessibility landscape of naïve B cells from Systemic Lupus Erythematosus (SLE) patients undergoing disease flares. An SLE specific chromatin accessibility signature was identified. Changes in accessibility occurred at loci surrounding genes involved in B cell activation and contained motifs for transcription factors that regulate B cell activation and differentiation. These data provide evidence for an altered epigenetic programming in SLE B cells and identify loci and transcription factor networks that potentially impact disease. The ability to determine the chromatin accessibility landscape and identify cis-regulatory elements has broad application to studies using biorepositories and offers significant advantages to improve the molecular information obtained from biobanked samples. PMID:27249108

  8. Cold agglutinin-induced haemolysis in association with antinuclear antibody-negative SLE.

    PubMed

    Chaubey, Vinod K; Chhabra, Lovely

    2013-01-01

    Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease associated with several autoantibodies targeted to nuclear and cytoplasmic antigens. Serum antinuclear antibody (ANA) is considered an important diagnostic marker of SLE. However, 2-3% of patients with typical clinical picture of SLE may have persistently negative ANA tests. Autoimmune haemolytic anaemia (AIHA) in SLE is usually mediated by warm IgG anti-erythrocyte antibodies. Our report describes a female patient who presented with clinical manifestations of SLE including photosensitivity, joint pains and AIHA. Further workup revealed high cold IgM agglutinin titres. A comprehensive workup for infectious aetiologies was negative. Autoimmune studies revealed negative ANA, but positive anti-double-stranded DNA and antiphospholipid antibodies. Lymphoproliferative disorder was excluded by imaging studies. Initial treatment with steroids proved of little benefit; however, rituximab resulted in significant clinical improvement. To the best of our knowledge, this is perhaps the first report of ANA-negative SLE presenting with cold AIHA. PMID:23761498

  9. Cold agglutinin-induced haemolysis in association with antinuclear antibody-negative SLE

    PubMed Central

    Chaubey, Vinod K; Chhabra, Lovely

    2013-01-01

    Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease associated with several autoantibodies targeted to nuclear and cytoplasmic antigens. Serum antinuclear antibody (ANA) is considered an important diagnostic marker of SLE. However, 2–3% of patients with typical clinical picture of SLE may have persistently negative ANA tests. Autoimmune haemolytic anaemia (AIHA) in SLE is usually mediated by warm IgG anti-erythrocyte antibodies. Our report describes a female patient who presented with clinical manifestations of SLE including photosensitivity, joint pains and AIHA. Further workup revealed high cold IgM agglutinin titres. A comprehensive workup for infectious aetiologies was negative. Autoimmune studies revealed negative ANA, but positive anti-double-stranded DNA and antiphospholipid antibodies. Lymphoproliferative disorder was excluded by imaging studies. Initial treatment with steroids proved of little benefit; however, rituximab resulted in significant clinical improvement. To the best of our knowledge, this is perhaps the first report of ANA-negative SLE presenting with cold AIHA. PMID:23761498

  10. Clearance Deficiency and Cell Death Pathways: A Model for the Pathogenesis of SLE

    PubMed Central

    Mahajan, Aparna; Herrmann, Martin; Muñoz, Luis E.

    2016-01-01

    Alterations of cell death pathways, including apoptosis and the neutrophil specific kind of death called NETosis, can represent a potential source of autoantigens. Defects in the clearance of apoptotic cells may be responsible for the initiation of systemic autoimmunity in several chronic inflammatory diseases, including systemic lupus erythematosus (SLE). Autoantigens are released mainly from secondary necrotic cells because of a defective clearance of apoptotic cells or an inefficient degradation of DNA-containing neutrophil extracellular traps (NETs). These modified autoantigens are presented by follicular dendritic cells to autoreactive B cells in germinal centers of secondary lymphoid organs. This results in the loss of self-tolerance and production of autoantibodies, a unifying feature of SLE. Immune complexes (IC) are formed from autoantibodies bound to uncleared cellular debris in blood or tissues. Clearance of IC by blood phagocytes, macrophages, and dendritic cells leads to proinflammatory cytokine secretion. In particular, plasmacytoid dendritic cells produce high amounts of interferon-α upon IC uptake, thereby contributing to the interferon signature of patients with SLE. The clearance of antinuclear IC via Fc-gamma receptors is considered a central event in amplifying inflammatory immune responses in SLE. Along with this, the accumulation of cell remnants represents an initiating event of the etiology, while the subsequent generation of autoantibodies against nuclear antigens (including NETs) results in the perpetuation of inflammation and tissue damage in patients with SLE. Here, we discuss the implications of defective clearance of apoptotic cells and NETs in the development of clinical manifestations in SLE. PMID:26904025

  11. Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE.

    PubMed

    Biesen, R; Rose, T; Hoyer, B F; Alexander, T; Hiepe, F

    2016-07-01

    Systemic lupus erythematosus (SLE) can be a mysterious disease, presenting with extremely divergent clinical phenotypes. Already, biomarkers are very helpful tools for diagnosis, assessment and monitoring of disease activity, differential diagnosis of clinical manifestations, prediction of the disease course and stratified therapy, and they hold the key to personalized medicine in SLE. We summarize the clinical information that can only be supplied by autoantibodies, complement components and interferon biomarkers in this diverse disease. PMID:27252258

  12. Comparison of the scanning linear estimator (SLE) and ROI methods for quantitative SPECT imaging

    NASA Astrophysics Data System (ADS)

    Könik, Arda; Kupinski, Meredith; Hendrik Pretorius, P.; King, Michael A.; Barrett, Harrison H.

    2015-08-01

    In quantitative emission tomography, tumor activity is typically estimated from calculations on a region of interest (ROI) identified in the reconstructed slices. In these calculations, unpredictable bias arising from the null functions of the imaging system affects ROI estimates. The magnitude of this bias depends upon the tumor size and location. In prior work it has been shown that the scanning linear estimator (SLE), which operates on the raw projection data, is an unbiased estimator of activity when the size and location of the tumor are known. In this work, we performed analytic simulation of SPECT imaging with a parallel-hole medium-energy collimator. Distance-dependent system spatial resolution and non-uniform attenuation were included in the imaging simulation. We compared the task of activity estimation by the ROI and SLE methods for a range of tumor sizes (diameter: 1-3 cm) and activities (contrast ratio: 1-10) added to uniform and non-uniform liver backgrounds. Using the correct value for the tumor shape and location is an idealized approximation to how task estimation would occur clinically. Thus we determined how perturbing this idealized prior knowledge impacted the performance of both techniques. To implement the SLE for the non-uniform background, we used a novel iterative algorithm for pre-whitening stationary noise within a compact region. Estimation task performance was compared using the ensemble mean-squared error (EMSE) as the criterion. The SLE method performed substantially better than the ROI method (i.e. EMSE(SLE) was 23-174 times lower) when the background is uniform and tumor location and size are known accurately. The variance of the SLE increased when a non-uniform liver texture was introduced but the EMSE(SLE) continued to be 5-20 times lower than the ROI method. In summary, SLE outperformed ROI under almost all conditions that we tested.

  13. Comparison of the scanning linear estimator (SLE) and ROI methods for quantitative SPECT imaging.

    PubMed

    Könik, Arda; Kupinski, Meredith; Pretorius, P Hendrik; King, Michael A; Barrett, Harrison H

    2015-08-21

    In quantitative emission tomography, tumor activity is typically estimated from calculations on a region of interest (ROI) identified in the reconstructed slices. In these calculations, unpredictable bias arising from the null functions of the imaging system affects ROI estimates. The magnitude of this bias depends upon the tumor size and location. In prior work it has been shown that the scanning linear estimator (SLE), which operates on the raw projection data, is an unbiased estimator of activity when the size and location of the tumor are known. In this work, we performed analytic simulation of SPECT imaging with a parallel-hole medium-energy collimator. Distance-dependent system spatial resolution and non-uniform attenuation were included in the imaging simulation. We compared the task of activity estimation by the ROI and SLE methods for a range of tumor sizes (diameter: 1-3 cm) and activities (contrast ratio: 1-10) added to uniform and non-uniform liver backgrounds. Using the correct value for the tumor shape and location is an idealized approximation to how task estimation would occur clinically. Thus we determined how perturbing this idealized prior knowledge impacted the performance of both techniques. To implement the SLE for the non-uniform background, we used a novel iterative algorithm for pre-whitening stationary noise within a compact region. Estimation task performance was compared using the ensemble mean-squared error (EMSE) as the criterion. The SLE method performed substantially better than the ROI method (i.e. EMSE(SLE) was 23-174 times lower) when the background is uniform and tumor location and size are known accurately. The variance of the SLE increased when a non-uniform liver texture was introduced but the EMSE(SLE) continued to be 5-20 times lower than the ROI method. In summary, SLE outperformed ROI under almost all conditions that we tested. PMID:26247228

  14. Systemic lupus erythematosus in patients with sickle cell disease.

    PubMed

    Appenzeller, Simone; Fattori, Andre; Saad, Sarita T; Costallat, Lilian T L

    2008-03-01

    Sickle cell disease (SCD) is a prevalent genetic disorder that includes sickle cell anemia (hemoglobin SS), hemoglobin SC, and hemoglobin Sb-thalassemia. Patients with SCD present with a defective activation of the alternate pathway of the complement system that increases the risk of capsulate bacteria infection and failure to eliminate antigens, predisposing these patients to autoimmune diseases. The authors describe three patients with SCD that developed systemic lupus erythematosus (SLE). In all patients, SLE diagnosis was delayed because symptoms were initially attributable to SCD. Physicians should be alerted to the possible development of SLE in patients with SCD to not delay the diagnosis and start appropriate treatment. PMID:18000698

  15. Probable systemic lupus erythematosus with cell-bound complement activation products (CB-CAPS).

    PubMed

    Lamichhane, D; Weinstein, A

    2016-08-01

    Complement activation is a key feature of systemic lupus erythematosus (SLE). Detection of cell-bound complement activation products (CB-CAPS) occurs more frequently than serum hypocomplementemia in definite lupus. We describe a patient with normocomplementemic probable SLE who did not fulfill ACR classification criteria for lupus, but the diagnosis was supported by the presence of CB-CAPS. PMID:26911153

  16. Serum Thiols as a Biomarker of Disease Activity in Lupus Nephritis

    PubMed Central

    Lalwani, Pritesh; de Souza, Giselle Katiane Bonfim Bacelar; de Lima, Domingos Savio Nunes; Passos, Luiz Fernando Souza; Boechat, Antonio Luiz; Lima, Emerson Silva

    2015-01-01

    Lupus Nephritis (LN) develops in more than half of the Systemic Lupus Erythematous (SLE) patients. However, lack of reliable, specific biomarkers for LN hampers clinical management of patients and impedes development of new therapeutics. The goal of this study was to investigate whether oxidative stress biomarkers in patients with SLE is predictive of renal pathology. Serum biochemical and oxidative stress markers were measured in patients with inactive lupus, active lupus with and without nephritis and compared to healthy control group. To assess the predictive performance of biomarkers, Receiver Operating Characteristic (ROC) curves were constructed and cut-offs were used to identify SLE patients with nephritis. We observed an increased oxidative stress response in all SLE patients compared to healthy controls. Among the several biomarkers tested, serum thiols had a significant inverse association with SLE Disease Activity Index (SLEDAI). Interestingly, thiols were able too aptly differentiate between SLE patients with and without renal pathology, and serum thiol levels were not affected by immunosuppressive drug therapy. The decreased thiols in SLE correlated significantly with serum creatinine and serum C3 levels. Further retrospective evaluation using serum creatinine or C3 levels in combination with thiol’s cutoff values from ROC analysis, we could positively predict chronicity of renal pathology in SLE patients. In summary, serum thiols emerge as an inexpensive and reliable indicator of LN, which may not only help in early identification of renal pathology but also aid in the therapeutic management of the disease, in developing countries with resource poor settings. PMID:25799079

  17. Loss of Immune Tolerance Is Controlled by ICOS in Sle1 Mice.

    PubMed

    Mittereder, Nanette; Kuta, Ellen; Bhat, Geetha; Dacosta, Karma; Cheng, Lily I; Herbst, Ronald; Carlesso, Gianluca

    2016-07-15

    ICOS, a member of the CD28 family, represents a key molecule that regulates adaptive responses to foreign Ags. ICOS is prominently expressed on T follicular helper (TFH) cells, a specialized CD4(+) T cell subset that orchestrates B cell differentiation within the germinal centers and humoral response. However, the contribution of ICOS and TFH cells to autoantibody profiles under pathological conditions has not been thoroughly investigated. We used the Sle1 lupus-prone mouse model to examine the role of ICOS in the expansion and function of pathogenic TFH cells. Genetic deletion of ICOS impacted the expansion of TFH cells in B6.Sle1 mice and inhibited the differentiation of B lymphocytes into plasma cells. The phenotypic changes observed in B6.Sle1-ICOS-knockout mice were also associated with a significant reduction in class-switched IgG, and anti-nucleosomal IgG-secreting B cells compared with B6.Sle1 animals. The level of vascular cell adhesion protein 1, a molecule that was shown to be elevated in patients with SLE and in lupus models, was also increased in an ICOS-dependent manner in Sle1 mice and correlated with autoantibody levels. The elimination of ICOS-expressing CD4(+) T cells in B6.Sle1 mice, using a glyco-engineered anti-ICOS-depleting Ab, resulted in a significant reduction in anti-nucleosomal autoantibodies. Our results indicate that ICOS regulates the ontogeny and homeostasis of B6.Sle1 TFH cells and influences the function of TFH cells during aberrant germinal center B cell responses. Therapies targeting the ICOS signaling pathway may offer new opportunities for the treatment of lupus and other autoimmune diseases. PMID:27296665

  18. Loss of Immune Tolerance Is Controlled by ICOS in Sle1 Mice

    PubMed Central

    Mittereder, Nanette; Kuta, Ellen; Bhat, Geetha; Dacosta, Karma; Cheng, Lily I.; Herbst, Ronald

    2016-01-01

    ICOS, a member of the CD28 family, represents a key molecule that regulates adaptive responses to foreign Ags. ICOS is prominently expressed on T follicular helper (TFH) cells, a specialized CD4+ T cell subset that orchestrates B cell differentiation within the germinal centers and humoral response. However, the contribution of ICOS and TFH cells to autoantibody profiles under pathological conditions has not been thoroughly investigated. We used the Sle1 lupus-prone mouse model to examine the role of ICOS in the expansion and function of pathogenic TFH cells. Genetic deletion of ICOS impacted the expansion of TFH cells in B6.Sle1 mice and inhibited the differentiation of B lymphocytes into plasma cells. The phenotypic changes observed in B6.Sle1-ICOS–knockout mice were also associated with a significant reduction in class-switched IgG, and anti-nucleosomal IgG-secreting B cells compared with B6.Sle1 animals. The level of vascular cell adhesion protein 1, a molecule that was shown to be elevated in patients with SLE and in lupus models, was also increased in an ICOS-dependent manner in Sle1 mice and correlated with autoantibody levels. The elimination of ICOS-expressing CD4+ T cells in B6.Sle1 mice, using a glyco-engineered anti-ICOS–depleting Ab, resulted in a significant reduction in anti-nucleosomal autoantibodies. Our results indicate that ICOS regulates the ontogeny and homeostasis of B6.Sle1 TFH cells and influences the function of TFH cells during aberrant germinal center B cell responses. Therapies targeting the ICOS signaling pathway may offer new opportunities for the treatment of lupus and other autoimmune diseases. PMID:27296665

  19. Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

    PubMed Central

    2013-01-01

    Introduction Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. Methods Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. Results Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. Conclusions The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE. PMID:23497733

  20. Endocan Levels and Subclinical Atherosclerosis in Patients With Systemic Lupus Erythematosus.

    PubMed

    Icli, Abdullah; Cure, Erkan; Cure, Medine Cumhur; Uslu, Ali Ugur; Balta, Sevket; Mikhailidis, Dimitri P; Ozturk, Cengiz; Arslan, Sevket; Sakız, Davut; Sahin, Muhammed; Kucuk, Adem

    2016-09-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. A major cause of morbidity and mortality in SLE is accelerated atherosclerosis. Endothelial-specific molecule 1 (endocan) is a potential predictor of vascular events and is expressed in response to inflammatory cytokines in endothelial cells. We investigated the relationship between endocan and carotid intima-media thickness (cIMT) as a marker of early atherosclerosis. We included 44 women with SLE and 44 healthy women as controls. Disease severity of SLE was evaluated using the SLE Disease Activity Index. Endocan, C-reactive protein, erythrocyte sedimentation rate (ESR), and lipid panel were measured. The cIMT was 0.70 (range: 0.45-1.20) mm in patients with SLE and 0.40 (0.25-0.60) mm in controls (P < .001). Endocan value was 1.6 ± 0.9 ng/mL in controls and 2.2 ± 1.0 ng/mL in patients with SLE (P = .014). Endocan levels were positively correlated with cIMT (r = .469, P < .001), body mass index (r = .373, P = .013), and ESR (r = .393, P = .008). Endocan level may be associated with subclinical atherosclerosis in SLE. Consequently, endocan levels may be a promising clinical tool for patients with SLE as a guide for preventive strategy. PMID:26614790

  1. Anti-DNA antibodies in SLE

    SciTech Connect

    Voss, E.W.

    1988-01-01

    This book contains 8 chapters. Some of the titles are: Anti-DNA Antibodies in SLE: Historical Perspective; Specificity of Anti-DNA Antibodies in Systemic Lupus Erythematosus; Monoclonial Autoimmune Anti-DNA Antibodies; and Structure--Function Analyses of Anti-DNA Autoantibodies.

  2. Evaluation of SLE Susceptibility Genes in Malaysians

    PubMed Central

    Molineros, Julio E.; Chua, Kek Heng; Sun, Celi; Lian, Lay Hoong; Motghare, Prasenjeet; Kim-Howard, Xana; Nath, Swapan K.

    2014-01-01

    Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH) and Malays (MA)) from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA) using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African). Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (P < 0.05). The strongest signal was at HLA-DRA (PMeta = 9.96 × 10−9; PCH = 6.57 × 10−8, PMA = 6.73 × 10−3); the strongest non-HLA signal occurred at STAT4 (PMeta = 1.67 × 10−7; PCH = 2.88 × 10−6, PMA = 2.99 × 10−3). Most of these genes were associated with B- and T-cell function and signaling pathways. Our exploratory study using high-density fine-mapping suggests that most of the established SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies. PMID:24696779

  3. Correlation of C3d fixing circulating immune complexes with disease activity and clinical parameters in patients with systemic lupus erythematosus.

    PubMed Central

    Sekita, K; Doi, T; Muso, E; Yoshida, H; Kanatsu, K; Hamashima, Y

    1984-01-01

    Using anti-C3d as a solid phase reagent, C3d fixing circulating immune complexes (CIC) were detected in sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, membranous nephropathy and IgA nephropathy. Particularly, sera from SLE showed the highest CIC levels and highest incidence of positivity among these diseases. In the 51 serum samples from 48 patients with SLE we studied, the CIC detected by the anti-C3d assay correlated well (P less than 0.01) with the CIC detected by the solid phase C1q assay, but not with those detected by the conglutinin assay. In addition, the CIC detected by the anti-C3d assay correlated more significantly (P less than 0.001) with disease activity, as well as some clinical parameters (serum anti-dsDNA antibodies, CH50 and C3 levels) than CIC detected by the other two assays of SLE sera. The anti-C3d binding materials were found to be of intermediate (8-19S) and small (7S) sizes in a small number of SLE sera which we analysed. PMID:6608422

  4. Key issues in the management of patients with systemic lupus erythematosus: latest developments and clinical implications

    PubMed Central

    Jordan, Natasha; D’Cruz, David

    2015-01-01

    Systemic lupus erythematous (SLE) is a chronic multisystem disease with significant associated morbidity and mortality. A deeper understanding of the pathogenesis of SLE has led to the development of biologic agents, primarily targeting B cells and others inhibiting costimulatory molecules, type I interferons and cytokines such as interleukin-6. Several of these agents have been studied in clinical trials; some have shown promise while others have yielded disappointing results. Economic and regulatory issues continue to hamper the availability of such therapies for SLE patients. With increasing recognition that recurrent flares of disease activity lead to long-term damage accrual, one of the most important recent developments in patient management has been the concept of treat-to-target in SLE while minimizing patient exposure to excessive corticosteroid and other immunosuppressive therapy. This article reviews these key issues in SLE management, outlining recent developments and clinical implications for patients. PMID:26622325

  5. DNA-hydrolysing activity of IgG antibodies from the sera of patients with schizophrenia

    PubMed Central

    Ermakov, Evgeny A.; Smirnova, Ludmila P.; Parkhomenko, Taisiya A.; Dmitrenok, Pavel S.; Krotenko, Nina M.; Fattakhov, Nikolai S.; Bokhan, Nikolay A.; Semke, Arkadiy V.; Ivanova, Svetlana A.; Buneva, Valentina N.; Nevinsky, Georgy A.

    2015-01-01

    It is believed that damage to the membranes of brain cells of schizophrenia (SCZ) patients induces the formation of autoantigens and autoantibodies. Nevertheless, the importance of immunological changes leading to the loss of tolerance to self-antigens in the genesis of SCZ has not been established. The MALDI mass spectra of the IgG light chains of 20 healthy donors were relatively homogeneous and characterized by one peak with only one maximum. In contrast to the healthy donors, the MALDI mass spectra of IgG light chains corresponding to 20 SCZ patients demonstrated, similarly to 20 autoimmune systemic lupus erythematosus (SLE) patients, two maxima of a comparable intensity. In addition, the MALDI spectra of the IgG light chains of five SLE and four SCZ patients contained a small additional brightly pronounced peak with remarkably lower molecular mass compared with the main one. DNase autoantibodies (abzymes) can be found in the blood of patients with several autoimmune diseases, while the blood of healthy donors or patients with diseases without a significant disturbance of the immune status does not contain DNase abzymes. Here, we present the first analysis of anti-DNA antibodies and DNase abzymes in the sera of SCZ patients. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of SCZ patients. The sera of approximately 30% of SCZ patients displayed a higher content of antibodies (compared with 37% of SLE) interacting with single- and double-stranded DNA compared with healthy donors. Antibodies with DNase activity were revealed in 80% of the patients. These data indicate that some SCZ patients may show signs of typical autoimmune processes to a certain extent. PMID:26382278

  6. Structural integration-based fascial release efficacy in systemic lupus erythematosus (SLE): two case studies.

    PubMed

    Ball, Tanya M

    2011-04-01

    Auto-immune conditions such as Scleroderma and SLE induce fascial sclerosis and fibrosis, with related vascular, lymphatic, neural, joint, and visceral compression. Ensuing ischaemic pain, necrosis, autonomic and immune dysfunction in turn account for much of patients' pain, functional impairment, and psychological distress. Fascial Release Therapy (FRT) is a hands-on therapeutic model focused on restoring postural and functional integrity by addressing fascial imbalance, with hypothesized efficacy for SLE patients in: Two SLE patients who received FRT treatment along KMI® SI methodology, reported improvements to seven symptoms, namely: While 'spontaneous recovery' cannot be ruled out without controls, these anecdotal results support further, broader-based clinical research with stringent evaluation tools to enhance outcome validity. Therapeutic mechanisms may includefascial relaxation as key to decreasing myofascial pain; myofibroblast response to 'stress'; inter- and trans-fascial plane transfer of enhanced 'ease' and 'glide'. Psycho-neuro-immunological factors reversing adverse auto-immune response. PMID:21419363

  7. Activation-induced necroptosis contributes to B-cell lymphopenia in active systemic lupus erythematosus

    PubMed Central

    Fan, H; Liu, F; Dong, G; Ren, D; Xu, Y; Dou, J; Wang, T; Sun, L; Hou, Y

    2014-01-01

    B-cell abnormality including excessive activation and lymphopenia is a central feature of systemic lupus erythematosus (SLE). Although activation threshold, auto-reaction and death of B cells can be affected by intrinsical and/or external signaling, the underlying mechanisms are unclear. Herein, we demonstrate that co-activation of Toll-like receptor 7 (TLR7) and B-cell receptor (BCR) pathways is a core event for the survival/dead states of B cells in SLE. We found that the mortalities of CD19+CD27- and CD19+IgM+ B-cell subsets were increased in the peripheral blood mononuclear cells (PBMCs) of SLE patients. The gene microarray analysis of CD19+ B cells from active SLE patients showed that the differentially expressed genes were closely correlated to TLR7, BCR, apoptosis, necroptosis and immune pathways. We also found that co-activation of TLR7 and BCR could trigger normal B cells to take on SLE-like B-cell characters including the elevated viability, activation and proliferation in the first 3 days and necroptosis in the later days. Moreover, the necroptotic B cells exhibited mitochondrial dysfunction and hypoxia, along with the elevated expression of necroptosis-related genes, consistent with that in both SLE B-cell microarray and real-time PCR verification. Expectedly, pretreatment with the receptor-interacting protein kinase 1 (RIPK1) inhibitor Necrostatin-1, and not the apoptosis inhibitor zVAD, suppressed B-cell death. Importantly, B cells from additional SLE patients also significantly displayed high expression levels of necroptosis-related genes compared with those from healthy donors. These data indicate that co-activation of TLR7 and BCR pathways can promote B cells to hyperactivation and ultimately necroptosis. Our finding provides a new explanation on B-cell lymphopenia in active SLE patients. These data suggest that extrinsic factors may increase the intrinsical abnormality of B cells in SLE patients. PMID:25210799

  8. Incidental retinal vascular occlusions on hydroxychloroquine screening in patients with systemic lupus erythematosus

    PubMed Central

    Bajwa, Asima; Khurana, Gitanjali; Kimpel, Donald; Reddy, Ashvini K

    2015-01-01

    Objective The proportion of patients with systemic lupus erythematosus (SLE) who manifest retinal involvement increases many fold in patients with active systemic disease. The objective of this report is to stress upon the significance of comprehensive ophthalmic assessment of all SLE patients to prevent and manage blinding ocular manifestations of the disease. Methods Retrospective case review. Results Incidental retinal vascular complications seen in patients undergoing baseline hydroxychloroquine screening. Conclusion The purpose of comprehensive ophthalmic screening in SLE patients is twofold. It will aid in the diagnosis and treatment of blinding ocular complications of the disease and monitor hydroxychloroquine macular toxicity. PMID:26064074

  9. Studies on human blood lymphocytes with iC3b (type 3) complement receptors: III. Abnormalities in patients with active systemic lupus erythematosus.

    PubMed Central

    Gray, J D; Lash, A; Bakke, A C; Kitridou, R C; Horwitz, D A

    1987-01-01

    Lymphocytes displaying iC3b (Type 3) complement receptors (CR3) were quantified by flow cytometry in patients with systemic lupus erythematosus. The percentages and absolute numbers were compared to age and sex matched controls. Total CR3+ lymphocytes identified by the monoclonal antibodies OKM1 or Leu 15 were significantly decreased in patients with symptomatic arthritis, serositis or vasculitis and those with lupus nephritis, whereas values for CR3+ lymphocytes in patients with inactive disease were similar to normal donors. The phenotype of CR3+ lymphocytes was markedly different in patients with active SLE. In normals granular lymphocytes bearing Fc receptors for IgG (L cells) comprised two-thirds of CR3+ lymphocytes. However, in SLE this subset was reduced to 20% and there was a corresponding increase in CR3+ lymphocytes co-expressing the T3 marker. Percentages of CR3 T4+ but not CR3+ T8+ lymphocytes were significantly increased in SLE. Although patients with active disease were lymphopenic, absolute numbers of CR3+ lymphocytes co-expressing T cell markers were similar to normal controls. Since L cells are non-specific suppressors of Ig production, the reduction of this subset along with the increase in CR3 T4+ cells could contribute to unregulated antibody production characteristic of SLE. PMID:2955974

  10. Phospholipid base exchange activity in the leukocyte membranes of patients with inflammatory disorders.

    PubMed Central

    Niwa, Y.; Sakane, T.; Ozaki, Y.; Kanoh, T.; Taniguchi, S.

    1987-01-01

    Phospholipid base exchange and cholinephosphotransferase (CPT) and ethanolaminephosphotransferase (EPT) activities were assessed in the membranes of neutrophils or lymphocytes from patients with various inflammatory disorders. Ethanolamine exchange activity was significantly enhanced in both neutrophils and lymphocytes from patients with active Behçet's disease, active systemic lupus erythematosus (SLE), and severe bacterial infections and slightly enhanced in those from patients with active rheumatoid arthritis (RA), compared with healthy controls. No abnormal findings were found in CPT, EPT, or serine or choline base exchange activities in the leukocytes from any of the diseased groups tested or in the ethanolamine exchange activity of patients with severe viral infections and inactive SLE, RA, and Behçet's disease. The authors have recently demonstrated the enhancement of transmethylation and phospholipase A2 activity in human leukocyte membranes at the height of inflammatory disease states, as well as the activation of leukocyte ethanolamine exchange by bioactive stimulants. These data postulate that phosphatidylethanolamine synthesis by the base exchange reaction may be the precursor of transmethylation and its subsequent activation of phospholipase A2, leading to the induction of arachidonic acid cascade. PMID:3034067

  11. Expression of BAFF and BR3 in patients with systemic lupus erythematosus

    PubMed Central

    Duan, J.H.; Jiang, Y.; Mu, H.; Tang, Z.Q.

    2016-01-01

    The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01). The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01). BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01). The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01). The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment. PMID:26840704

  12. Reduced opsonisation of protein A containing Staphylococcus aureus in sera with cryoglobulins from patients with active systemic lupus erythematosus.

    PubMed Central

    Nived, O; Linder, C; Odeberg, H; Svensson, B

    1985-01-01

    Among a total of 41 patients with systemic lupus erythematosus (SLE) 11 of 14 patients with active disease had reduced capacity (p less than 0.05) to opsonify Staphylococcus aureus in undiluted sera, as compared with nine of 27 patients with inactive disease (p less than 0.02). The opsonic reduction in the active patients increased with the number of active organ systems (p less than 0.002). No correlation was found between reduced opsonisation and corticosteroid treatment, or serum concentrations of complement components (C) of the classical pathway, or bacteria-associated activated C3. When the cryoglobulin fraction of immune complexes (IC) was removed, normal opsonic capacity was restored, and the opsonic reduction could be transferred with the cryoglobulins to pooled serum. Increased IC values, as measured by C1q binding assay, were found in conjunction with reduced opsonic capacity (p less than 0.04). Since opsonisation in SLE sera of a protein A deficient strain of S. aureus was normal, reduced S. aureus phagocytosis in SLE sera may be explained by IC binding to staphylococcal protein A. PMID:3872638

  13. Relationship between Serum Level of Interleukin-2 in Patients with Systemic Lupus Erythematosus and Disease Activity in Comparison with Control Group

    PubMed Central

    Aghaei, Mehrdad; Musavi, Sara; Nomali, Mahin

    2014-01-01

    Background: Despite the large number of surveys, there are not any validated biomarkers for SLE disease activity till now. This study aimed to evaluate the relationship between serum level of IL-2 in patients with SLE and disease activity in comparison with control group. Materials and Methods: In this case-control study, 73 patients with lupus and 73 healthy subjects referred to the rheumatology clinic of 5 Azar Hospital in Gorgan (North of Iran).They were studied via convenience sampling during 2011-2012. Blood samples were taken from both groups and serum levels of interleukin -2 measured by Avi Bion Human IL-2 ELISA kit. Serum Level of IL-2 greater than 15 pg/ml defined positive and lesser than this amount defined negative. Disease activity evaluated with SLE disease activity index. Score greater than or equal to three or four defined as active disease. Data analysis conducted by SPSS software (version 16) and by using descriptive statistics and statistical tests. Results: Serum level of IL-2 was positive in 45.2% of sample studied and negative in 54.8% in case group, while in control group, serum level of IL-2 only in 11% of sample studied was positive and in 89% was negative. Statistical analysis indicated a significant relationship between serum level of IL-2 and the SLE disease activity index (p=0.025). Conclusion: This study showed the relationship between serum levels of IL-2 and disease activity, so this biomarker can be used as a clinical indicator for assessing disease activity in patients with SLE. PMID:25177590

  14. Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: a refractory case without lupus activity.

    PubMed

    Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel

    2013-01-01

    The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab. PMID:23473755

  15. Differential Expression of O-Glycans in CD4(+) T Lymphocytes from Patients with Systemic Lupus Erythematosus.

    PubMed

    Ramos-Martínez, Edgar; Lascurain, Ricardo; Tenorio, Eda Patricia; Sánchez-González, Antonio; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Jara-Quezada, Luis J; Chávez-Sánchez, Raúl; Zenteno, Edgar; Blanco-Favela, Francisco

    2016-01-01

    T cells from patients with systemic lupus erythematosus (SLE) show a decreased activation threshold and increased apoptosis. These processes seem to be regulated by glycosylated molecules on the T cell surface. Here, we determined through flow cytometry the expression of mucin-type O-glycans on T helper cells in peripheral blood mononuclear cells (PBMC) from 23 SLE patients and its relation with disease activity. We used lectins specific for the disaccharide Gal-GalNAc, such as Amaranthus leucocarpus lectin (ALL), Artocarpus integrifolia lectin (jacalin) and Arachis hypogaea lectin (peanut agglutinin, PNA), as well as lectins for sialic acid such as Sambucus nigra agglutinin (SNA) and Maakia amurensis agglutinin (MAA). The results showed that ALL, but not jacalin or PNA, identified significant differences in O-glycan expression on T helper cells from active SLE patients (n = 10). Moreover, an inverse correlation was found between the frequency of T helper cells recognized by ALL and SLE Disease Activity Index (SLEDAI) score in SLE patients. In contrast, SNA and MAA lectins did not identify any differences between CD4(+) T cells from SLE patients. There was no difference in the recognition by ALL on activated T helper cells and T regulatory (Treg) cells. Our findings point out that activation of SLE disease diminishes the expression of O-glycans in T helper cells; ALL could be considered as a marker to determine activity of the disease. PMID:27600584

  16. Evaluation of the Patient Acceptable Symptom State (PASS) in Italian Patients Affected by Systemic Lupus Erythematosus: Association with Disease Activity Indices

    PubMed Central

    Conti, Fabrizio; Ceccarelli, Fulvia; Massaro, Laura; Pacucci, Viviana A.; Miranda, Francesca; Truglia, Simona; Cipriano, Enrica; Martinelli, Francesco; Leccese, Ilaria; Spinelli, Francesca Romana; Alessandri, Cristiano; Perricone, Carlo; Valesini, Guido

    2013-01-01

    Objectives The aim of this study was to evaluate the discriminant capability of the patient acceptable symptom state (PASS) according to disease activity, in a cohort of Italian patients affected by systemic Lupus erythematosus (SLE). Methods Consecutive SLE patients were enrolled. At each visit, the patients underwent a complete physical examination and the clinical/laboratory data were collected in a standardized, computerized, and electronically-filled form. The evaluation of serum complement C3 and C4 levels and determination of autoantibodies was obtained. Disease activity was assessed with the SLEDAI-2K and ECLAM, while chronic damage was measured with the SLICC. Finally, PASS was assessed in all patients by asking to answer yes or no to a single question. Results One hundred sixty-five patients were enrolled (M/F 12/153; mean age 40.4±11.8 years, mean disease duration 109.1±96.2 months). No patients refused to answer, suggesting the acceptability of PASS. A total of 80% of patients rated their state as acceptable. The patients with an acceptable status had significantly lower mean SLEDAI-2K and ECLAM scores than the others [1.8±2.7 versus 3.4±2.3(P=0.004); 0.7±0.9 versus 1.4±1.1(P=0.0027)]. No significant differences were observed when considering chronic damage, evaluated with SLICC. Conclusions In the clinical practice, SLE patients assessment performed by using complex disease activity indices such as SLEDAI-2K and ECLAM, could be time consuming. In our study, for the first time, we used PASS, a quick and easily comprehensible tool, to evaluate the patients’ status, this single question seems to be able to discriminate patients with different disease activity, especially when this is determined by musculoskeletal involvement. PMID:24039971

  17. Immunogenicity and Safety of Influenza Vaccination in Systemic Lupus Erythematosus Patients Compared with Healthy Controls: A Meta-Analysis

    PubMed Central

    Liao, Zhengfa; Tang, Hao; Xu, Xiaojia; Liang, Yaping; Xiong, Yongzhen; Ni, Jindong

    2016-01-01

    Objective To assess the immunogenicity and safety of influenza vaccine in patients with systemic lupus erythematosus (SLE). Methods Relevant articles were retrieved from electronic databases. Seroprotection rate, seroconversion rate and factors that increase antibody geometric mean titer (GMT) were used as indices to measure the immunogenicity. The safety of vaccine was assessed through monitoring adverse events, which included side effects and SLE exacerbations. We performed a meta-analysis of influenza vaccine seroprotection, seroconversion and adverse effects. SLE exacerbation after vaccination was comprehensively described. We used the Committee for Proprietary Medicinal Products (CPMP) guidelines to determine whether influenza can induce adequate immunogenicity in patients with SLE. Results Eighteen studies with 1966 subjects met the inclusion criteria. At least 565 of the subjects were patients with low-to-moderate SLE Disease Activity Index (SLEDAI) score or stable SLE disease. Compared with the general population, seroprotection rate in SLE patients was significantly decreased in patients with H1N1 [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.27–0.50] and H3N2 vaccination (OR = 0.48, 95% CI: 0.24–0.93), but not influenza B vaccination (OR = 0.55, 95% CI: 0.24–1.25). Seroconversion rate also significantly decreased in patients with H1N1 (OR = 0.39, 95% CI: 0.27–0.57) and influenza B (OR = 0.47, 95% CI: 0.29–0.76) vaccination, but not H3N2 vaccination (OR = 0.62, 95% CI: 0.21–1.79). However, the immunogenicity of influenza vaccine in SLE patients almost reached that of the CPMP guidelines. The OR for side effects (patients versus healthy controls) was 3.24 (95% CI: 0.62–16.76). Among 1966 patients with SLE, 32 experienced mild exacerbation of SLE and five had serious side effects for other reasons. Conclusion Influenza vaccine has moderate effect on protecting patients with SLE. The side effects of influenza vaccine are not serious

  18. AGS, SLE, and RNASEH2 mutations: translating insights into therapeutic advances

    PubMed Central

    Pendergraft, William F.; Means, Terry K.

    2014-01-01

    Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by the presence of nucleic acid– and protein-targeting autoantibodies and an aberrant type I IFN expression signature. Aicardi-Goutières syndrome (AGS) is an autosomal-recessive encephalopathy in children that is characterized by mutations in numerous nucleic acid repair enzymes and elevated IFN levels. Phenotypically, patients with AGS and SLE share many similarities. Ribonuclease H2 (RNase H2) is a nucleic acid repair enzyme that removes unwanted ribonucleotides from DNA. In this issue of the JCI, Günther and colleagues provide an in-depth investigation of the mechanisms underlying the link between defective removal of ribonucleotides in AGS and SLE, and these findings will likely serve as a strong springboard to provide novel therapeutic inroads. PMID:25500879

  19. Psychotic Symptoms in a Child with Long Standing SLE Nephritis: Neuropsychiatric Manifestation or Sequelae to Lupus?

    PubMed Central

    Mahapatra, Ananya; Sharma, Pawan; Sagar, Rajesh

    2016-01-01

    Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease of unknown etiology, which affects multiple organ systems including the central nervous system (CNS). Though not common, childhood onset SLE is a known and established entity. Neuropsychiatric symptoms are common in childhood onset SLE. Of these, psychosis and behavioural symptoms are relatively rare, and there is no consensus on the proper treatment of such cases. We report a case of 13-year-old boy, diagnosed with lupus nephritis, and presented with psychosis and behavioural symptoms. The highlight of this case is that the psychiatric symptoms were present despite the primary illness being quiescent. Thus, the patient was treated with Olanzapine and lorazepam, while continuing immunosuppressive therapy as previously. Also, MRI brain revealed vasculitic changes in the right hemisphere, which might be one of the etiological factors playing role in the development of these neuropsychiatric symptoms. PMID:27274749

  20. Evaluation of Endothelial Cell Adhesion Molecules and Anti-C1q Antibody in Discriminating between Active and Non-Active Systemic Lupus Erythematosus

    PubMed Central

    Mahayidin, Hasni; Yahya, Nurul Khaiza; Wan Ghazali, Wan Syamimee; Mohd Ismail, Asmahan; Wan Ab Hamid, Wan Zuraida

    2016-01-01

    Background Detecting the active state of systemic lupus erythematosus (SLE) is important but challenging. This study aimed to determine the diagnostic accuracy of serum endothelial cell adhesion molecules (ICAM-1 and VCAM-1) and anti-C1q antibody in discriminating between active and non-active SLE. Methods Using SELENA-SLE disease activity index (SLEDAI), 95 SLE patients (45 active and 50 non-active) were assessed. A score above five was considered indicative of active SLE. The blood samples were tested for serum ICAM-1, VCAM-1 and anti-C1q antibody using enzyme-linked immunosorbent assay (ELISA). Results The levels of serum VCAM-1 and anti-C1q antibody were significantly higher in active SLE patients. Both VCAM-1 and anti-C1q were able to discriminate between active and non-active SLE (p-value < 0.001 and 0.005, respectively). From the receiver operating characteristic curves (ROCs) constructed, the optimal cut-off values for VCAM-1 and anti-C1q antibody in discriminating between active and non-active SLE were 30.5 ng/mL (69.0% sensitivity, 60.0% specificity, PPV 58.5%, NPV 66.7%) and 7.86 U/mL (75.6% sensitivity, 80% specificity, PPV 77.3%, NPV 78.4%), respectively. However, serum ICAM-1 level was unable to discriminate between the two groups (p-value = 0.193). Conclusion Anti-C1q antibody demonstrated the best diagnostic accuracy in discriminating between active and non-active SLE patients. PMID:27418866

  1. Sex Differences in monocytes and TLR4 associated immune responses; implications for systemic lupus erythematosus (SLE)

    PubMed Central

    Jiang, Wei; Gilkeson, Gary

    2014-01-01

    It has been shown that TLR7 and TLR9 signaling play a role in SLE pathogenesis. Our recent study revealed that estrogen receptor α knockout mice have impaired inflammatory responses to TLR3, TLR4, TLR7 and TLR9 ligand stimulation in DCs, B cells and whole spleen cells. These findings indicate that estrogen receptor mediated signaling may impact universal TLR responsiveness. Whether estrogen has a direct or indirect effect on TLR responsiveness by immune cells is not clear. There is evidence of a role of TLR4 in SLE disease pathogenesis, such as the kidney damage, the induction of CD40 and autoantibodies, the suppression of regulatory T cells, and the role of pro-inflammatory cytokines (e.g., IL-6, IL-1β, TNF-α) in SLE pathogenesis that can be induced by TLR4-mediated monocyte activation, suggesting that TLR4 and TLR4 responsiveness are also important for SLE disease. This review will focus on TLR4 responses and monocytes, which are understudied in systemic autoimmune diseases such as SLE. PMID:25309746

  2. Defect in regulation of Ca2+ movement in platelets from patients with systemic lupus erythematosus.

    PubMed

    Cheng, He-Hsiung; Ho, Chin-Man; Huang, Chun-Jen; Hsu, Shu-Shong; Jiann, Bang-Ping; Chen, Jin-Shyr; Huang, Jong-Khing; Chang, Hong-Tai; Lo, Yuk-Keung; Yeh, Jeng-Hsien; Jan, Chung-Ren

    2005-03-01

    The differences in the intracellular Ca(2+) responses to hormones in platelets from systemic lupus erythematosus (SLE) patients compared to normal humans have not been explored. This study examined the Ca(2+) signaling and density of platelets in normal, inactive and active SLE patients. The platelet number per mul in inactive and normal groups did not differ, whereas the number in active SLE patients was smaller than the other two groups by 60%. The intracellular free Ca(2+) levels ([Ca(2+)](i)) in response to stimulation of four endogenous Ca(2+) mobilizing hormones, 100 microM arachidonic acid (AA), 10 microM ADP, 10 nM platelet activation factor (PAF) and 1 microM thrombin, were investigated using the Ca(2+)-sensitive fluorescent dye, fura-2. The AA-induced [Ca(2+)](i) rises in normal and inactive groups were similar. In contrast, the AA-induced [Ca(2+)](i) rises in the active SLE group were significantly smaller than in the normal and inactive groups. The defect in the AA-induced [Ca(2+)](i) rises in active SLE groups appears to be caused by defective Ca(2+) influx and Ca(2+) releasing pathways because the AA-induced responses were not altered by removal of extracellular Ca(2+), whereas the AA-induced responses in normal and inactive SLE groups were reduced by removal of extracellular Ca(2+), and the AA-induced Ca(2+) release was smaller in the active SLE group. PAF, ADP and thrombin all induced [Ca(2+)](i) rises in the three groups, but no significant differences were found among the three groups. Together, the results indicate that cell density and Ca(2+) signaling in platelets from active SLE patients are altered in response to particular stimulators. In these regards, platelets from inactive SLE patients appear to be similar to those from normal humans. PMID:15591819

  3. Safety and efficacy of hCDR1 (Edratide) in patients with active systemic lupus erythematosus: results of phase II study

    PubMed Central

    Urowitz, Murray B; Isenberg, David A; Wallace, Daniel J

    2015-01-01

    Objective To evaluate the safety and efficacy of hCDR1 (Edratide) in patients with systemic lupus erythematosus (SLE). Methods Patients (n=340) with SLE ≥4 ACR criteria (4–11, mean 7) with active disease (SLEDAI-2K of 6–12). Patients were on average 7.1 years post-diagnosis and their organ involvement was mainly musculoskeletal, mucocutaneous and haematologic. Placebo or Edratide was administered subcutaneously weekly at doses of 0.5, 1.0 or 2.5 mg. The co-primary endpoints were SLEDAI-2K SLE Disease Activity and Adjusted Mean SLEDAI (AMS) reduction in patients compared with controls using a landmark analysis. Secondary outcomes were improvement in British Isles Lupus Assessment Group (BILAG) Responder Index and medicinal flare analysis. Results Edratide was safe and well tolerated. The primary endpoints based solely on SLEDAI-2K and AMS were not met. The secondary predefined endpoint, BILAG, was met for the 0.5 mg Edratide arm in the intention to treat (ITT) cohort (N=316) (OR=2.09, p=0.03) with trends in the 1.0 and 2.5 mg doses. There was also a positive trend in the Composite SLE Responder Index of the ITT cohort. Post hoc analysis showed that the BILAG secondary endpoint was also met for the 0.5 mg Edratide for a number of subgroup dose levels, including low or no steroids, seropositivity and patients with 2 grade BILAG improvement. Conclusions The favourable safety profile and encouraging clinically significant effects noted in some of the endpoints support the need for additional longer term Edratide studies that incorporate recent advances in the understanding and treatment of SLE, including steroid treatment algorithms, and using a composite primary endpoint which is likely to include BILAG. Trial registration number NCT00203151. PMID:26301100

  4. TH1/TH2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients

    PubMed Central

    MUÑOZ-VALLE, J F; VÁZQUEZ-DEL MERCADO, M; GARCÍA-IGLESIAS, T; OROZCO-BAROCIO, G; BERNARD-MEDINA, G; MARTÍNEZ-BONILLA, G; BASTIDAS-RAMÍREZ, B E; NAVARRO, A D; BUENO, M; MARTÍNEZ-LÓPEZ, E; BEST-AGUILERA, C R; KAMACHI, M; ARMENDÁRIZ-BORUNDA, J

    2003-01-01

    During the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-γ was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease. PMID:12562402

  5. The substantial burden of systemic lupus erythematosus on the productivity and careers of patients: a European patient-driven online survey

    PubMed Central

    Isenberg, David; Lerstrøm, Kirsten; Norton, Yvonne; Nikaï, Enkeleida; Pushparajah, Daphnee S.; Schneider, Matthias

    2013-01-01

    Objective. The objective of this study was to explore the burden of SLE and its effect on patients’ lives. Methods. The Lupus European Online (LEO) survey included patient-designed questions on demographics, SLE diagnosis, and the impact of SLE on careers. Three SLE-specific patient-reported outcome (PRO) questionnaires were also completed: the Lupus Quality of Life (LupusQoL), the Fatigue Severity Scale (FSS), and the Work Productivity and Activity Impairment (WPAI)-Lupus v2.0. The survey was available online in five languages from May through August 2010. All self-identified SLE participants were eligible to respond. Survey results were analysed using descriptive statistics. Multivariate linear regression explored factors contributing to impaired productivity. Results. Of the 2070 European SLE patients completing the survey, 93.1% were women, 86.7% were aged <50 years and 71.8% had a college or university education. More than two-thirds of respondents (69.5%) reported that SLE affected their careers; 27.7% changed careers within a year of diagnosis. All LupusQoL domains (score range 0–100) were impaired, with fatigue (median domain score 43.8) being the most affected and intimate relationships (median domain score 75.0) the least. Most patients (82.5%) reported fatigue (FSS score ≥4). Productivity was impaired across all WPAI domains, both at work and in general activities. Fatigue, an inability to plan and reduced physical health were significantly associated with impaired productivity. Patients whose careers were affected by SLE had worse health-related quality of life, more fatigue and worse productivity than patients whose careers were not affected. Conclusion. LEO survey respondents reported that SLE negatively affects their daily lives, productivity and career choices. PMID:24049101

  6. Antiphospholipid Antibodies are Associated with Low Levels of Complement C3 and C4 in Patients with Systemic Lupus Erythematosus.

    PubMed

    Garabet, L; Gilboe, I-M; Mowinckel, M-C; Jacobsen, A F; Mollnes, T E; Sandset, P M; Jacobsen, E-M

    2016-08-01

    Complement activation and low complement levels are common in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are found in about 30-40% of patients with SLE. This study aimed to investigate the association between aPL and complement levels in patients with SLE. Serum samples were collected from 269 patients with SLE enrolled in the Norwegian Systemic Connective Tissue and Vasculitis Registry (NOSVAR) during 2003-2009, and from 353 controls. All samples were analysed for anti-β2 glycoprotein 1 (anti-β2GP1) and anticardiolipin antibodies (aCL), C-reactive protein (CRP) and complement components C3 and C4. Median CRP level was significantly higher in cases than in controls (2.06 versus 0.90 mg/l; P < 0.0001). No significant difference in CRP was found between SLE patients with or without aPL (2.09 versus 1.89; P = 0.665). Median C3 levels were similar in cases (1.03 g/l) and controls (1.00 g/l), whereas median C4 levels were 0.16 g/l in cases versus. 0.19 in controls (P < 0.0001). However, aPL-positive SLE patients had significantly lower median C3 levels (0.92 versus. 1.07 g/l; P = 0.001) and C4 levels (0.11 versus 0.16 g/l; P < 0.0001) compared to aPL-negative patients. Lower C3 and C4 values in aPL-positive SLE patients may reflect a higher consumption of C3 and C4 due to more pronounced complement activation in aPL-positive SLE patients compared to SLE patients without aPL. PMID:27135178

  7. Vitamin D Levels Are Associated with Expression of SLE, but Not Flare Frequency.

    PubMed

    Squance, Marline L; Reeves, Glenn E M; Tran, Huy A

    2014-01-01

    This study explores links between vitamin D deficiency (25(OH)D = 50 nmol/L) and serological autoimmunity (ANA > 1 : 80) and frequency of self-reported flares (SRF) in participants with clinical autoimmunity (SLE). 25(OH)D levels of 121 females were quantified and compared. The cohort consisted of 80 ACR defined SLE patients and 41 age and sex matched controls. Association analysis of log2 (25(OH)D) levels and ANA 80 positivity was undertaken via two-sample t-tests and regression models. Significant differences were found for 25(OH)D levels (mean: control 74 nmol/L (29.5 ng/ml); SLE 58 nmol/L (23.1 ng/ml), P = 0.04), 25(OH)D deficiency (P = 0.02). Regression models indicate that, for a twofold rise in 25(OH)D level, the odds ratio (OR) for ANA-positivity drops to 36% of the baseline OR. No link was found between SRF-days and 25(OH)D levels. Our results support links between vitamin D deficiency and expression of serological autoimmunity and clinical autoimmunity (SLE). However, no demonstrable association between 25(OH)D and SRF was confirmed, suggesting independent influences of other flare-inducing factors. Results indicate that SLE patients have high risk of 25(OH)D deficiency and therefore supplementation with regular monitoring should be considered as part of patient management. PMID:25506363

  8. Vitamin D Levels Are Associated with Expression of SLE, but Not Flare Frequency

    PubMed Central

    Squance, Marline L.; Reeves, Glenn E. M.; Tran, Huy A.

    2014-01-01

    This study explores links between vitamin D deficiency (25(OH)D = 50 nmol/L) and serological autoimmunity (ANA > 1 : 80) and frequency of self-reported flares (SRF) in participants with clinical autoimmunity (SLE). 25(OH)D levels of 121 females were quantified and compared. The cohort consisted of 80 ACR defined SLE patients and 41 age and sex matched controls. Association analysis of log2 (25(OH)D) levels and ANA 80 positivity was undertaken via two-sample t-tests and regression models. Significant differences were found for 25(OH)D levels (mean: control 74 nmol/L (29.5 ng/ml); SLE 58 nmol/L (23.1 ng/ml), P = 0.04), 25(OH)D deficiency (P = 0.02). Regression models indicate that, for a twofold rise in 25(OH)D level, the odds ratio (OR) for ANA-positivity drops to 36% of the baseline OR. No link was found between SRF-days and 25(OH)D levels. Our results support links between vitamin D deficiency and expression of serological autoimmunity and clinical autoimmunity (SLE). However, no demonstrable association between 25(OH)D and SRF was confirmed, suggesting independent influences of other flare-inducing factors. Results indicate that SLE patients have high risk of 25(OH)D deficiency and therefore supplementation with regular monitoring should be considered as part of patient management. PMID:25506363

  9. Novel functional activities of anti-DNA autoantibodies from sera of patients with lymphoproliferative and autoimmune diseases.

    PubMed

    Kozyr, A V; Kolesnikov, A V; Aleksandrova, E S; Sashchenko, L P; Gnuchev, N V; Favorov, P V; Kotelnikov, M A; Iakhnina, E I; Astsaturov, I A; Prokaeva, T B; Alekberova, Z S; Suchkov, S V; Gabibov, A G

    1998-10-01

    DNA-hydrolyzing activity of IgG autoantibodies from sera of patients with various types of lymphoproliferative diseases was investigated. The association of DNA-hydrolyzing activity with the antibody (Ab) fraction has been proved by newly developed affinity-capture assay. Study of abzyme incidence in blood tumors and systemic lupus erythematosis (SLE) revealed linkage of anti-DNA Ab catalysts to mature B-cell tumors, and increased probability of DNA-abzymes formation on the background of autoimmune manifestations. These data suggest possible similarity between mechanisms of abzyme formation in SLE and B-cell lymphomas. A new mechanism of formation of DNA-specific catalytic Abs has been proposed based on the increased crossreactivity of polyclonal DNA-abzymes to DNA-depleted nuclear matrix proteins. The possibility of the abzyme production as Ab to the energetically destabilized ground state of the antigen has been discussed. Preliminary results were obtained that indicate the complement-independent cytotoxicity of anti-DNA autoantibodies isolated from blood of patients with SLE and chronic lymphocytic leukemia. PMID:10214696

  10. Seasonal distribution of systemic lupus erythematosus activity and its correlation with climate factors.

    PubMed

    Yang, Jie; Lu, Yu-Wei; Pan, Hai-Feng; Tao, Jin-Hui; Zou, Yan-Feng; Bao, Wei; Ye, Dong-Qing

    2012-08-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a variety of clinical manifestations. Although inter-individual variations exist with respect to susceptibility to develop SLE, no study has been carried out to determine the role of different climate conditions in predisposing the susceptible individuals to SLE. The objective of this study was to investigate the role of different seasons and climate factors on SLE activity. From 2000 to 2009, the seasonal distribution of 2,802 active SLE patients recruited from Anhui Provincial Hospital and the First Affiliated Hospital of Anhui Medical University was analyzed retrospectively. The climate data were provided by the Institute of Geographical Sciences and Resources, Chinese Academy of Sciences. The correlation between climate factors and SLE activity was also analyzed. The proportion of active SLE patients in winter, spring, summer, and autumn was 10.06, 10.31, 9.74, and 8.66‰, respectively. In autumn, the proportion was much lower than that in winter and spring (P < 0.05). The proportion among winter, spring, and summer had no statistical difference (P > 0.05). The number of active SLE patients had no correlation with air temperature (r = 0.483, P > 0.05), relative humidity (r = -0.294, P > 0.05), and sunshine percentage (r = 0.503, P > 0.05), but it had positive correlation with amount of precipitation (r = 0.601, P < 0.05), wind velocity (r = 0.713, P < 0.01), and sunshine duration (r = 0.769, P < 0.01) and negative correlation with barometric pressure (r = -0.664, P < 0.05). The disease activity of patients with SLE is affected by seasons and climate factors. PMID:21667078

  11. CD38, CD81 and BAFFR combined expression by transitional B cells distinguishes active from inactive systemic lupus erythematosus.

    PubMed

    Henriques, Ana; Silva, Isabel; Inês, Luís; Souto-Carneiro, M Margarida; Pais, M Luísa; Trindade, Hélder; da Silva, José António Pereira; Paiva, Artur

    2016-05-01

    In view of its heterogeneous presentation and unpredictable course, clinical management of systemic lupus erythematosus (SLE) is difficult. There is a need for biomarkers and diagnostic aids to monitor SLE disease activity and severity prior to, during and after treatment. We undertook this study to search for unique phenotypic patterns in each peripheral blood (PB) B cell subset, capable of distinguishing SLE patients with inactive disease versus SLE patients with active disease versus controls by using an automated population separator (APS) visualization strategy. PB was collected from 41 SLE patients and 28 age- and gender-matched controls. We analyzed the cell surface markers (in a tube CD20/CD27/CD19/CD45/CD38/CD81/BAFFR combination) expression on PB B cell subsets using principal component analysis, implemented in the APS software tool. Overall, our analysis indicates that active SLE can be distinguished from inactive SLE on the basis of a single tube analysis, focused on the decreased expression of CD38, CD81 and BAFFR in transitional B cells. The cluster analysis of immunophenotypic profiles of B cell subsets highlighted disease-specific abnormalities on transitional B cells that emerge as promising surrogate markers for disease activity. Further validation is needed with larger samples and prospective follow-up of patients. PMID:25894569

  12. Bilateral macular infarction as an ocular manifestation of systemic lupus erythematosus (SLE)

    PubMed Central

    Hu, Chih-Ling; Peng, Kai-Ling

    2014-01-01

    We report a rare case of bilateral macular infarction as an ocular presenting sign of systemic lupus erythematosus (SLE). A 29-year-old woman presented to our ophthalmologic clinic with a 1-week history of progressive visual loss in her left eye after she had visited a rheumatologic clinic where SLE was diagnosed. At examination, best-corrected visual acuity (BCVA) of the right eye was 6/6, and for the left was counting fingers. Fundus examination revealed perivascular hard exudates along some branches of vessels in both eyes. After pulse therapy, her BCVA in the right eye declined to 6/30 and in the left improved to 3/60. She was administered sub-Tenon’s injections of triamcinolone acetonide 50 mg/week in both eyes for 3 weeks. Her BCVA improved to 3/6 in her right eye and remained at 3/60 in her left eye. Macular infarction is an uncommon but most severe complication of SLE. Early and regular exam of the fundus in patients with SLE is necessary to avoid progression of severe ocular complications. PMID:25246764

  13. A case of SLE with acute, subacute and chronic cutaneous lesions successfully treated with Dapsone.

    PubMed

    Neri, R; Mosca, M; Bernacchi, E; Bombardieri, S

    1999-01-01

    We describe a patient with systemic lupus erythematosus (SLE) who exhibited severe cutaneous involvement characterized by the simultaneous presence of acute, subacute and discoid lesions in association with anti-S1 antibodies. After she failed to respond to chloroquine, medium to low dose steroids, steroid pulses, retinoids and cyclophosphamide, the patient was treated with Dapsone and a dramatic improvement in the cutaneous lesions was seen after only one month. PMID:10342718

  14. Increased expression of low density granulocytes in juvenile-onset systemic lupus erythematosus patients correlates with disease activity.

    PubMed

    Midgley, A; Beresford, M W

    2016-04-01

    Neutrophils are implicated in a wide range of non-infectious inflammatory conditions. A subset of neutrophils in the peripheral circulation of systemic lupus erythematosus (SLE) patients has been described and termed low density granulocytes (LDGs). This study investigates the expression of LDG in juvenile-onset SLE (JSLE) patients compared to controls, and any correlations with disease activity.Neutrophils and LDGs were isolated from JSLE (n = 13) and paediatric non-inflammatory control patients (n = 12). Cell populations were assessed and compared using flow cytometry and morphological analysis. Standard clinical data, which included disease activity markers/scores, were collected for each patient.Significantly increased LDG expression (%mean ± SEM, range) was observed in JSLE patients (10.4 ± 3.26, 3.41-36.3) compared to controls (2.4 ± 0.44, 0.36-5.27; p = 0.005). A statistically significant positive correlation was observed between LDG expression and the British Isles Lupus Activity Group (correlation coefficient 0.685; p = 0.010) and SLE Disease Activity Index (correlation coefficient 0.567; p = 0.043) and the biomarker of dsDNA-antibodies (correlation coefficient 0.590; p = 0.043).Here we observe increased expression in LDGs in JSLE patients, which correlate with dsDNA antibody concentration and scores of disease activity. These correlations indicate that the increased LDG expression observed in this study may have a potential role in the pathogenesis of JSLE, and may be a useful biomarker. PMID:26453665

  15. Prevalence of 13 autoantibodies and of the 16/6 and related pathogenic idiotypes in 465 patients with systemic lupus erythematosus and their relationship with disease activity.

    PubMed

    Villarreal, G M; Drenkard, C; Villa, A R; Slor, H; Shafrir, S; Bakimer, R; Shoenfeld, Y; Alarcón-Segovia, D

    1997-01-01

    With a cross sectional study of 465 consecutive systemic lupus erythematosus (SLE) patients tested for 13 autoantibodies (Aab) and two idiotypes we determined the prevalence of Aab according to disease activity, both general and at particular organ systems. Seventy seven percent of SLE sera had at least one Aab and 56% had it at high titres. Pathogenic idiotypes had a prevalence of less than 10% and 166 sera had Aab to 5 or more antigens and 9 sera had Aab against all 13 antigens tested. Patients with active disease had increased prevalence of Aab to DNP, ssDNA, ENA, mitochondria and histones when considered at 5 s.d. above the mean of normal controls. The higher positivity of Aab in patients with active disease was confirmed in logistic regression analysis adjusted by age, disease duration, and intensity of treatment. A trend was observed of increased prevalence and titres of Aab from inactive disease without treatment, to inactive disease but still being treated, to active disease. Only 22% of patients with active disease had no Aab and the higher the number of Aab the higher the frequency of active disease. Patients with active arthritis, and to a lesser degree those with active mucocutaneous involvement, had higher prevalence and titres of most autoantibodies than patients with disease activity at other organ systems. Active renal disease associated only with anti-dsDNA, whereas active CNS disease associated with anti-mitochondrial Aab. Our findings support the vision of SLE as an immune dysregulation leading to polyclonal B cell activation with resulting production of multiple Aab. Their profiles seem influenced by genetical, hormonal and environmental factors and, in turn, they contribute to the clinical picture in each patient. Disease activity influences the presence of some, but not all, Aab and some of them may remain present in some patients, even in remission. PMID:9229360

  16. Risk and predictors of work disability in Chinese patients with systemic lupus erythematosus.

    PubMed

    Mok, C C; Cheung, M Y; Ho, L Y; Yu, K L; To, C H

    2008-12-01

    The aim of this study is to determine the risk and predictive factors for work disability in patients with SLE. A cross-sectional questionnaire study was performed to evaluate the employment status of a sample of consecutive Chinese patients with SLE. Demographic, socioeconomic data (age, gender, marital status, years of education and household income), employment status, self-reported fatigue score and disease characteristics (SLE duration, organ damage and disease activity) were collected. Work disability was defined by the failure to work due to SLE. The cumulative incidence of work disability since the time of SLE diagnosis was studied by a Kaplan Meier's plot, and factors predictive of work disability were studied by Cox regression. A total of 147 patients with SLE were studied (mean age = 39.4 +/- 11.3 years; 95% women). Among 105 patients who were working at the time of SLE diagnosis, 39 (37%) lost their ability to work as a result of SLE after a mean disease duration of 10.0 +/- 6.1 years. Twenty-two (56%) patients lost their work ability within 2 years of diagnosis of SLE. The self-reported reasons for job loss were musculoskeletal pain (87%), skin disease (26%), renal problem (21%), fatigue (85%), memory deterioration (51%), anxiety or depressive symptoms (74%), too frequent sick leave (10%) and long-term hospitalisation (10%). The cumulative risk of work disability was 36% at 5 years after SLE diagnosis. In a Cox regression model, age (HR = 1.06 [1.02-1.11] per year; P = 0.008), self-reported fatigue score (HR = 1.06 [1.01-1.10] per point; P = 0.01) and mean disease activity score in the preceding two years (HR = 1.20 [1.02-1.42] per point; P = 0.03) were independently associated with working disability. In all, 37% of this group of patients with SLE lost their work ability after having the disease for 10 years. More than 50% of these patients developed work disability within the first 2 years of SLE diagnosis. Older age, fatigue and more active disease

  17. Disease Activity, Proteinuria, and Vitamin D Status in Children with Systemic Lupus Erythematosus and Juvenile Dermatomyositis

    PubMed Central

    Robinson, Angela Byun; Thierry-Palmer, Myrtle; Gibson, Keisha L.; Rabinovich, C. Egla

    2011-01-01

    Objective To evaluate relationships between vitamin D, proteinuria, and disease activity in pediatric systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM). Study design Multiple linear regression was used to associate subject-reported race, sunscreen use, and vitamin D intake with physician-assessed disease activity and serum 25-hydroxyvitamin D [25(OH)D] in subjects with pediatric SLE (n = 37) or JDM (n = 21). Serum 25(OH)D was correlated with urinary vitamin D binding protein/creatinine ratio (DBP/C) and other indicators of proteinuria. Results Serum 25(OH)D levels in subjects with SLE were inversely associated with the natural log of urinary DBP/C (r = −0.63, p < 0.001) and urine protein to creatinine ratio (r = −0.60, p<0.001), with an adjusted mean 10.9 (95% CI 5.1, 16.8) ng/mL decrease in 25(OH)D for those with proteinuria. Excluding subjects with proteinuria, serum 25(OH)D levels were inversely associated with disease activity in JDM, but not in SLE. Overall, 66% of all subjects were taking concurrent corticosteroids, but this was not associated with 25(OH)D levels. Conclusions Low serum 25(OH)D in patients with SLE is associated with proteinuria and urinary DBP. Vitamin D deficiency is associated with disease activity in patients with JDM and SLE; this relationship in SLE may be confounded by proteinuria. PMID:21924736

  18. Current and Novel Therapeutics in Treatment of SLE

    PubMed Central

    Yildirim-Toruner, Cagri; Diamond, Betty

    2011-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with significant clinical heterogeneity. Recent advances in our understanding of the genetic, molecular and cellular basis of autoimmune diseases and especially SLE have led to the application of novel and targeted treatments. While many treatment modalities are effective in lupus-prone mice, the situation is more complex in humans. This article reviews the general approach to the therapy of SLE, focusing on current approved therapies and novel approaches that might be used in the future. PMID:21281862

  19. Heightened cleavage of Axl receptor tyrosine kinase by ADAM metalloproteases may contribute to disease pathogenesis in SLE.

    PubMed

    Orme, Jacob J; Du, Yong; Vanarsa, Kamala; Mayeux, Jessica; Li, Li; Mutwally, Azza; Arriens, Cristina; Min, Soyoun; Hutcheson, Jack; Davis, Laurie S; Chong, Benjamin F; Satterthwaite, Anne B; Wu, Tianfu; Mohan, Chandra

    2016-08-01

    Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice. We hypothesized that sAxl in SLE serum originates from the surface of leukocytes and that the loss of leukocyte Axl contributes to the disease. We determined that macrophages and B cells are a source of sAxl in SLE and in lupus-prone mice. Shedding of the Axl ectodomain from the leukocytes of lupus-prone mice is mediated by the matrix metalloproteases ADAM10 and TACE (ADAM17). Loss of Axl from lupus-prone macrophages renders them unresponsive to Gas6-induced anti-inflammatory signaling in vitro. This phenotype is rescued by combined ADAM10/TACE inhibition. Mice with Axl-deficient macrophages develop worse disease than controls when challenged with anti-glomerular basement membrane (anti-GBM) sera in an induced model of nephritis. ADAM10 and TACE also mediate human SLE PBMC Axl cleavage. Collectively, these studies indicate that increased metalloprotease-mediated cleavage of leukocyte Axl may contribute to end organ disease in lupus. They further suggest dual ADAM10/TACE inhibition as a potential therapeutic modality in SLE. PMID:27237127

  20. The Percentage of FoxP3+Helios+ Treg Cells Correlates Positively With Disease Activity in Systemic Lupus Erythematosus

    PubMed Central

    Golding, Amit; Hasni, Sarfaraz; Illei, Gabor; Shevach, Ethan M.

    2013-01-01

    Objective To assess the use of Helios in combination with FoxP3 as a superior method for identifying non–cytokine-producing human Treg cells in patients with systemic lupus erythematosus (SLE) and to determine if FoxP3+Helios+ Treg cells are maintained at normal levels in patients with clinically active disease. Methods Peripheral blood mononuclear cells (PBMCs) were purified from the blood of healthy volunteer donors and from 52 consecutive patients with SLE of varying clinical activity (Systemic Lupus Erythematosus Disease Activity Index scores of 0, 2–4, and ≥5). PBMCs (either fresh or after 4 hours of stimulation for cytokine production) were then analyzed by flow cytometry for the expression of cell surface markers (CD4, CD25, CD127, and CD45RA) and transcription factors (FoxP3 and Helios), as well as for the production of cytokines (interleukin-2 and interferon- γ). Results FoxP3+Helios+ Treg cells were found to be non–cytokine producing in both SLE patients and healthy controls. Patients with clinically active SLE had higher percentages of FoxP3+Helios+ Treg cells than did patients with inactive SLE or healthy controls. When corrected for the total CD4 cell count, the absolute numbers of FoxP3+Helios+ Treg cells in patients with moderately-to-highly active SLE were normal. Conclusion Previous reports of a deficiency in Treg cell number or function in SLE are limited by their use of CD25, either alone or in combination with other markers, to identify human Treg cells. Helios in combination with FoxP3 is a superior method for detecting all non–cytokine-producing Treg cells, irrespective of CD25 or CD45RA expression. Using this method, we showed that FoxP3+Helios+ Treg cell numbers are not reduced in patients with clinically active SLE. PMID:23925905

  1. Allelic heterogeneity in NCF2 associated with systemic lupus erythematosus (SLE) susceptibility across four ethnic populations

    PubMed Central

    Kim-Howard, Xana; Sun, Celi; Molineros, Julio E.; Maiti, Amit K.; Chandru, Hema; Adler, Adam; Wiley, Graham B.; Kaufman, Kenneth M.; Kottyan, Leah; Guthridge, Joel M.; Rasmussen, Astrid; Kelly, Jennifer; Sánchez, Elena; Raj, Prithvi; Li, Quan-Zhen; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Lee, Shin-Seok; Han, Bok-Ghee; Olsen, Nancy J.; Karp, David R.; Moser, Kathy; Pons-Estel, Bernardo A.; Wakeland, Edward K.; James, Judith A.; Harley, John B.; Bae, Sang-Cheol; Gaffney, Patrick M.; Alarcón-Riquelme, Marta; Looger, Loren L.; Nath, Swapan K.; Acevedo, Eduardo; Acevedo, Eduardo; La Torre, Ignacio García-De; Maradiaga-Ceceña, Marco A.; Cardiel, Mario H.; Esquivel-Valerio, Jorge A.; Rodriguez-Amado, Jacqueline; Moctezuma, José Francisco; Miranda, Pedro; Perandones, Carlos; Aires, Buenos; Castel, Cecilia; Laborde, Hugo A.; Alba, Paula; Musuruana, Jorge; Goecke, Annelise; Foster, Carola; Orozco, Lorena; Baca, Vicente

    2014-01-01

    Recent reports have associated NCF2, encoding a core component of the multi-protein NADPH oxidase (NADPHO), with systemic lupus erythematosus (SLE) susceptibility in individuals of European ancestry. To identify ethnicity-specific and -robust variants within NCF2, we assessed 145 SNPs in and around the NCF2 gene in 5325 cases and 21 866 controls of European-American (EA), African-American (AA), Hispanic (HS) and Korean (KR) ancestry. Subsequent imputation, conditional, haplotype and bioinformatic analyses identified seven potentially functional SLE-predisposing variants. Association with non-synonymous rs17849502, previously reported in EA, was detected in EA, HS and AA (PEA = 1.01 × 10−54, PHS = 3.68 × 10−10, PAA = 0.03); synonymous rs17849501 was similarly significant. These SNPs were monomorphic in KR. Novel associations were detected with coding variants at rs35937854 in AA (PAA = 1.49 × 10−9), and rs13306575 in HS and KR (PHS = 7.04 × 10−7, PKR = 3.30 × 10−3). In KR, a 3-SNP haplotype was significantly associated (P = 4.20 × 10−7), implying that SLE predisposing variants were tagged. Significant SNP–SNP interaction (P = 0.02) was detected between rs13306575 and rs17849502 in HS, and a dramatically increased risk (OR = 6.55) with a risk allele at each locus. Molecular modeling predicts that these non-synonymous mutations could disrupt NADPHO complex assembly. The risk allele of rs17849501, located in a conserved transcriptional regulatory region, increased reporter gene activity, suggesting in vivo enhancer function. Our results not only establish allelic heterogeneity within NCF2 associated with SLE, but also emphasize the utility of multi-ethnic cohorts to identify predisposing variants explaining additional phenotypic variance (‘missing heritability’) of complex diseases like SLE. PMID:24163247

  2. Allelic heterogeneity in NCF2 associated with systemic lupus erythematosus (SLE) susceptibility across four ethnic populations.

    PubMed

    Kim-Howard, Xana; Sun, Celi; Molineros, Julio E; Maiti, Amit K; Chandru, Hema; Adler, Adam; Wiley, Graham B; Kaufman, Kenneth M; Kottyan, Leah; Guthridge, Joel M; Rasmussen, Astrid; Kelly, Jennifer; Sánchez, Elena; Raj, Prithvi; Li, Quan-Zhen; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Lee, Shin-Seok; Han, Bok-Ghee; Olsen, Nancy J; Karp, David R; Moser, Kathy; Pons-Estel, Bernardo A; Wakeland, Edward K; James, Judith A; Harley, John B; Bae, Sang-Cheol; Gaffney, Patrick M; Alarcón-Riquelme, Marta; Looger, Loren L; Nath, Swapan K

    2014-03-15

    Recent reports have associated NCF2, encoding a core component of the multi-protein NADPH oxidase (NADPHO), with systemic lupus erythematosus (SLE) susceptibility in individuals of European ancestry. To identify ethnicity-specific and -robust variants within NCF2, we assessed 145 SNPs in and around the NCF2 gene in 5325 cases and 21 866 controls of European-American (EA), African-American (AA), Hispanic (HS) and Korean (KR) ancestry. Subsequent imputation, conditional, haplotype and bioinformatic analyses identified seven potentially functional SLE-predisposing variants. Association with non-synonymous rs17849502, previously reported in EA, was detected in EA, HS and AA (P(EA) = 1.01 × 10(-54), PHS = 3.68 × 10(-10), P(AA) = 0.03); synonymous rs17849501 was similarly significant. These SNPs were monomorphic in KR. Novel associations were detected with coding variants at rs35937854 in AA (PAA = 1.49 × 10(-9)), and rs13306575 in HS and KR (P(HS) = 7.04 × 10(-7), P(KR) = 3.30 × 10(-3)). In KR, a 3-SNP haplotype was significantly associated (P = 4.20 × 10(-7)), implying that SLE predisposing variants were tagged. Significant SNP-SNP interaction (P = 0.02) was detected between rs13306575 and rs17849502 in HS, and a dramatically increased risk (OR = 6.55) with a risk allele at each locus. Molecular modeling predicts that these non-synonymous mutations could disrupt NADPHO complex assembly. The risk allele of rs17849501, located in a conserved transcriptional regulatory region, increased reporter gene activity, suggesting in vivo enhancer function. Our results not only establish allelic heterogeneity within NCF2 associated with SLE, but also emphasize the utility of multi-ethnic cohorts to identify predisposing variants explaining additional phenotypic variance ('missing heritability') of complex diseases like SLE. PMID:24163247

  3. T cell reactivity against the SmD183–119 C terminal peptide in patients with systemic lupus erythematosus

    PubMed Central

    Riemekasten, G; Weiss, C; Schneider, S; Thiel, A; Bruns, A; Schumann, F; Blass, S; Burmester, G; Hiepe, F

    2002-01-01

    Background: The SmD183–119 peptide is a major target of the B cell response in patients with systemic lupus erythematosus (SLE). Objective: To investigate the T cell response directed against this peptide, its disease specificity, and possible impact on SLE pathogenesis. Methods: Peripheral blood mononuclear cells derived from 28 patients with SLE and 29 healthy and disease controls were stimulated by the SmD183–119 and the recombinant (r)SmD1 protein, and [3H]thymidine incorporation was measured. Patients with SLE were simultaneously tested for autoantibodies, disease activity, clinical symptoms, and medical treatments. Results: T cell reactivity against the SmD183–119 peptide was detected in 11/28 (39%) patients with SLE and against the rSmD1 protein in 10/28 (36%) patients. In contrast, only 2/29 (7%) controls exhibited SmD1 reactivity. An analysis of proliferation kinetics showed that SmD1 reactive T cells are activated in vivo, as additionally confirmed by cytometric analysis. Addition of mammalian dsDNA to rSmD1 enhanced the rSmD1-specific T cell response. SmD183–119-specific T cell reactivity was significantly more common in patients with cardiac and pulmonary symptoms. No correlation between T and B cell responses and disease activity was seen. Conclusion: SmD183–119 is a major T cell epitope of SmD1, commonly recognised by T cells from patients with SLE and much less commonly found by healthy or disease controls. This strong T cell reactivity as well as the high frequency and specificity of anti-SmD183–119 antibodies in SLE suggest a possible role in SLE pathogenesis, at least in a subset of patients. PMID:12176801

  4. SLE: Another Autoimmune Disorder Influenced by Microbes and Diet?

    PubMed Central

    Mu, Qinghui; Zhang, Husen; Luo, Xin M.

    2015-01-01

    Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. Despite years of study, the etiology of SLE is still unclear. Both genetic and environmental factors have been implicated in the disease mechanisms. In the past decade, a growing body of evidence has indicated an important role of gut microbes in the development of autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. However, such knowledge on SLE is little, though we have already known that environmental factors can trigger the development of lupus. Several recent studies have suggested that alterations of the gut microbial composition may be correlated with SLE disease manifestations, while the exact roles of either symbiotic or pathogenic microbes in this disease remain to be explored. Elucidation of the roles of gut microbes – as well as the roles of diet that can modulate the composition of gut microbes – in SLE will shed light on how this autoimmune disorder develops, and provide opportunities for improved biomarkers of the disease and the potential to probe new therapies. In this review, we aim to compile the available evidence on the contributions of diet and gut microbes to SLE occurrence and pathogenesis. PMID:26648937

  5. Increased CD45RA+FoxP3low Regulatory T Cells with Impaired Suppressive Function in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Wang, Weiwei; Shan, Jianping; Lin, Fujun; Jiang, Gengru; Yang, Yuan H.; Wang, Die; Xu, Dakang; Shen, Lisong

    2012-01-01

    Background The role of naturally occurring regulatory T cells (Treg) in the control of the development of systemic lupus erythematosus (SLE) has not been well defined. Therefore, we dissect the phenotypically heterogeneous CD4+FoxP3+ T cells into subpopulations during the dynamic SLE development. Methodlogy/Principal Findings To evaluate the proliferative and suppressive capacities of different CD4+ T cell subgroups between active SLE patients and healthy donors, we employed CD45RA and CD25 as surface markers and carboxyfluorescein diacetatesuccinimidyl ester (CFSE) dilution assay. In addition, multiplex cytokines expression in active SLE patients was assessed using Luminex assay. Here, we showed a significant increase in the frequency of CD45RA+FoxP3low naive Treg cells (nTreg cells) and CD45RA−FoxP3low (non-Treg) cells in patients with active SLE. In active SLE patients, the increased proportions of CD45RA+FoxP3low nTreg cells were positively correlated with the disease based on SLE disease activity index (SLEDAI) and the status of serum anti-dsDNA antibodies. We found that the surface marker combination of CD25+CD45RA+ can be used to defined CD45RA+FoxP3low nTreg cells for functional assays, wherein nTreg cells from active SLE patients demonstrated defective suppression function. A significant correlation was observed between inflammatory cytokines, such as IL-6, IL-12 and TNFα, and the frequency of nTreg cells. Furthermore, the CD45RA+FoxP3low nTreg cell subset increased when cultured with SLE serum compared to healthy donor serum, suggesting that the elevated inflammatory cytokines of SLE serum may promote nTreg cell proliferation/expansion. Conclusions/Significance Our results indicate that impaired numbers of functional CD45RA+FoxP3low naive Treg cell and CD45RA−FoxP3low non-suppressive T cell subsets in inflammatory conditions may contribute to SLE development. Therefore, analysis of subsets of FoxP3+ T cells, using a combination of FoxP3, CD25 and CD

  6. Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades

    PubMed Central

    Moss, K; Ioannou, Y; Sultan, S; Haq, I; Isenberg, D

    2002-01-01

    Objective: To examine the mortality rate and causes of death in a cohort of 300 patients with systemic lupus erythematosus (SLE). Methods: A retrospective analysis was performed on all patients attending the SLE clinic between 1978 and 2000. Information was obtained on those patients lost to follow up. Cause of death was analysed and categorised as early (<5 years after diagnosis of SLE) and late (>5 years after diagnosis of SLE). Standardised mortality rates were obtained. Results: The patients were followed up for a median of 8.3 years. Seventy three (24%) patients were no longer followed up at the end of the study period, of whom 41 (14%) had died. Of the 32 patients lost to follow up, 14 were being actively followed up within the UK, 16 were followed up outside the UK, and two patients were untraceable. The most common cause of death was malignancy, which accounted for eight (20%) deaths, followed by infection and vascular disease, which accounted for seven (17%) deaths each. Conclusions: Malignancy was the most common cause of death. Cause of death varied depending on disease duration. Forty per cent of early deaths were due to SLE related renal disease, whereas 23% of late deaths were due to vascular causes. Death due to infection occurred throughout the follow up period. There was a fourfold increased risk of death in our cohort of patients with SLE compared with the general population. PMID:11959764

  7. Pattern of MRI brain in neuro-psychiatric SLE. Effect of anti-phospholipid antibodies: A study at a tertiary care teaching hospital

    PubMed Central

    Parvez, Khalid; Al-Arfaj, Abdul Rahman Saud; Hamdani, Muhammad Afzal; Naseeb, Faisal; Daif, Abdulkader; Hussain, Sajjad

    2015-01-01

    Objective: To compare the neuro-radiologic findings in Systemic lupus erythematosus (SLE) patients with and without antiphospholipid antibodies (aPL) in different neuro-psychiatric manifestations. Methods: This cross-sectional comparative study was carried out at King Khalid University Hospital, a tertiary care teaching hospital, Riyadh, Saudi Arabia from June 2012 to January 2015. Ninety seven SLE patients with neuro-psychiatric manifestations were included in the study and divided into two groups. Group I (50 patients) SLE with aPL and group II (47 patients) SLE without aPL. We compared Demographic features, clinical manifestations and magnetic resonance imaging (MRI) brain findings. Results: Demographic and clinical characteristics of two groups were similar. In Group-I, anticardiolipin antibodies (aCL) were most common (86%). In patients with headache, most of the patients in Group-I had white matter hyperintensities (WMHIs) (50% vs 27%) while most of the patients in Group-II had normal MRI brain (38% vs 73%). Similarly WMHIs were found more in Group-I patients with seizures (60% vs 21%), while ischemia/infarction, atrophy and normal MRI were found in Group-II. MRI brain in patients with neurological deficit and psychiatric disorder were not much different in both the groups. Conclusion: We found no statistically significant differences in frequencies of MRI brain abnormalities in SLE patients with and without aPL antibodies. Each of the three aPL may have a variable effect on the brain. PMID:26649010

  8. Multi-User Space Link Extension (SLE) System

    NASA Technical Reports Server (NTRS)

    Perkins, Toby

    2013-01-01

    The Multi-User Space (MUS) Link Extension system, a software and data system, provides Space Link Extension (SLE) users with three space data transfer services in timely, complete, and offline modes as applicable according to standards defined by the Consultative Committee for Space Data Systems (CCSDS). MUS radically reduces the schedule, cost, and risk of implementing a new SLE user system, minimizes operating costs with a lights-out approach to SLE, and is designed to require no sustaining engineering expense during its lifetime unless changes in the CCSDS SLE standards, combined with new provider implementations, force changes. No software modification to MUS needs to be made to support a new mission. Any systems engineer with Linux experience can begin testing SLE user service instances with MUS starting from a personal computer (PC) within five days. For flight operators, MUS provides a familiar-looking Web page for entering SLE configuration data received from SLE. Operators can also use the Web page to back up a space mission's entire set of up to approximately 500 SLE service instances in less than five seconds, or to restore or transfer from another system the same amount of data from a MUS backup file in about the same amount of time. Missions operate each MUS SLE service instance independently by sending it MUS directives, which are legible, plain ASCII strings. MUS directives are usually (but not necessarily) sent through a TCP-IP (Transmission Control Protocol Internet Protocol) socket from a MOC (Mission Operations Center) or POCC (Payload Operations Control Center) system, under scripted control, during "lights-out" spacecraft operation. MUS permits the flight operations team to configure independently each of its data interfaces; not only commands and telemetry, but also MUS status messages to the MOC. Interfaces can use single- or multiple-client TCP/IP server sockets, TCP/IP client sockets, temporary disk files, the system log, or standard in

  9. Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with Systemic Lupus Erythematosus

    PubMed Central

    López-López, Linnette; Nieves-Plaza, Mariely; Castro, María del R.; Font, Yvonne M.; Torres-Ramos, Carlos; Vilá, Luis M.; Ayala-Peña, Sylvette

    2014-01-01

    Objective To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients. Methods A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson’s chi-square test (or Fisher’s exact test) as appropriate. Results Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage. Conclusion PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE. PMID:24899636

  10. Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

    PubMed

    Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C

    2016-06-15

    T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

  11. Patient-reported outcomes in lupus clinical trials with biologics.

    PubMed

    Annapureddy, N; Devilliers, H; Jolly, M

    2016-09-01

    Therapeutic advances in systemic lupus erythematosus (SLE) are greatly needed. Despite advances in our knowledge of pathogenesis of the disease and targets, treatment remains a significant challenge. Finding effective and relatively safe medications remains one of the top priorities. SLE significantly impairs quality of life (QoL), and patient-reported outcomes (PROs) measure a unique aspect of the disease not captured by disease activity. Inclusion of PRO measurements is encouraged in SLE clinical trials, as they allow capturing benefits of a proposed intervention in language patients can relate to and in areas deemed pertinent and important to and by patients. Availability of patient-reported and patient-centric clinical trials data may facilitate patients in informed and shared decision making, and allow for comparative cost-effectiveness evaluation for future resource allocation and reimbursements. Herein we review clinical trials with biologic therapies wherein PRO tools were included in the study design. PMID:27497256

  12. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients.

    PubMed

    López, Patricia; de Paz, Banesa; Rodríguez-Carrio, Javier; Hevia, Arancha; Sánchez, Borja; Margolles, Abelardo; Suárez, Ana

    2016-01-01

    Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from naïve CD4(+) lymphocytes to a greater extent than healthy control-microbiota. Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4(+) lymphocyte over-activation, thus supporting a possible therapeutic benefit of probiotics containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3(+) IL-17(+) populations, suggesting a possible Treg-Th17 trans-differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL-17(+) populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNγ, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti-dsDNA titers were increased and showed a strong negative correlation with IL-6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine. PMID:27044888

  13. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients

    PubMed Central

    López, Patricia; de Paz, Banesa; Rodríguez-Carrio, Javier; Hevia, Arancha; Sánchez, Borja; Margolles, Abelardo; Suárez, Ana

    2016-01-01

    Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from naïve CD4+ lymphocytes to a greater extent than healthy control-microbiota. Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4+ lymphocyte over-activation, thus supporting a possible therapeutic benefit of probiotics containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3+ IL-17+ populations, suggesting a possible Treg-Th17 trans-differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL-17+ populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNγ, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti-dsDNA titers were increased and showed a strong negative correlation with IL-6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine. PMID:27044888

  14. Bacillus thuringiensis peptidoglycan hydrolase SleB171 involved in daughter cell separation during cell division.

    PubMed

    Li, Hua; Hu, Penggao; Zhao, Xiuyun; Yu, Ziniu; Li, Lin

    2016-04-01

    Whole-genome analyses have revealed a putative cell wall hydrolase gene (sleB171) that constitutes an operon with two other genes (ypeBandyhcN) of unknown function inBacillus thuringiensisBMB171. The putative SleB171 protein consists of 259 amino acids and has a molecular weight of 28.3 kDa. Gene disruption ofsleB171in the BMB171 genome causes the formation of long cell chains during the vegetative growth phase and delays spore formation and spore release, although it has no significant effect on cell growth and the ultimate release of the spores. The inseparable vegetative cells were nearly restored through the complementation ofsleB171expression. Real-time quantitative polymerase chain reaction analysis revealed thatsleB171is mainly active in the vegetative growth phase, with a maximum activity at the early stationary growth phase. Western blot analysis also confirmed thatsleB171is preferentially expressed during the vegetative growth phase. These results demonstrated that SleB171 plays an essential role in the daughter cell separation during cell division. PMID:26922318

  15. IgA nephropathy in systemic lupus erythematosus patients: case report and literature review.

    PubMed

    da Silva, Leonardo Sales; Almeida, Bruna Laiza Fontes; de Melo, Ana Karla Guedes; de Brito, Danielle Christine Soares Egypto; Braz, Alessandra Sousa; Freire, Eutília Andrade Medeiros

    2016-01-01

    Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear fine speckled pattern, and anticardiolipin IgM and 280U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non-SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in both the short and long terms. PMID:27267646

  16. Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

    PubMed

    Ardoin, S P; Schanberg, L E; Sandborg, C; Yow, E; Barnhart, H X; Mieszkalski, K l; Ilowite, N T; von Scheven, E; Eberhard, A; Levy, D M; Kimura, Y; Silverman, E; Bowyer, S L; Punaro, L; Singer, N G; Sherry, D D; McCurdy, D; Klein-Gitelman, M; Wallace, C; Silver, R; Wagner-Weiner, L; Higgins, G C; Brunner, H I; Jung, L K; Imundo, L; Soep, J B; Reed, A M

    2010-10-01

    As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of

  17. Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases

    PubMed Central

    Jovanovic, Vojislav; Teo, Boon Wee; Mak, Anselm; Thumboo, Julian; McKinney, Eoin F; Lee, James C; MacAry, Paul; Kemeny, David M; Jayne, David RW; Fong, Kok Yong; Lyons, Paul A; Smith, Kenneth GC

    2016-01-01

    Objectives Type 1 interferons (IFN-1) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-1 on mixed cell populations. We aimed to define modules of IFN-1-associated genes in purified leucocyte populations and use these as a basis for a detailed comparative analysis. Methods CD4+ and CD8+ T cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers and gene expression then determined by microarray. Modules of IFN-1-associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed. Results 1150 of 1288 IFN-1-associated genes were specific to myeloid subsets, compared with 11 genes unique to T cells. IFN-1 genes were more highly expressed in myeloid subsets compared with T cells. A subset of neutrophil samples from healthy volunteers (HV) and conditions not classically associated with IFN-1 signatures displayed increased IFN-1 gene expression, whereas upregulation of IFN-1-associated genes in T cells was restricted to SLE. Conclusions Given the broad upregulation of IFN-1 genes in neutrophils including in some HV, investigators reporting IFN-1 signatures on the basis of whole blood samples should be cautious about interpreting this as evidence of bona fide IFN-1-mediated pathology. Instead, specific upregulation of IFN-1-associated genes in T cells may be a useful biomarker and a further mechanism by which elevated IFN-1 contributes to autoimmunity in SLE. PMID:27252891

  18. Clinical Analysis of 61 Systemic Lupus Erythematosus Patients With Intestinal Pseudo-Obstruction and/or Ureterohydronephrosis

    PubMed Central

    Xu, Na; Zhao, Jiuliang; Liu, Jinjing; Wu, Di; Zhao, Lidan; Wang, Qian; Hou, Yong; Li, Mengtao; Zhang, Wen; Zeng, Xuejun; Fang, Weigang; Huang, Xiaoming; Zhang, Xuan; Tian, Xinping; Zhao, Yan; Zeng, Xiaofeng; Zhang, Fengchun

    2015-01-01

    Abstract The objective of this article is to investigate the clinical features of intestinal pseudo-obstruction (IPO) and/or ureterohydronephrosis in systemic lupus erythematosus (SLE). Sixty-one SLE patients with IPO and/or ureterohydronephrosis were analyzed retrospectively. A total of 183 cases were randomly selected as controls from 3840 SLE inpatients without IPO and ureterohydronephrosis during the same period. Patients were assigned to 1 of the 3 groups (SLE with IPO and ureterohydronephrosis, SLE with IPO, and SLE with ureterohydronephrosis). The clinical characteristics, treatments, and prognosis were compared between the 3 groups. There were 57 females and 4 males, with a mean age of 32.0 years. IPO was the initial manifestation of SLE in 49.1% of the cases, whereas ureterohydronephrosis in 32.5%. All patients were initially treated with a high-dose steroid. Thirty-one of these patients (50.8%) also received intravenous methylprednisolone pulse therapy. Two patients died of bowel perforation and lupus encephalopathy, and the other 59 patients (96.7%) achieved remission after treatment. The incidences of fever, glomerulonephritis, nervous system involvement, serositis, erythrocyte sedimentation rate elevation, hypoalbuminemia, hypocomplementemia, and anti-SSA antibody positivity were significantly higher in patients with IPO and/or ureterohydronephrosis than in the control group (without IPO and ureterohydronephrosis). Also, patients with IPO and/or ureterohydronephrosis had higher SLE Disease Activity Index scores than control patients. Compared with SLE patients with IPO, the patients with IPO and ureterohydronephrosis had a significantly higher incidence of gallbladder wall thickening, biliary tract dilatation, and serositis, whereas the patients with ureterohydronephrosis had less mucocutaneous involvement and serositis. Eight of the 47 IPO patients who initially responded well to immunotherapy relapsed; however, all responded well to retreatment with

  19. Localization of radiolabeled anti-DNA monoclonal antibodies in murine systemic lupus erythematosus (SLE)

    SciTech Connect

    Wahl, R.; Hahn, B.; Ebling, F.

    1984-01-01

    The diagnosis of SLE can be extremely difficult. This multi-system disease is characterized by the deposition of DNA-anti-DNA antibody (Ab) complexes in many tissues, producing glomerulonephritis and systemic vasculitis. This study evaluates an IGG monoclonal (Mo) Ab directe3d against DNA (MrSSl) for potential radioimmunodiagnosis of SLE. Six 15 wk. old F-1 female hybrids of NZB+NZW mice (an animal SLE model that develops vasculitis and nephritis) were injected with 50 ..mu..Cl of I-131 MrSSl and 15 ..mu..Cl of I-125 isotype-matched control mouse myeloma (LPC-1) (non-reactive with DNA). Imaging and tissue distribution were studied. Two animals were also imaged using I-131 LPC Ab. Images at 2 and 9 days showed no clear differences in scan patterns using MrSSl or LPC-1 Ab. Tissue distribution studies at six days, however, showed a significantly higher accumulation of MrSSl in the kidneys vs. control Ab (2.7% vs. 1.8% of injected dose) (p < .04). Similarly, higher levels of MrSS were also seen in the spleen, liver and lungs (p < .03). Blood levels tended to be higher with the specific antibody as well. These differences were not apparent at 3 days post injection. The increased concentration of MrSSl present at 9 days in several organs may be secondary to MrSSl binding to DNA containing immune complexes present in diseased tissues. Blocked clearance by immune complexes or DNA, or differences in electrical charges of the antibodies could be contributing to the higher MrSSl levels seen. Images did not suggest deiodination as responsible. Further studies are necessary to determine if the amount of MrSSl retained by diseased animals is indicative of SLE disease activity.

  20. Childhood onset systemic lupus erythematosus: how is it different from adult SLE?

    PubMed

    Aggarwal, Amita; Srivastava, Puja

    2015-02-01

    About 20% of systemic lupus erythematosus (SLE) starts in childhood and children have less gender bias in favor of females as compared to adults. Systemic manifestations, nephritis, neuro-psychiatric disease and cytopenias are more common in children at presentation than adults. Since most children develop lupus in their early adolescence, dealing with the diagnosis of an unpredictable lifelong disease during this phase of life is challenging. Physicians must recognise specific medical and social needs of this age group, for optimal long-term outcome. Steroids and immunosuppressive drugs are the cornerstone for treatment in children as with adults with lupus. The outcome has improved considerably with these drugs and 10-year survival is nearly 90%. Due to longer life spans more damage accrues in children as compared to adults. Most of the drugs are associated with significant toxicity and the goal of having a drug which reduces disease activity and damage without hampering normal growth, development and fertility is still an elusive one. The current review focuses on clinical and immunological aspects of childhood SLE and how it differs from adulthood SLE. PMID:24965742

  1. Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus.

    PubMed Central

    Patrono, C; Ciabattoni, G; Remuzzi, G; Gotti, E; Bombardieri, S; Di Munno, O; Tartarelli, G; Cinotti, G A; Simonetti, B M; Pierucci, A

    1985-01-01

    We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy. PMID:3900132

  2. Drug repositioning in SLE: crowd-sourcing, literature-mining and Big Data analysis.

    PubMed

    Grammer, A C; Ryals, M M; Heuer, S E; Robl, R D; Madamanchi, S; Davis, L S; Lauwerys, B; Catalina, M D; Lipsky, P E

    2016-09-01

    Lupus patients are in need of modern drugs to treat specific manifestations of their disease effectively and safely. In the past half century, only one new treatment has been approved by the US Food and Drug Administration (FDA) for systemic lupus erythematosus (SLE). In 2014-2015, the FDA approved 71 new drugs, only one of which targeted a rheumatic disease and none of which was approved for use in SLE. Repositioning/repurposing drugs approved for other diseases using multiple approaches is one possible means to find new treatment options for lupus patients. "Big Data" analysis approaches this challenge from an unbiased standpoint whereas literature mining and crowd sourcing for candidates assessed by the CoLTs (Combined Lupus Treatment Scoring) system provide a hypothesis-based approach to rank potential therapeutic candidates for possible clinical application. Both approaches mitigate risk since the candidates assessed have largely been extensively tested in clinical trials for other indications. The usefulness of a multi-pronged approach to drug repositioning in lupus is highlighted by orthogonal confirmation of hypothesis-based drug repositioning predictions by "Big Data" analysis of differentially expressed genes from lupus patient samples. The goal is to identify novel therapies that have the potential to affect disease processes specifically. Involvement of SLE patients and the scientists that study this disease in thinking about new drugs that may be effective in lupus though crowd-sourcing sites such as LRxL-STAT (www.linkedin.com/in/lrxlstat) is important in stimulating the momentum needed to test these novel drug targets for efficacy in lupus rapidly in small, proof-of-concept trials conducted by LuCIN, the Lupus Clinical Investigators Network (www.linkedin.com/in/lucinstat). PMID:27497259

  3. The NOD mouse as a model of SLE.

    PubMed

    Silveira, P A; Baxter, A G

    2001-01-01

    In addition to developing a high incidence of type 1 diabetes caused by a specific autoimmune response against pancreatic beta cells in the islets of Langerhans, NOD mice also demonstrate spontaneous autoimmunity to other targets including the thymus, adrenal gland, salivary glands, thyroid, testis, nuclear components and red blood cells. Moreover, treatment of pre-diabetic NOD mice with an intravenous dose of heat killed Mycobacterium bovis (M. bovis; bacillus Calmette-Guèrin (BCG)) protects them from developing type 1 diabetes, but instead precipitates an autoimmune rheumatic disease similar to systemic lupus erythematosus (SLE), characterised by accelerated and increased incidence of haemolytic anaemia (HA), anti-nuclear autoantibody (ANA) production, exacerbation of sialadenitis, and the appearance of immune complex-mediated glomerulonephritis (GN). The reciprocal switching between the two phenotypes by a single environmental trigger (mycobacterial exposure) raised the possibility that genetic susceptibility for type 1 diabetes and SLE may be conferred by a single collection of genes in the NOD mouse. This review will focus on the genetic components predisposing NOD mice to SLE induced by BCG treatment and compare them to previously determined diabetes susceptibility genes in this strain and SLE susceptibility genes in the BXSB, MRL and the New Zealand mouse strains. PMID:11681493

  4. Inhibition of adenovirus DNA synthesis in vitro by sera from patients with systemic lupus erythematosus

    SciTech Connect

    Horwitz, M.S.; Friefeld, B.R.; Keiser, H.D.

    1982-12-01

    Sera containing antinuclear antibodies from patients with systemic lupus erythematosus (SLE) and related disorders were tested for their effect on the synthesis of adenovirus (Ad) DNA in an in vitro replication system. After being heated at 60/sup 0/C for 1 h, some sera from patients with SLE inhibited Ad DNA synthesis by 60 to 100%. Antibodies to double-stranded DNA were present in 15 of the 16 inhibitory sera, and inhibitory activity copurified with anti-double-stranded DNA in the immunoglobulin G fraction. These SLE sera did not inhibit the DNA polymerases ..cap alpha.., BETA, ..gamma.. and had no antibody to the 72,000-dalton DNA-binding protein necessary for Ad DNA synthesis. The presence of antibodies to single-stranded DNA and a variety of saline-extractable antigens (Sm, Ha, nRNP, and rRNP) did not correlate with SLE serum inhibitory activity. Methods previously developed for studying the individual steps in Ad DNA replication were used to determine the site of inhibition by the SLE sera that contained antibody to double-stranded DNA. Concentrations of the SLE inhibitor that decreased the elongation of Ad DNA by greater than 85% had no effect on either the initiation of Ad DNA synthesis or the polymerization of the first 26 deoxyribonucleotides.

  5. TLR9-induced miR-155 and Ets-1 decrease expression of CD1d on B cells in SLE.

    PubMed

    Liu, Fei; Fan, Hongye; Ren, Deshan; Dong, Guanjun; Hu, Erling; Ji, Jianjian; Hou, Yayi

    2015-07-01

    B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE. In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells. Moreover, inflammation-related microRNA-155 (miR-155) negatively correlated with the expression of CD1d in B cells. miR-155 directly targeted the 3'-untranslated region (3'-UTR) of CD1d upon TLR9 activation in both humans and mice. The inhibitory effects of miR-155 on CD1d expression in B cells impaired their antigen-presenting capacity to iNKT cells. In addition, Ets-1, a susceptibility gene of SLE, also directly regulated the expression of the CD1d gene at the transcriptional level. These findings provide new insight into the mechanism underlying decreased CD1d expression on B cells in SLE, suggesting that inhibition of inflammation may increase CD1d expression in B cells to ameliorate SLE via modulating iNKT cells. PMID:25929465

  6. Sialyltransferase and Neuraminidase Levels/Ratios and Sialic Acid Levels in Peripheral Blood B Cells Correlate with Measures of Disease Activity in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Pilot Study

    PubMed Central

    Liou, Lieh-bang; Huang, Che-ching

    2016-01-01

    Objective We attempted to determine whether the level of enzymes sialyltransferase (ST) and neuraminidase (Neu) and sialic acid (SIA) in patients with systemic lupus erythematosus (SLE) correlates with the SLE Disease Activity Index (SLEDAI) and in patients with rheumatoid arthritis (RA) correlates with the Disease Activity Score28 (DAS28). Methods We examined cell-surface levels of ST6Gal-1, Neu1, ST3Gal-1, Neu3, α-2,6-SIA, and α-2,3-SIA by using fluorescent anti-enzyme antibodies, fluorescent-conjugated Sambucus nigra lectin, and fluorescent-conjugated Maackia amurensis lectin on blood cells in SLE and RA patients and assessed correlations of these levels with SLEDAI and with DAS28. Areas under the curve (AUC) were calculated for different variables against SLEDAI. Results The B-cell ST3Gal-1/Neu3 ratio positively correlated with SLEDAI scores (ρ = 0.409 and P = 0.002, statistically significant after Bonferroni’ correction for multiple analyses.). It was supported by the inverse correlation of B-cell Neu3 levels with SLEDAI scores (ρ = −0.264, P = 0.048). The B-cell ST3Gal-1/Neu3 ratio against SLEDAI yielded an AUC of 0.689, which was comparable to that of anti-dsDNA levels at 0.635. In contrast, both ST3Gal-1 and Neu3 levels of RA B cells (r = 0.376, P = 0.013; r = 0.425, P = 0.005, respectively) correlated positively with high disease-activity DAS28 scores. Conclusion B-cell ST3Gal-1/Neu3 ratios in SLE and B-cell ST3Gal-1 and Neu3 levels in RA with high disease-activity DAS28 scores correlated with disease activity measures and may be useful in monitoring disease activities. PMID:26981635

  7. Understanding remission in real-world lupus patients across five European countries.

    PubMed

    Schneider, M; Mosca, M; Pego-Reigosa, J M; Hachulla, E; Teh, L-S; Perna, A; Koscielny, V; Pike, J; Lobosco, S; Apolone, G

    2016-04-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased mortality and significant personal, psychological and socioeconomic consequences. An agreed definition of remission is needed and lacking. We sought to visualize 'remission in SLE' in European patients considered by their physicians to be 'in remission' by comparing the reported symptom burden as reported by treating physicians for patients considered to be 'in remission' and those not considered to be 'in remission'. Data for 1227 patients drawn from a multinational, real-world survey of patients with SLE consulting practising rheumatologists and nephrologists in France, Germany, Italy, Spain, and the UK show that physicians classed their patients as 'in remission' despite a considerable ongoing symptom burden and intensive immunosuppressive medication. Patients considered to be 'in remission' still had a mean of 2.68 current symptoms vs 5.48 for those considered to be not 'in remission' (p < 0.0001). The most common symptoms among those seen to be 'in remission' were joint symptoms, fatigue, pain, mucocutaneous involvement, haematological manifestations and kidney abnormalities. The current analysis highlights important ongoing disease activity, symptom burden and immunosuppressive medication in European patients with SLE considered by their treating physician to be 'in remission'. For a further improvement of outcome, there is an urgent need for an international consensus on the definitions for remission among patients with SLE. PMID:26635245

  8. Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

    SciTech Connect

    Moroz, L.A.; MacLean, L.D.; Langleben, D.

    1986-09-15

    Fibrinolytic activities of whole blood and plasma were determined by /sup 125/I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism.

  9. Antinuclear antibodies in patients on anticonvulsant therapy

    PubMed Central

    Alarcón-Segovia, D.; Fishbein, Eugenia; Reyes, P. A.; Díes, H.; Shwadsky, S.

    1972-01-01

    Antinuclear antibodies to calf thymus nuclei, NP, DNA, sDNA, sNP and Sm antigen were investigated in sera from 170 patients on various programmes of prolonged anticonvulsant treatment. Findings were compared to those on 214 tuberculous patients on isoniazid, 109 SLE patients and 66 healthy subjects. Patients on anticonvulsants had a significantly higher incidence of ANA to DNA, sDNA, sNP and Sm antigen than the controls but had a lower incidence of ANA to all antigens, except sNP, than the SLE patients. Patients on isoniazid did not have DNA antibodies, but had antibodies to whole nuclei and to NP which were practically absent in the anticonvulsant group. Of all patients on anticonvulsants only those receiving hydantoins had ANA to Sm antigen, while those receiving only primidone had antibodies to sNP but no antibodies to DNA. Alteration of sNP with isoniazid did not result in an increased incidence of ANA in the anticonvulsant group as it does in isoniazid treated subjects. It is concluded that the SLE-activating properties of diverse anticonvulsants probably resides in their potential to induce ANA. Although all anticonvulsants elicit ANA directed primarily to sNP, each may do so by different mechanisms or by altering different sites in the sNP molecule. The mechanisms by which anticonvulsant and isoniazid intake results in ANA probably differ. Presence of DNA antibodies in some patients on anticonvulsants may indicate that their convulsions were due to SLE. PMID:4117275

  10. Genetic Association of CD247 (CD3ζ) with SLE in a Large-Scale Multiethnic Study

    PubMed Central

    Martins, Madalena; Williams, Adrienne H.; Comeau, Mary; Marion, Miranda; Ziegler, Julie T.; Freedman, Barry I.; Merrill, Joan T.; Glenn, Stuart B.; Kelly, Jennifer A.; Sivils, Kathy M.; James, Judith A.; Guthridge, Joel M.; Alarcón-Riquelme, Marta E.; Bae, Sang-Cheol; Kim, Jae-Hoon; Kim, Dam; Anaya, Juan-Manuel; Boackle, Susan A.; Criswell, Lindsey A.; Kimberly, Robert P.; Alarcón, Graciela S.; Brown, Elizabeth E.; Vilá, Luis M.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Niewold, Timothy B.; Tsao, Betty P.; Gilkeson, Gary S.; Kamen, Diane L.; Jacob, Chaim O.; Stevens, Anne M.; Gaffney, Patrick M.; Harley, John B.; Langefeld, Carl D.; Fesel, Constantin

    2015-01-01

    A classic T-cell phenotype in Systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters TCR signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multi-ethnic population. We typed 44 contiguous CD247 SNPs in 8 922 SLE patients and 8 077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99×10−4SLE with CD247, which is shared by various autoimmune disorders and supports a common T cell-mediated mechanism. PMID:25569266

  11. Genetic and Physical Interaction of the B-Cell SLE-Associated Genes BANK1 and BLK

    PubMed Central

    Castillejo-López, Casimiro; Delgado-Vega, Angélica M.; Wojcik, Jerome; Kozyrev, Sergey V.; Thavathiru, Elangovan; Wu, Ying-Yu; Sánchez, Elena; Pöllmann, David; López-Egido, Juan R.; Fineschi, Serena; Domínguez, Nicolás; Lu, Rufei; James, Judith A.; Merrill, Joan T.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Moser, Kathy; Gilkeson, Gary; Frostegård, Johan; Pons-Estel, Bernardo A.; D’Alfonso, Sandra; Witte, Torsten; Callejas, José Luis; Harley, John B.; Gaffney, Patrick; Martin, Javier; Guthridge, Joel M.; Alarcón-Riquelme, Marta E.

    2012-01-01

    Objectives Altered signaling in B-cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signaling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterize the role of BANK1 and BLK in SLE, we performed a genetic interaction analysis hypothesizing that genetic interactions could reveal functional pathways relevant to disease pathogenesis. Methods We Used the method GPAT16 to analyze the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localization, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. Results Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from Northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, we tested the possibility that BANK1 and BLK could also show a protein-protein interaction. We demonstrated co-immunoprecipitation and co-localization of BLK and BANK1. In a Daudi cell line and primary naïve B-cells the endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. Conclusions Here, we show a genetic interaction between BANK1 and BLK, and demonstrate that these molecules interact physically. Our results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signaling pathway. PMID:21978998

  12. WHY CAN’T WE FIND A NEW TREATMENT FOR SLE?

    PubMed Central

    Eisenberg, Robert

    2009-01-01

    No new therapy for systemic lupus erythematosus has been approved. In the last decade, the development of several novel compounds has been pursued for lupus, but so far nothing has been proven to be effective. This review discusses some of the reasons why it may be so difficulty to demonstrate that a novel therapy is effective for this disease. These include the complexity of the disease itself; the lack of reliable outcome measures; our limited understanding of the pathogenesis of the disease; the propensity of lupus patients to have bad outcomes and to react to medicines in unusual ways; the heterogeneity of the patient population; the unpredictable course of disease in individual patients; and the lack of reliable biomarkers. Although some of the tested targeted compounds that are apparently based on strong preclinical and mechanistic data may indeed not be effective therapies for SLE, it is hard not to believe that among the various specific agents now being tested that at least some of them should downregulate the abnormal immunoregulation characteristic of SLE, and thus be clinically effective. We need to be persistent and imaginative in identifying these effective agents and proving their efficacy so that they may be widely used in our lupus populations. PMID:19329279

  13. Development and validation of a simple lupus severity index using ACR criteria for classification of SLE

    PubMed Central

    Bello, Ghalib A; Brown, Michael A; Kelly, Jennifer A; Thanou, Aikaterini; James, Judith A; Montgomery, Courtney G

    2016-01-01

    Objective To develop a simple systemic lupus erythematosus (SLE) severity index that requires knowledge of only American College of Rheumatology (ACR) criteria and subcriteria. Methods This study used demographic, mortality and medical records data of 1915 patients with lupus from the Lupus Family Registry and Repository. The data were randomly split (2:1 ratio) into independent training and validation sets. A logistic regression with ridge penalty was used to model the probability of being prescribed major immunosuppressive drugs—a surrogate indicator of lupus severity. ACR criteria and subcriteria were used as predictor variables in this model, and the resulting regression coefficient estimates obtained from the training data were used as item weightings to construct the severity index. Results The resulting index was tested on the independent validation dataset and was found to have high predictive accuracy for immunosuppressive use and early mortality. The index was also found to be strongly correlated with a previously existing severity score for lupus. In addition, demographic factors known to influence lupus severity (eg, age of onset, gender and ethnicity) all showed robust associations with our severity index that were consistent with observed clinical trends. Conclusions This new index can be easily computed using ACR criteria, which may be among the most readily available data elements from patient medical records. This tool may be useful in lupus research, especially large dataset analyses to stratify patients by disease severity, an important prognostic indicator in SLE. PMID:27026812

  14. Clinical Analysis of 56 Patients with Rhupus Syndrome: Manifestations and Comparisons with Systemic Lupus Erythematosus

    PubMed Central

    Li, Jing; Wu, Honghua; Huang, Xinxiang; Xu, Dong; Zheng, Wenjie; Zhao, Yan; Liu, Wanli; Zeng, Xiaofeng

    2014-01-01

    Abstract To investigate the clinical features of Rhupus syndrome, we retrospectively reviewed the medical records of 56 patients with Rhupus who were hospitalized at the Peking Union Medical College Hospital, Beijing, China, between January 2000 and March 2013. We analyzed the clinical manifestations of Rhupus syndrome and compared these with a control group of 160 randomly selected systemic lupus erythematosus (SLE) patients without coexisting rheumatoid arthritis (RA). In our center, 1.30% (56/4301) of hospitalized SLE patients had Rhupus syndrome. The median disease duration was 8.0 years and 83.9% had RA onset. All Rhupus patients showed radiological erosion in the joints. Compared with the control group, Rhupus patients had a longer disease duration, higher prevalence of anticyclic citrullinated peptide antibody and rheumatoid factor, higher incidence of symmetrical polyarthritis with more joint deformities and rheumatic nodules, and increased erythrocyte sediment rate and c-reactive protein levels (P < 0.005). In addition, a lower SLE disease activity index and incidences of malar rash, hemolytic anemia, renal and neurological involvement (P < 0.005), and hypocomplementemia (P < 0.05) was observed in the Rhupus group. Rhupus syndrome is rare in SLE patients. Most Rhupus patients had RA onset and a distinctive clinical profile characterized by more severe RA-associated and mild SLE-associated damage. Specific autoantibodies and imaging findings could be helpful for making accurate Rhupus diagnoses. PMID:25170930

  15. Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

    PubMed Central

    Zhao, Peiqing; Xu, Liyun; Wang, Piming; Liang, Xiaohong; Qi, Jianni; Liu, Peng; Guo, Chun; Zhang, Lining; Ma, Chunhong; Gao, Lifen

    2010-01-01

    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. Innate and adaptive immunity cooperatively contribute to the development of SLE. Antigen-presenting cells (APCs) have been suggested to link innate and adaptive immunity. T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4; also known as Timd4), expressed primarily on the surface of APCs, is a member of the TIM family, a recently described group of molecules that have received much attention as potential regulators of the immune system. In this study, we used quantitative real-time reverse transcription-polymerase chain reaction to examine the mRNA expression of Tim-4 in peripheral blood mononuclear cells (PBMCs) from SLE patients and further analyzed the correlation between the expression of Tim-4 and Tim-1 (a potential ligand for Tim-4) in PBMCs and serum tumor necrosis factor (TNF)-α levels. The results showed that Tim-4 mRNA expression in PBMCs was significantly higher in SLE patients than in healthy controls, especially those patients in the active phase of disease. Moreover, Tim-4 mRNA levels were closely correlated with Tim-1 mRNA levels in PBMCs and with serum TNF-α levels in SLE patients but not in the control group. Taken together, these results demonstrate that Tim-4 may be involved in the pathogenesis of SLE. PMID:20140011

  16. Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus.

    PubMed

    Liu, Yuxin; Yu, Jianghong; Oaks, Zachary; Marchena-Mendez, Ivan; Francis, Lisa; Bonilla, Eduardo; Aleksiejuk, Phillip; Patel, Jessica; Banki, Katalin; Landas, Steve K; Perl, Andras

    2015-10-01

    Liver disease (LD), defined as ≥ 2-fold elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), was examined in a longitudinal study of systemic lupus erythematosus (SLE) patients. Among 435 patients, 90 (20.7%) had LD with a greater prevalence in males (15/39; 38.5%) than females (75/396; 18.9%; p = 0.01). SLE disease activity index (SLEDAI) was greater in LD patients (7.8 ± 0.7) relative to those without (5.8 ± 0.3; p = 0.0025). Anti-smooth muscle antibodies, anti-DNA antibodies, hypocomplementemia, proteinuria, leucopenia, thrombocytopenia, and anti-phospholipid syndrome were increased in LD. An absence of LD was noted in patients receiving rapamycin relative to azathioprine, cyclosporine A, or cyclophosphamide. An absence of LD was also noted in patients treated with N-acetylcysteine. LFTs were normalized and SLEDAI was diminished with increased prednisone use in 76/90 LD patients over 12.1 ± 2.6 months. Thus, LD is attributed to autoimmunity and disease activity, it responds to prednisone, and it is potentially preventable by rapamycin or N-acetylcysteine treatment. PMID:26160213

  17. Relationship between QT Interval Length and Arterial Stiffness in Systemic Lupus Erythematosus (SLE): A Cross-Sectional Case-Control Study

    PubMed Central

    Rivera-López, Ricardo; Jiménez-Jáimez, Juan; Sabio, José Mario; Zamora-Pasadas, Mónica; Vargas-Hitos, José Antonio; Martínez-Bordonado, Josefina; Navarrete-Navarrete, Nuria; Fernández, Ricardo Rivera; Sanchez-Cantalejo, E.; Jiménez-Alonso, Juan

    2016-01-01

    Introduction and Objectives The QT interval on the electrocardiogram has been shown to be longer in patients with systemic lupus erythematosus (SLE) compared to that of the general population. The clinical significance of this finding is unknown. The aim of this study was to assess the relationship between QT interval and subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. Material and Methods 93 patients with SLE and 109 healthy women with similar basal characteristics were studied. All patients underwent a 12- lead electrocardiogram, and corrected QT interval (QTc) was measured using the Bazett’s formula. The presence of atherosclerosis was evaluated by carotid-femoral pulse-wave velocity. Results Clinical basal characteristics were similar in both groups. QTc interval was 415±21.4 milliseconds in all patients, and 407±19.1 milliseconds in the control group (p = 0.007). There was a positive correlation between QTc interval and carotid-femoral pulse-wave velocity (r = 0.235; p = 0.02) in patients with SLE. This association was independent of hypertension and age in a multivariate analysis. Conclusion QTc interval measured by electrocardiogram is prolonged in SLE patients; it is related to subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. This measure may help stratify risk in routine clinical practice and select the patients that might benefit from a more aggressive therapy in the prevention of cardiovascular events. PMID:27064990

  18. Methyl-CpG-Binding Protein 2 (MECP2) Polymorphism in Iranian Patients with Systemic Lupus Erythematosus.

    PubMed

    Alesaeidi, Samira; Karami, Jafar; Mahmoudi, Mahdi; Akbarian, Mahmoud; Poursani, Shiva; Amirzadeh, Azadeh; Haddadi, Nazgol-Sadat; Saffari, Elahe; Jamshidi, Ahmad Reza

    2015-12-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which involves many organs and presents with various symptoms. It has been shown that genetic and environmental factors play a major role in this disease and may affect the onset, activity, damage, and mortality of the disease. According to recent studies, methyl-CpG-binding protein 2 (MECP2) has been associated with SLE in various populations. Herein, we studied MECP2 polymorphism in Iranian lupus patients and controls. The study included a total of 884 samples of Iranian ancestry (492 independent SLE patients and 392 unrelated healthy controls). Healthy controls were gender-, ethnic-, and age-matched with the patients. Patient and control samples were genotyped for rs1734787, rs1734791, rs1734792, and rs17435 by applying the Allelic Discrimination Real-Time PCR System. Our results showed a significant association between rs1734787 and rs1734791 SNPs and the risk of SLE in the Iranian population (p = 0.028, p = 0.028), but did not show any significant association with rs1734792 and rs17435 SNPs (p = 075, p = 0.75). The rs1734787 C and the rs1734791 T allele frequencies in the patients were significantly higher than the control group (p = 0.014, p = 0.012). In addition, a significant CTAT haplotype frequency was observed in cases with SLE (p = 0.012), and a significant AAAT haplotype frequency was observed in the control group (p = 0.0003). However, there was no significant association between genotype frequencies and SLE patients. Also, there was no significant association between these SNPs and clinical features. The result of this study suggests that polymorphism in the MECP2 locus is associated with the susceptibility of Iranian SLE patients. PMID:26156810

  19. Elevated Salivary Alpha-Amylase Level, Association Between Depression and Disease Activity, and Stress as a Predictor of Disease Flare in Systemic Lupus Erythematosus

    PubMed Central

    Jung, Ju-Yang; Nam, Jin-Young; Kim, Hyoun-Ah; Suh, Chang-Hee

    2015-01-01

    Abstract Psychological stress has been shown to trigger systemic lupus erythematosus (SLE). However, objective evidence of symptom aggravation due to mental stress is difficult to identify. We aimed to investigate the relationship between SLE disease activity and mental stress, and the usefulness of saliva as an assessment index for stress in patients with SLE. We prospectively assessed the salivary stress hormone and disease-related biomarkers, and questionnaire data regarding stress and depression in 100 patients with SLE and 49 sex- and age-matched normal controls (NCs). Patients with SLE had higher mean salivary α-amylase levels (5.7 ± 4.6 U/mL vs 2.7 ± 2.5 U/mL, P < 0.001), anti-chromatin antibody levels (25.3 ± 22.9 U/mL vs 15.9 ± 10.9 U/mL, P < 0.001), and Beck Depression Index (BDI) scores (11.1 ± 9.2 vs 5.3 ± 5.1, P < 0.001) than NCs. However, salivary cortisol levels and Perceived Stress Scale (PSS) scores did not differ between the groups. The BDI scores correlated with the SLE disease activity index (SLEDAI) scores (r = 0.253, P = 0.011) and erythrocyte sedimentation rates (r = 0.234, P = 0.019). SLE patients with the highest-quartile PSS scores had significantly increased SLEDAI scores compared to those with the lowest-quartile PSS scores after 4 to 5 months’ follow-up. Moreover, SLE patients with elevated SLEDAI scores had higher baseline PSS scores. Patients with SLE showed uncoupling of the sympathetic nervous system and hypothalamic–pituitary–adrenal axis; higher salivary α-amylase and no different cortisol levels compared with NCs. Also, patients with SLE were more depressed, which correlated with disease activity. Furthermore, perceived stress was not correlated with disease activity; however, disease activity worsened several months later with elevated perceived stress levels. PMID:26222848

  20. Pharmacokinetics, Pharmacodynamics, Safety, and Clinical Activity of Multiple Doses of RCT-18 in Chinese Patients With Systemic Lupus Erythematosus.

    PubMed

    Zhao, Qian; Chen, Xia; Hou, Yong; Jiang, Ji; Zhong, Wen; Yao, Xuejing; Wang, Wenxiang; Li, Lin; Fang, Jianmin; Zhang, Fengchun; Hu, Pei

    2016-08-01

    RCT-18 is a novel recombinant fusion protein that blocks the activity of a B-lymphocyte stimulator and a proliferation-inducing ligand. This was a randomized, single-blind, and placebo-controlled phase 1 study in 12 patients with systemic lupus erythematosus. Eligible patients were randomized 3:1 to receive multiple subcutaneous doses of RCT-18 for 4 weeks (180 mg, once weekly) or placebo and monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical activity. After multiple-dose RCT-18, the maximal serum concentration (Cmax ) of total and free RCT-18 was reached within 1 to 2 days. Mean elimination half-life for total RCT-18 and free RCT-18 was 11.4 to 26.4 days and 2.4 to 26.5 days, respectively. Slight accumulation was found after multiple subcutaneous administrations. The average accumulation ratios of AUC and Cmax after the fourth administration of RCT-18 were 2.0 and 1.7 for total RCT-18, and 1.8 and 1.6 for free RCT-18. The formation and elimination of BLyS-RCT-18 complex were much slower, with a time to Cmax of 14 to 46 days. Pharmacokinetic characteristics of RCT-18 in SLE patients were similar to those in patients with rheumatoid arthritis. No positive reaction was detected in the immunogenicity assessments. RCT-18 was biologically active, according to serum immunoglobulin and B-cell levels. Treatment-related IgM and IgA reduction was found during this study. CD19(+) , IgD(+) , and CD27(+) B-cell counts were increased after administration and decreased subsequently. SLE patients treated with RCT-18 were more prone to infections, including moderate and severe infections. Lower dosages of RCT-18 should be considered in further clinical development. PMID:26634642

  1. Prevalence of Hyposalivation in Patients with Systemic Lupus Erythematosus in a Brazilian Subpopulation

    PubMed Central

    Leite, Cristhiane Almeida; Galera, Marcial Francis; Espinosa, Mariano Martínez; de Lima, Paulo Ricardo Teles; Fernandes, Vander; Borges, Álvaro Henrique; Dias, Eliane Pedra

    2015-01-01

    Background. Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem, and autoimmune disease. Objective. The aim of this study was to describe the prevalence of hyposalivation in SLE patients and evaluate factors associated. Methods. This is a cross-sectional study developed at the Cuiaba University General Hospital (UNIC-HGU), Mato Grosso, Brazil. The study population consisted of female SLE patients treated at this hospital from 06/2010 to 12/2012. Unstimulated salivary flow rates (SFRs) were measured. Descriptive and inferential analyses were performed in all cases using a significance level P < 0.05. Results. The results showed that 79% of patients with systemic lupus erythematosus suffered from hyposalivation and that the disease activity and age in years were the factors that resulted in statistically significant differences. Conclusion. The activity of the disease, age >27 years, and the drugs used were factors associated with hyposalivation, resulting in a statistically significant decrease in saliva production. PMID:25649631

  2. Understanding and Managing Pregnancy in Patients with Lupus

    PubMed Central

    de Jesus, Guilherme Ramires; Mendoza-Pinto, Claudia; de Jesus, Nilson Ramires; dos Santos, Flávia Cunha; Klumb, Evandro Mendes; Carrasco, Mario García; Levy, Roger Abramino

    2015-01-01

    Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease that occurs predominantly in women of fertile age. The association of SLE and pregnancy, mainly with active disease and especially with nephritis, has poorer pregnancy outcomes, with increased frequency of preeclampsia, fetal loss, prematurity, growth restriction, and newborns small for gestational age. Therefore, SLE pregnancies are considered high risk condition, should be monitored frequently during pregnancy and delivery should occur in a controlled setting. Pregnancy induces dramatic immune and neuroendocrine changes in the maternal body in order to protect the fetus from immunologic attack and these modifications can be affected by SLE. The risk of flares depends on the level of maternal disease activity in the 6–12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception. It is a challenge to differentiate lupus nephritis from preeclampsia and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of successful pregnancies. PMID:26246905

  3. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays. PMID:27003157

  4. Signal transducer and activator of transcription 5 is implicated in disease activity in adult and juvenile onset systemic lupus erythematosus.

    PubMed

    Meshaal, Safa; El Refai, Rasha; El Saie, Ahmed; El Hawary, Rabab

    2016-06-01

    The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in humans. It is the principal signaling mechanism for a wide array of cytokines and growth factors. Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE). In this study, we tried to assess the role of STAT5 in systemic lupus erythematosus and correlate its phosphorylation level with the disease activity. The activation of the STAT5 was assessed by measuring the level of expression of phosphorylated STAT5 (pSTAT5) using flow cytometry on the peripheral blood T and B cells in 58 SLE patients (40 adult and 18 juvenile onset) and on 23 healthy age- and sex-matched controls for both groups. Serum prolactin level was also assessed in the patients and control by ELISA. The study revealed that the level of pSTAT5 was higher in adult SLE patients than in healthy control (p = 0.001) and in juvenile-onset SLE patients versus age-matched control (p = 0.031). A positive correlation existed between the pSTAT5 levels and Systemic Lupus Activity Measure (SLAM) score and also with multiple clinical manifestations indicating a potential role of STAT5 signaling in pathogenesis SLE. The pSTAT5 signaling is implicated in the disease activity of SLE and may be a useful target of therapy by correcting the dysregulation of cytokines involved in the disease pathogenesis. PMID:27041383

  5. Lack of cardiovascular risk assessment in inflammatory arthritis and systemic lupus erythematosus patients at a tertiary care center.

    PubMed

    Keeling, Stephanie O; Teo, Michelle; Fung, Daisy

    2011-10-01

    The purpose of this study is to evaluate cardiovascular risk assessment at a Canadian rheumatology center and describe the cardiovascular risk of inflammatory arthritis (IA) and systemic lupus erythematosus (SLE) patients using the Framingham risk score. A retrospective chart review of 504 patients attending nine rheumatology practices at the University of Alberta Hospital was performed. A pre-specified case report form detailed patient demographics, cardiac risk factors, variables for the Framingham 2008 score, disease activity, and medication use. In this group of 504 patients, 64 (12.7%) had SLE (male (M) to female (F) ratio = 60:4) and 440 (87.3%) had an IA (M to F ratio = 117:323). Of the SLE patients, 31 (48.4%) met four or more American College of Rheumatology (ACR) criteria, 33 (51.6%) had less than four ACR criteria. Of the IA patients, 156 (35.5%) were CCP positive and 257 (58.4%) were RF positive. Utilizing the chart data, retrospective Framingham risk scores were calculable for one (1.6%) SLE patient and three (0.68%) IA patients. The most common cardiac risk factors not documented in the medical records of both the SLE and IA patients included: (1) positive family history of MI, (2) diabetes, and (3) lipid status. The blood pressure was more frequently documented in the SLE patients (93.8%) compared to the IA patients (56.1%). While traditional cardiac risk factors only partially contribute to the increased cardiovascular risk in these patients, cardiovascular risk assessment was suboptimally performed amongst a large group of rheumatologists. A dedicated cardiovascular risk reduction clinic for inflammatory rheumatic diseases has been established at this site to fulfill this need and evaluate treatment strategies. PMID:21503617

  6. Serum nitrated nucleosome levels in patients with systemic lupus erythematosus: a retrospective longitudinal cohort study

    PubMed Central

    2014-01-01

    Introduction Circulating nucleosomes released from apoptotic cells are important in the pathogenesis of systemic lupus erythematosus (SLE). Both nucleosomes and anti-nucleosome antibodies are deposited in inflamed tissues in patients with SLE. Active inflammation promotes nitration of tyrosine residues on serum proteins. Our hypothesis was that levels of nitrated nucleosomes would be elevated in patients with SLE and could be associated with disease activity. We therefore carried out a retrospective longitudinal study to investigate factors affecting levels of nitrated nucleosomes (NN) in patients with SLE. Methods A novel serum ELISA was developed to measure serum NN and modified to measure serum nitrated albumin (NA). Levels of both NN and NA were measured in 397 samples from 49 patients with SLE followed through periods of disease flare and remission for a mean of 89 months. Anti-nucleosome antibody (anti-nuc) levels were measured in the same samples. The effects of 24 different clinical, demographic and serological variables on NN, NA and anti-nuc levels were assessed by univariable and multivariable analysis. Results Patients with SLE had higher mean NN than healthy controls or patients with other autoimmune rheumatic diseases (P =0.01). Serum samples from 18 out of 49 (36.7%) of SLE patients were never positive for NN. This group of 18 patients was characterized by lower anti-double stranded DNA antibodies (anti-dsDNA), disease activity and use of immunosuppressants. In the remaining 63.3%, NN levels were variable. High NN was significantly associated with anti-Sm antibodies, vasculitis, immunosuppressants, hydroxychloroquine and age at diagnosis. NN levels were raised in neuropsychiatric flares. NN levels did not completely parallel NA results, thus providing additional information over measuring nitration status alone. NN levels were not associated with anti-nuc levels. Conclusions NN are raised in a subset of patients with SLE, particularly those who are

  7. Resilience and Treatment Adhesion in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Faria, Daniella Antunes Pousa; Revoredo, Luciana Silva; Vilar, Maria José; Eulália Maria Chaves, Maia

    2014-01-01

    Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune, rheumatic inflammatory disease that can cause significant morbidity with evident psychological impacts and obvious harm to quality-of-life that require the patient to adapt treatment. Objective: Assessment of resilience and the self-reported treatment adhesion behaviors of patients with SLE, investigating which of these factors are associated to resilience. Method: Cross-sectional study of 40 women with SLE. A questionnaire with social demographic data, health history and the Wagnild Young Resilience Scale were used. Results: 62.5% followed the medical treatment properly but 55% found it difficult. 27.5% of the patients presented low resilience, 57.5% medium and 15% high resilience. Resilience was associated in the chi-square test (p-value < 0.05) with the variables work, understanding SLE, trying to find out about SLE, following the treatment correctly, difficulty in following the treatment and stopping some activity because of the disease. In the correlation analysis, resilience was associated with age (-0.3960), number of working hours (0.5533), specialized treatment duration (-0.8103) and disease duration from diagnosis (-0.8014). Conclusion: Patients with high resilience tended to follow treatment correctly, tried to understand the disease and adhered more to the treatment to avoid risks and promote protection factors. Therefore knowledge of resilience in patients with SLE is necessary. It is important that the state takes necessary actions to facilitate access to treatment, to educational programs and to medical support. Awareness and counselling sessions must be initiated to develop and promote individual capacities to learn how to tackle with the disease for which psychological support of family and doctors can play a significant role. PMID:24665352

  8. Incidence of and Risk Factors for Adverse Cardiovascular Events Among Patients With Systemic Lupus Erythematosus

    PubMed Central

    Magder, Laurence S.; Petri, Michelle

    2012-01-01

    Patients with systemic lupus erythematosus (SLE) are at excess risk of cardiovascular events (CVEs). There is uncertainty regarding the relative importance of SLE disease activity, medications, or traditional risk factors in this increased risk. To gain insight into this, the authors analyzed data from a cohort of 1,874 patients with SLE who were seen quarterly at a single clinical center (April 1987–June 2010) using pooled logistic regression analysis. In 9,485 person-years of follow-up, the authors observed 134 CVEs (rate = 14.1/1,000 person-years). This was 2.66 times what would be expected in the general population based on Framingham risk scores (95% confidence interval: 2.16, 3.16). After adjustment for age, CVE rates were not associated with duration of SLE. However, they were associated with average past levels of SLE disease activity and recent levels of circulating anti-double-stranded DNA. Past use of corticosteroids (in the absence of current use) was not associated with CVE rates. However, persons currently using 20 mg/day or more of corticosteroids had a substantial increase in risk even after adjustment for disease activity. Thus, consistent with findings in several recent publications among cohorts with other diseases, current use of corticosteroids was associated with an increased risk of CVEs. These results suggest a short-term impact of corticosteroids on CVE risk. PMID:23024137

  9. Leukocyte Activation in Obese Patients

    PubMed Central

    Minervino, Daniele; Gumiero, Daniela; Nicolazzi, Maria Anna; Carnicelli, Annamaria; Fuorlo, Mariella; Guidone, Caterina; Di Gennaro, Leonardo; Fattorossi, Andrea; Mingrone, Geltrude; Landolfi, Raffaele

    2015-01-01

    Abstract The rising prevalence of obesity is a major global health problem. In severe obesity, bariatric surgery (BS) allows to obtain a significant weight loss and comorbidities improvement, among them one of the factors is the thrombotic risk. In this observational study, we measured indices of leukocyte activation in severely obese patients as markers of increased thrombotic risk in relation with serum markers of inflammation before and after BS. Frequency of polymorphonuclear neutrophil-platelet (PLT) and monocyte (MONO)-PLT aggregates as well as of tissue factor (TF) expressing MONOs was measured in the peripheral blood of 58 consecutive obese patients and 30 healthy controls. In 31 of the 58 obese patients, data obtained at the enrollment were compared with those obtained at 3, 6, and 12 months after BS. Compared with healthy controls, obese patients showed a higher frequency of polymorphonuclear leukocyte (PMNL)-PLT aggregates (7.47 ± 2.45 [6.82–8.11]% vs 5.85 ± 1.89 [5.14–6.55]%, P = 0.001), MONO-PLT aggregates (12.31 ± 7.33 [10.38–14.24]% vs 8.14 ± 2.22 [7.31–8.97]%, P < 0.001), and TF expressing MONOs (4.01 ± 2.11 [3.45–4.56]% vs 2.64 ± 1.65 [2.02–3.25]%, P = 0.002). PMNL-PLT and MONO-PLT aggregate frequency was positively correlated with TF expressing MONOs (R2 = 0.260, P = 0.049 and R2 = 0.318, P = 0.015, respectively). BS was performed in 31 patients and induced a significant reduction of the body mass index, and waist and hip circumferences. These effects were associated with a significant decrease of PMNL-PLT aggregates at 12 months (7.58 ± 2.27 [6.75–8.42]% vs 4.47 ± 1.11 [3.93–5.01]%, P < 0.001), and a reduction of TF expressing MONOs at 6 (3.82 ± 2.04 [3.07–4.57]% vs 1.60 ± 1.69 [0.30–2.90]%, P = 0.008) and 12 months (3.82 ± 2.04 [3.07–4.57]% vs 1.71 ± 0.54 [1.45–1.97]%, P = 0.001) after BS. These data suggest that leukocyte

  10. Flare, Persistently Active Disease, and Serologically Active Clinically Quiescent Disease in Systemic Lupus Erythematosus: A 2-Year Follow-Up Study

    PubMed Central

    Conti, Fabrizio; Ceccarelli, Fulvia; Perricone, Carlo; Miranda, Francesca; Truglia, Simona; Massaro, Laura; Pacucci, Viviana Antonella; Conti, Virginia; Bartosiewicz, Izabella; Spinelli, Francesca Romana; Alessandri, Cristiano; Valesini, Guido

    2012-01-01

    Objective Several indices have been proposed to assess disease activity in patients with Systemic Lupus Erythematosus (SLE). Recent studies have showed a prevalence of flare between 28–35.3%, persistently active disease (PAD) between 46%–52% and serologically active clinically quiescent (SACQ) disease ranging from 6 to 15%. Our goal was to evaluate the flare, PAD and SACQ rate incidence in a cohort of SLE patients over a 2-year follow-up. Methods We evaluated 394 SLE patients. Flare was defined as an increase in SLEDAI-2K score of ≥4 from the previous visit; PAD was defined as a SLEDAI-2K score of ≥4, on >2 consecutive visits; SACQ was defined as at least a 2-year period without clinical activity and with persistent serologic activity. Results Among the 95 patients eligible for the analysis in 2009, 7 (7.3%) had ≥1 flare episode, whereas 9 (9.4%) had PAD. Similarly, among the 118 patients selected for the analysis in 2010, 6 (5%) had ≥1 flare episode, whereas 16 (13.5%) had PAD. Only 1/45 patient (2.2%) showed SACQ during the follow-up. Conclusion We showed a low incidence of flare, PAD and SACQ in Italian SLE patients compared with previous studies which could be partly explained by ethnic differences. PMID:23029327

  11. Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress through Regulation of CHOP and JNK in Bone Marrow Mesenchymal Stem Cells from Patients with Systemic Lupus Erythematosus.

    PubMed

    Guo, Genkai; Meng, Yan; Tan, Wei; Xia, Yunfei; Cheng, Chun; Chen, Xiaolan; Gu, Zhifeng

    2015-01-01

    Previous studies indicated that bone marrow mesenchymal stem cells (BM-MSCs) from patients with systemic lupus erythematosus (SLE) exhibited the phenomenon of apoptosis. In this study, we aimed to investigate whether apoptosis of BM-MSCs from SLE patients were dysregulated. In this paper, endoplasmic reticulum stress (ERS) was evidenced by increased expression of phosphorylated protein kinase RNA-like ER kinase (PERK) and inositol-requiring protein-1 (IRE-1). We also found the activation of downstream target eukaryotic translation initiator factor 2α (eIF 2α) and CCAAT/enhancer-binding protein- (C/EBP-) homologous protein (CHOP) in BM-MSCs from SLE patients. Interestingly, we discovered that 4-phenylbutyric acid (4-PBA), a selective inhibitor of ERS, blocked the apoptosis of BM-MSCs from SLE patients and alleviated the level of Jun N-terminal kinase1/2 (JNK1/2) and CHOP. Furthermore, blockage of PERK signaling expression by siRNA not only significantly reduced the expression of CHOP, but also activated the anti-apoptotic regulator B-cell lymphoma-2 (Bcl-2). Blockage of IRE-1 or JNK1/2 by siRNA resulted in the decreased expression of JNK1/2 and proapoptosis protein Bcl-2 associated protein X (BAX). These results implicated that ERS-mediated apoptosis was a critical determinant of BM-MSCs from SLE patients. PMID:26090483

  12. Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease.

    PubMed

    Wilbe, Maria; Kozyrev, Sergey V; Farias, Fabiana H G; Bremer, Hanna D; Hedlund, Anna; Pielberg, Gerli R; Seppälä, Eija H; Gustafson, Ulla; Lohi, Hannes; Carlborg, Örjan; Andersson, Göran; Hansson-Hamlin, Helene; Lindblad-Toh, Kerstin

    2015-06-01

    The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAMTOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans. PMID:26057447

  13. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

    PubMed

    Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

    2015-08-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. PMID:25926055

  14. Joint involvement in patients affected by systemic lupus erythematosus: application of the swollen to tender joint count ratio.

    PubMed

    Cipriano, E; Ceccarelli, F; Massaro, L; Spinelli, F R; Alessandri, C; Perricone, C; Valesini, G; Conti, F

    2015-01-01

    Joint involvement is a common manifestation in systemic lupus erythematosus (SLE). According to the SLE disease activity index 2000 (SLEDAI-2K), joint involvement is present in case of ≥2 joints with pain and signs of inflammation. However this definition could fail to catch all the various features of joint involvement. Alternatively the Swollen to Tender joint Ratio (STR) could be used. This new index, which was originally proposed for rheumatoid arthritis (RA) patients, is based on the count of 28 swollen and tender joints. Our study is, therefore, aimed to assess joint involvement in a SLE cohort using the STR. SLE patients with joint symptoms (≥1 tender joint) were enrolled over a period of one month. Disease activity was assessed by SLEDAI-2K. We performed the swollen and tender joint count (0-28) and calculated the STR. Depending on the STR, SLE patients were grouped into three categories of disease activity: low (STR1.0). We also calculated the disease activity score based on a 28-joint count and the erythrocyte sedimentation rate (DAS28-ESR). We enrolled 100 SLE patients [F/M 95/5, mean±standard deviation (SD) age 46.3±10.6 years, mean±SD disease duration 147.1±103.8 months]. The median of tender and swollen joints was 4 (IQR 7) and 1 (IQR 2.5), respectively. The median STR value was 0.03 (IQR 0.6). According to the STR, disease activity was low in 70 patients, moderate in 23 and high in 7. A significant correlation was identified between STR values and DAS28 (r=0.33, p=0.001). The present study suggests a correlation between STR and DAS28, allowing an easier and faster assessment of joint involvement with the former index. PMID:26492964

  15. Rhupus arthropathy as the presenting manifestation in Juvenile SLE: a case report

    PubMed Central

    Unsal, Erbil; Arlı, Ayse Ozgun; Akman, Hakkı

    2007-01-01

    An 8.5-year-old girl was referred with swelling of both knees lasting for two years. ANA was found as negative. She was diagnosed as oligoarticular JIA. After two years of follow-up, thrombocytopenia was detected during routine screening. Her ANA and anti ds-DNA antibodies also became positive, with low levels of C3 and C4. She was diagnosed as Juvenile SLE, meeting the criteria cytopenia, positive immunoserology (anti dsDNA), positive ANA test, and four years of ongoing chronic arthritis, so called as "rhupus arthropathy". We should be aware of the several initial incomplete presentations of lupus in children. We should be careful in monitoring the serious manifestations of the disease in juvenile lupus patients with rhupus arthropathy, and consider the poor response to standard disease modifying agents. PMID:17550633

  16. IgG and IgM autoantibody differences in discoid and systemic lupus patients.

    PubMed

    Chong, Benjamin F; Tseng, Lin-chiang; Lee, Thomas; Vasquez, Rebecca; Li, Quan Z; Zhang, Song; Karp, David R; Olsen, Nancy J; Mohan, Chandra

    2012-12-01

    Systemic lupus erythematosus (SLE) patients with discoid lupus erythematosus (DLE) were reported to have milder disease. To test this observation, we used sandwich arrays containing 98 autoantigens to compare autoantibody profiles of SLE subjects without DLE (DLE-SLE+) (N=9), SLE subjects with DLE (DLE+SLE+) (N=10), DLE subjects without SLE (DLE+SLE-) (N=11), and healthy controls (N=11). We validated differentially expressed autoantibodies using immunoassays in DLE-SLE+ (N=18), DLE+SLE+ (N=17), DLE+SLE- (N=23), and healthy subjects (N=22). Arrays showed 15 IgG autoantibodies (10 against nuclear antigens) and 4 IgM autoantibodies that were differentially expressed (q-value<0.05). DLE-SLE+ subjects had higher IgG autoantibodies against double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), double-stranded RNA (dsRNA), histone H2A and H2B, and SS-A (52 kDa) compared with all other groups including DLE+SLE+ subjects (P<0.05). Immunoassays measuring anti-dsDNA, -ssDNA, and -SS-A (52 kDa) IgG autoantibodies showed similar trends (P<0.05). Healthy and DLE+SLE- subjects expressed higher IgM autoantibodies against alpha beta crystallin, lipopolysaccharide, heat-shock cognate 70, and desmoglein-3 compared with DLE+SLE+ and DLE-SLE+ subjects. IgG:IgM ratios of autoantibodies against nuclear antigens progressively rose from healthy to DLE-SLE+ subjects. In conclusion, lower IgG autoantibodies against nuclear antigens in DLE+SLE+ versus DLE-SLE+ subjects suggest that DLE indicates lower disease severity. Higher IgM autoantibodies against selected antigens in healthy and DLE+SLE- subjects may be nonpathogenic. PMID:22763789

  17. Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry VI: Effect of Cigarette Smoking on the Clinical Phenotype of Chinese Patients with Systemic Lupus Erythematosus

    PubMed Central

    Zeng, Qingyu; Xu, Jianhua; Jiang, Lindi; Gong, Lu; Wu, Fengqi; Gu, Jieruo; Tao, Yi; Chen, Jinwei; Zhao, Jiuliang; Li, Mengtao; Zhao, Yan; Zeng, Xiaofeng

    2015-01-01

    Objectives Our study aimed to investigate the effect of cigarette smoking on the clinical phenotype of patients registered in the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research (CSTAR) group registry database, the first online registry of Chinese patients with SLE. Methods A prospective cross-sectional study of Chinese SLE patients was conducted using the CSTAR. Our case-control analysis was performed on age- and gender-matched subjects to explore the potential effect of cigarette smoking on the clinical manifestation of SLE. Results Smokers comprised 8.9% (65/730) of patients, and the ratio of females/males was 19/46. Thirty-nine patients were current smokers, and 26 were ex-smokers. Data showed significant differences between smokers and nonsmokers in the following areas: nephropathy (58.5% vs. 39.2%; p = 0.003), microscopic hematuria (30.8% vs. 19.1%; p = 0.025), proteinuria (53.8% vs. 34.4%; p = 0.002), and SLE Disease Activity Index(DAI) scores (12.38±8.95 vs. 9.83±6.81; p = 0.028). After adjusting for age and gender, significant differences between smokers and nonsmokers were found with photosensitivity (35.9% vs. 18%; p = 0.006), nephropathy (59.4% vs. 39.8%; p = 0.011), and proteinuria (54.7% vs. 35.2%). Although smokers tended to have greater disease severity compared with nonsmokers (SLEDAI scores: 12.58±8.89 vs.10.5±7.09), the difference was not significant (p = 0.081). Conclusions Cigarette smoking triggers the development and exacerbation of SLE, especially with respect to renal involvement. Chinese smokers with SLE should be advised to discontinue cigarette use. PMID:26280671

  18. Immunochemical studies on HNE-modified HSA: Anti-HNE-HSA antibodies as a probe for HNE damaged albumin in SLE.

    PubMed

    Khan, Farzana; Moinuddin; Mir, Abdul Rouf; Islam, Sidra; Alam, Khursheed; Ali, Asif

    2016-05-01

    Non-enzymatic lipid peroxidation of cellular membranes occurs during periods of sustained oxidative stress. 4-Hydroxynonenal (HNE), the most reactive lipid peroxidation product, is capable of modifying and/or cross-linking proteins leading to impaired physiological functions. The formation of protein adducts produce structural modifications which generate neo-antigens and induce auto-antibodies. Enhanced oxidative stress and accumulation of HNE-modified proteins are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. This study has probed the role of lipid peroxidation derived aldehydes in SLE. We report the structural perturbations in human serum albumin (HSA) upon modification with HNE and the consequential enhanced immunogenicity. The induced antibodies were found to be highly specific for the immunogen and exhibited cross-reactivity with HNE-modified epitopes on proteins, amino acids and nucleic acid. The experimentally induced anti-HNE-HSA antibodies appreciably recognized HNE modified epitopes on the HSA obtained from SLE patients. These antibodies, therefore, form a good immunochemical probe to detect such damages in lupus patients. Possible role of anti-HNE-HSA antibodies as a marker for detection/progression of SLE has been discussed. PMID:26800898

  19. Perceptions of racism in healthcare among patients with systemic lupus erythematosus: a cross-sectional study

    PubMed Central

    Vina, Ernest R; Hausmann, Leslie R M; Utset, Tammy O; Masi, Christopher M; Liang, Kimberly P; Kwoh, C Kent

    2015-01-01

    Background Racial disparities in the clinical outcomes of systemic lupus erythematosus (SLE) exist. Perceived racial discrimination may contribute to disparities in health. Objectives To determine if perceived racism in healthcare differs by race among patients with SLE and to evaluate its contribution to racial disparities in SLE-related outcomes. Methods 163 African–American (AA) and 180 white (WH) patients with SLE were enrolled. Structured interviews and chart reviews were done to determine perceptions of racism, SLE-related outcomes (Systemic Lupus International Collaborating Clinics (SLICC) Damage Index, SLE Disease Activity, Center for Epidemiologic Studies-Depression (CES-D)), and other variables that may affect perceptions of racism. Serial hierarchical multivariable logistic regression models were conducted. Race-stratified analyses were also performed. Results 56.0% of AA patients compared with 32.8% of WH patients had high perceptions of discrimination in healthcare (p<0.001). This difference remained (OR 4.75 (95% CI 2.41 to 8.68)) after adjustment for background, identity and healthcare experiences. Female gender (p=0.012) and lower trust in physicians (p<0.001) were also associated with high perceived racism. The odds of having greater disease damage (SLICC damage index ≥2) were higher in AA patients than in WH patients (crude OR 1.55 (95% CI 1.01 to 2.38)). The odds of having moderate to severe depression (CES-D ≥17) were also higher in AA patients than in WH patients (crude OR 1.94 (95% CI 1.26 to 2.98)). When adjusted for sociodemographic and clinical characteristics, racial disparities in disease damage and depression were no longer significant. Among AA patients, higher perceived racism was associated with having moderate to severe depression (adjusted OR 1.23 (95% CI 1.05 to 1.43)) even after adjusting for sociodemographic and clinical variables. Conclusions Perceptions of racism in healthcare were more common in AA patients than in WH

  20. Increased caspase-3 expression and activity contribute to reduced CD3zeta expression in systemic lupus erythematosus T cells.

    PubMed

    Krishnan, Sandeep; Kiang, Juliann G; Fisher, Carolyn U; Nambiar, Madhusoodana P; Nguyen, Hang T; Kyttaris, Vasileios C; Chowdhury, Bhabadeb; Rus, Violeta; Tsokos, George C

    2005-09-01

    T cells isolated from patients with systemic lupus erythematosus (SLE) express low levels of CD3zeta-chain, a critical molecule involved in TCR-mediated signaling, but the involved mechanisms are not fully understood. In this study we examined caspase-3 as a candidate for cleaving CD3zeta in SLE T cells. We demonstrate that SLE T cells display increased expression and activity of caspase-3. Treatment of SLE T cells with the caspase-3 inhibitor Z-Asp-Glu-Val-Asp-FMK reduced proteolysis of CD3zeta and enhanced its expression. In addition, Z-Asp-Glu-Val-Asp-FMK treatment increased the association of CD3zeta with lipid rafts and simultaneously reversed the abnormal lipid raft preclustering, heightened TCR-induced calcium responses, and reduced the expression of FcRgamma-chain exclusively in SLE T cells. We conclude that caspase-3 inhibitors can normalize SLE T cell function by limiting the excessive digestion of CD3zeta-chain and suggest that such molecules can be considered in the treatment of this disease. PMID:16116236

  1. Mitochondrial Hyperpolarization and ATP Depletion in Patients With Systemic Lupus Erythematosus

    PubMed Central

    Gergely, Peter; Grossman, Craig; Niland, Brian; Puskas, Ferenc; Neupane, Hom; Allam, Fatme; Banki, Katalin; Phillips, Paul E.; Perl, Andras

    2014-01-01

    Objective Peripheral blood lymphocytes (PBLs) from systemic lupus erythematosus (SLE) patients exhibit increased spontaneous and diminished activation-induced apoptosis. We tested the hypothesis that key biochemical checkpoints, the mitochondrial transmembrane potential (ΔΨm) and production of reactive oxygen intermediates (ROIs), mediate the imbalance of apoptosis in SLE. Methods We assessed the ΔΨm with potentiometric dyes, measured ROI production with oxidation-sensitive fluorochromes, and monitored cell death by annexin V and propidium iodide staining of lymphocytes, using flow cytometry. Intracellular glutathione levels were measured by high-performance liquid chromatography, while ATP and ADP levels were assessed by the luciferin–luciferase assay. Results Both ΔΨm and ROI production were elevated in the 25 SLE patients compared with the 25 healthy subjects and the 10 rheumatoid arthritis patients. Intracellular glutathione contents were diminished, suggesting increased utilization of reducing equivalents in SLE. H2O2, a precursor of ROIs, increased ΔΨm and caused apoptosis in normal PBLs. In contrast, H2O2-induced apoptosis and ΔΨm elevation were diminished, particularly in T cells, and the rate of necrotic cell death was increased in patients with SLE. The intracellular ATP content and the ATP:ADP ratio were reduced and correlated with the ΔΨm elevation in lupus. CD3:CD28 costimulation led to transient elevation of the ΔΨm, followed by ATP depletion, and sensitization of normal PBLs to H2O2-induced necrosis. Depletion of ATP by oligomycin, an inhibitor of F0F1–ATPase, had similar effects. Conclusion T cell activation and apoptosis are mediated by ΔΨm elevation and increased ROI production. Mitochondrial hyperpolarization and the resultant ATP depletion sensitize T cells for necrosis, which may significantly contribute to inflammation in patients with SLE. PMID:11817589

  2. In vitro induction of IgG anti-DNA antibody from high density B cells of systemic lupus erythematosus patients by an HLA DR-restricted T cell clone.

    PubMed Central

    Murakami, M; Kumagai, S; Sugita, M; Iwai, K; Imura, H

    1992-01-01

    An HLA-DR restricted T cell clone (26G11) which recognized a lymphoid cell-derived autoantigen associated with DR4 molecule was shown to induce not only autologous but also allogenic DR4+ B cells to produce large amounts of antibodies of the IgG and IgM classes. Using the helper activity of this clone, we investigated the mechanism of anti-DNA antibody production in DR-matched patients with systemic lupus erythematosus (SLE). When cultured with 26G11 cells, B cells from DR-matched normal control subjects produced large amounts of IgM anti-DNA antibody, but did not produce IgG anti-DNA antibody which is thought to have a pathological role in SLE. In contrast, B cells from DR-matched patients with active SLE spontaneously produced a fairly large amount of IgG anti-DNA antibody, and the production was augmented by the T cell clone. Little IgG anti-DNA antibody was produced by the B cells of patients with inactive SLE in either the presence or absence of T cell clone. We next fractionated B cells into low density B (LD-B) and high density B (HD-B) cells by centrifugation on discontinuous Percoll density gradients. IgG anti-DNA antibody was spontaneously produced by LD-B cells of active SLE patients but not by those either of inactive SLE patients or normal controls. On the other hand, although IgG anti-DNA antibody was not spontaneously produced by the HD-B cells of both active and inactive SLE patients, it could easily be induced by their culture with the T cell clone. Our results clearly show the existence of IgG anti-DNA antibody-producing B cells in the peripheral blood of SLE patients irrespective of their disease activity and suggest that autoreactive T cells may play a pathogenic role in SLE through the induction of autoantibody production. PMID:1424281

  3. STS-1 promotes IFN-α induced autophagy by activating the JAK1-STAT1 signaling pathway in B cells.

    PubMed

    Dong, Guanjun; You, Ming; Fan, Hongye; Ding, Liang; Sun, Lingyun; Hou, Yayi

    2015-08-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overexpression of IFN-α. IFN-α induces autophagy via the JAK1-STAT1 signaling pathway, contributing to the pathogenesis of SLE. Recent studies reported that B cells from patients with SLE and NZB/W F1 mice had enhanced autophagy activity; however, the mechanism still remains unknown. Here, we show that the protein tyrosine phosphatase STS-1 (suppressor of T-cell receptor signaling 1) was significantly overexpressed in B cells from patients with SLE and MRL/lpr mice. Notably, STS-1 promoted IFN-α-induced autophagy in B cells by enhancing the JAK1-STAT1 signaling activation. STS-1 inhibited the phosphorylation of the E3 ubiquitin protein ligase c-cbl, and subsequently promoted IFN-α-induced phosphorylation of tyrosine kinase 2, leading to JAK1-STAT1 signaling activation. Furthermore, STAT1 and JAK1 inhibitors blocked the IFN-α-induced autophagy promoted by STS-1, indicating that STS-1 promotes IFN-α-induced autophagy via the JAK1-STAT1 signaling. Our results demonstrate the importance of STS-1 in regulating IFN-α-induced autophagy in B cells, and this could be used as a therapeutic approach to treat SLE. PMID:25959715

  4. Patient Activation: Public Libraries and Health Literacy

    ERIC Educational Resources Information Center

    Malachowski, Margot

    2011-01-01

    Patient activation is a new term for a perennial problem. People know what they need to do for their health: exercise, eat right, and get enough rest--but how are they motivated to actually do these things? This is what patient activation is. From this author's vantage point as a medical librarian, public libraries are well-placed to be part of…

  5. A prospective multicentre study of mycophenolate mofetil combined with prednisolone as induction therapy in 213 patients with active lupus nephritis.

    PubMed

    F, Lu; Y, Tu; X, Peng; L, Wang; H, Wang; Z, Sun; H, Zheng; Z, Hu

    2008-07-01

    Mycophenolate mofetil (MMF) with prednisolone has been associated with high remission rates when used as induction treatment for lupus nephritis. This prospective, multicentre, cohort study investigates the efficacy and safety of this regimen over 24 weeks in 213 Chinese patients with active lupus nephritis (Classes III, IV, V or combination). Baseline activity index (AI) was 6.91+/-3.33 and chronicity index (CI) was 1.9+/-1.2. The remission rate was 82.6% at 24 weeks (complete remission, 34.3%; partial remission, 48.4%). There were significant (P<0.01) improvements in kidney function shown by reductions in proteinuria, serum albumin, serum creatinine and creatinine clearance, as well as in systemic lupus erythematosus disease activity index (SLEDAI) scores. Independent risk factors influencing remission were pathological classification (including Class V and III or Class V and IV nephritis) and elevated serum creatinine at baseline (OR 2.967, 95% CI: 1.479-6.332, P=0.001 and OR 1.007, 95% CI: 1.002-1.011, P=0.001, respectively). Patients with concomitant membranous features on biopsy had a lower remission rate than those with Class III and IV nephritis (66.7% vs 87.3%, P=0.002). Renal biopsy was repeated in 25 patients following treatment. There was a transition to less severe pathological morphologies in majority of subjects. Infections were monitored throughout treatment: eight patients (3.8%) experienced bacterial infections, whereas herpes zoster occurred in seven patients. Nine patients (4.2%) suffered from gastrointestinal upset, which resolved without discontinuation of MMF. One patient became leucopenic, whereas another died from active disease unrelated to kidney symptoms. MMF combined with prednisolone is an effective and well-tolerated induction treatment for patients with active lupus nephritis and for controlling SLE systemic activity. PMID:18625634

  6. Characterization of warm-reactive IgG anti-lymphocyte antibodies in systemic lupus erythematosus. Relative specificity for mitogen-activated T cells and their soluble products.

    PubMed

    Litvin, D A; Cohen, P L; Winfield, J B

    1983-01-01

    In addition to previously described cold-reactive IgM anti-lymphocyte antibodies maximally cytotoxic for resting cells at 15 degrees C, sera from patients with systemic lupus erythematosus (SLE) were found to contain a new type of antibody preferentially reactive at physiologic temperatures with mitogen-activated lymphocytes. This antibody lacked specificity for unstimulated lymphocytes, and was shown to be of the IgG class both by indirect immunofluorescence and in immunochemical experiments. Certain SLE sera also contained IgG antibodies with the capacity to develop plaques with mitogen-activated T lymphocyte preparations used in a reverse hemolytic plaque assay, indicating reactivity with products released by activated cells. The elimination of the ability of SLE sera to develop plaques after absorption with viable mitogen-stimulated lymphocytes, but not with resting cells, suggested that these antibodies were directed toward activation "neoantigen(s)" shed from the cell surface membrane. Surface membrane phenotype analyses performed by using a variety of monoclonal antibody reagents indicated that the plaque-forming cells (PFC) detected with SLE sera were activated T lymphocytes not restricted to single OKT4+, OKT8+, or Ia antigen+ subpopulations. Essentially all PFC expressed transferrin receptors. The present data raise the possibility that certain of the interesting effects of anti-lymphocyte antibodies on immunologic function in SLE may be mediated by interactions of these new type(s) of antibodies with activated lymphocytes or their products, rather than through blocking or depletion effects on resting precursor cells. PMID:6600174

  7. Characterization of in vivo mutated T cell clones from patients with systemic lupus erythematosus.

    PubMed

    Theocharis, S; Sfikakis, P P; Lipnick, R N; Klipple, G L; Steinberg, A D; Tsokos, G C

    1995-02-01

    Patients with systemic lupus erythematosus (SLE) have increased percentages of activated T cells and increased numbers of cells with mutations in their hypoxanthineguanine phosphoribosyltransferase (hprt) gene, as judged by growth in the presence of 6-thioguanine. To study the relevance of these mutant T cells to disease pathogenesis, we have assessed the phenotype and functional capabilities of such cells from 21 patients with SLE who never had received cytotoxic drugs. The frequency of T cells with mutations in hprt in the blood of these patients ranged from normal to 25 times normal (mean +/- SEM [21.1 +/- 6.1] x 10(-6) versus [4.8 +/- 0.8] x 10(-6), in 15 age-matched normal individuals, P < 0.001) and correlated significantly with disease duration. CD4+ and CD8+ phenotypes were comparable among mutated and nonmutated clones from both patients and normals. Although the frequency of CD3+CD4-CD8- cells was low, it was increased among SLE-derived T cells (mutated and wild-type) compared with clones derived from normals (5% for SLE vs 1% for normals). A substantial percentage of all clones were able to help autologous B cells to produce anti-ssDNA, 11 of 68 (16%) selected clones and 3 of 28 (11%) nonselected clones. Help for autoantibody production was confined to CD4+ SLE-derived T cell clones. It could be blocked using an anti-HLA-DR mAb, suggesting that classical cognate help was operative. This represents the first estimate of the frequency of T cells able to drive autoantibody production in SLE. PMID:7828367

  8. Comparative Transcriptional Profiling of 3 Murine Models of SLE Nephritis Reveals Both Unique and Shared Regulatory Networks

    PubMed Central

    Zhang, Weijia; Kretzler, Matthias; Davidson, Anne

    2013-01-01

    Objective To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease. Methods Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR. Results 955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss. Conclusions These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune–mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis. PMID:24167575

  9. Cutting Edge: Autoimmune Disease Risk Variant of STAT4 Confers Increased Sensitivity to IFN-α in Lupus Patients In Vivo1

    PubMed Central

    Kariuki, Silvia N.; Kirou, Kyriakos A.; MacDermott, Emma J.; Barillas-Arias, Lilliana; Crow, Mary K.; Niewold, Timothy B.

    2009-01-01

    Increased IFN-α signaling is a primary pathogenic factor in systemic lupus erythematosus (SLE). STAT4 is a transcription factor that is activated by IFN-α signaling, and genetic variation of STAT4 has been associated with risk of SLE and rheumatoid arthritis. We measured serum IFN-α activity and simultaneous IFN-α-induced gene expression in PBMC in a large SLE cohort. The risk variant of STAT4 (T allele; rs7574865) was simultaneously associated with both lower serum IFN-α activity and greater IFN-α-induced gene expression in PBMC in SLE patients in vivo. Regression analyses confirmed that the risk allele of STAT4 was associated with increased sensitivity to IFN-α signaling. The IFN regulatory factor 5 SLE risk genotype was associated with higher serum IFN-α activity; however, STAT4 showed dominant influence on the sensitivity of PBMC to serum IFN-α. These data provide biologic relevance for the risk variant of STAT4 in the IFN-α pathway in vivo. PMID:19109131

  10. Diet-induced systemic lupus erythematosus (SLE) in primates.

    PubMed

    Bardana, E J; Malinow, M R; Houghton, D C; McNulty, W P; Wuepper, K D; Parker, F; Pirofsky, B

    1982-05-01

    Ten adult, female cynomolgus macaques were randomly assigned to two equal groups: (1) semipurified diet (SPD); and (2) SPD with 45% ground alfalfa seed (AS). Both groups were studied at monthly intervals after 5 mo on their respective diets. Control animals had a mean hematocrit (Hct) of 43 +/- 2%, negative antiglobulin (AG), antinuclear antibody (ANA) and LE cell tests. Mean values for C3 and C4 were 309 +/- 47 mg/dl and 35 +/- 7 mg/dl, respectively. Mean serum binding to radiolabeled double stranded deoxyribonucleic acid (dsDNA) was 1.9 +/- 0.2%. Three of five animals fed AS developed signs of an SLE-like illness characterized by AG-positive anemia (lowest Hct 30%), positive ANA (highest titer greater than 1:15, 360; rim pattern) and elevated anti-dsDNA binding (highest 96%) with variable degrees of hypocomplementemia. One animal had granular deposition of immunoglobulin and complement at the dermal-epidermal junction of clinically normal skin the presence of immune complex-induced glomerulonephritis. PMID:6178289

  11. Histone H2AX phosphorylation as a measure of DNA double-strand breaks and a marker of environmental stress and disease activity in lupus

    PubMed Central

    Namas, Rajaie; Renauer, Paul; Ognenovski, Mikhail; Tsou, Pei-Suen; Sawalha, Amr H

    2016-01-01

    Objective Defective or inefficient DNA double-strand break (DSB) repair results in failure to preserve genomic integrity leading to apoptotic cell death, a hallmark of systemic lupus erythematosus (SLE). Compelling evidence linked environmental factors that increase oxidative stress with SLE risk and the formation of DSBs. In this study, we sought to further explore genotoxic stress sensitivity in SLE by investigating DSB accumulation as a marker linking the effect of environmental stressors and the chromatin microenvironment. Methods DSBs were quantified in peripheral blood mononuclear cell subsets from patients with SLE, healthy controls, and patients with rheumatoid arthritis (RA) by measuring phosphorylated H2AX (phospho-H2AX) levels with flow cytometry. Phospho-H2AX levels were assessed in G0/G1, S and G2 cell-cycle phases using propidium iodide staining, and after oxidative stress using 0.5 µM hydrogen peroxide exposure for 0, 2, 5, 10, 30 and 60 min. Results DSB levels were significantly increased in CD4+ T cells, CD8+ T cells and monocytes in SLE compared with healthy controls (p=2.16×10−4, 1.68×10−3 and 4.74×10−3, respectively) and RA (p=1.05×10−3, 1.78×10−3 and 2.43×10−2, respectively). This increase in DSBs in SLE was independent of the cell-cycle phase, and correlated with disease activity. In CD4+ T cells, CD8+ T cells and monocytes, oxidative stress exposure induced significantly higher DSB accumulation in SLE compared with healthy controls (60 min; p=1.64×10−6, 8.11×10−7 and 2.04×10−3, respectively). Conclusions Our data indicate that SLE T cells and monocytes have increased baseline DSB levels and an increased sensitivity to acquiring DSBs in response to oxidative stress. Although the mechanism underlying DSB sensitivity in SLE requires further investigation, accumulation of DSB may serve a biomarker for disease activity in SLE and help explain increased apoptotic cell accumulation in this disease. PMID:27158526

  12. Adrenal function in patients with active tuberculosis.

    PubMed Central

    Barnes, D J; Naraqi, S; Temu, P; Turtle, J R

    1989-01-01

    Although tuberculosis is a recognised cause of adrenal insufficiency, little is known about adrenal function in patients with active tuberculosis. Ninety Melanesian adults with active tuberculosis (30 pulmonary, 30 miliary, 30 extrapulmonary) had adrenal function assessed prospectively before and three to four weeks after starting antituberculous chemotherapy. Basal serum cortisol concentrations were normal in 55 (61%) and raised in 35 (39%) of the subjects. No patient had a low basal cortisol concentration. After Synacthen stimulation, cortisol responses were normal in 81 (92%) of the patients and subnormal in seven (8%). After antituberculous chemotherapy the response to Synacthen stimulation was normal in all but one patient. It is concluded that adrenal dysfunction is an uncommon problem in patients with active tuberculosis, and that, contrary to recent reports, antituberculous chemotherapy regimens that include rifampicin do not have an adverse effect on adrenal function. PMID:2763243

  13. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.

    PubMed

    Banchereau, Romain; Hong, Seunghee; Cantarel, Brandi; Baldwin, Nicole; Baisch, Jeanine; Edens, Michelle; Cepika, Alma-Martina; Acs, Peter; Turner, Jacob; Anguiano, Esperanza; Vinod, Parvathi; Kahn, Shaheen; Obermoser, Gerlinde; Blankenship, Derek; Wakeland, Edward; Nassi, Lorien; Gotte, Alisa; Punaro, Marilynn; Liu, Yong-Jun; Banchereau, Jacques; Rossello-Urgell, Jose; Wright, Tracey; Pascual, Virginia

    2016-04-21

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nucleic acids and highly diverse clinical manifestations. To assess its molecular heterogeneity, we longitudinally profiled the blood transcriptome of 158 pediatric patients. Using mixed models accounting for repeated measurements, demographics, treatment, disease activity (DA), and nephritis class, we confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of DA. We detected gradual enrichment of neutrophil transcripts during progression to active nephritis and distinct signatures in response to treatment in different nephritis subclasses. Importantly, personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials. This approach may improve trial design and implementation of tailored therapies in genetically and clinically complex autoimmune diseases. PAPERCLIP. PMID:27040498

  14. Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin

    PubMed Central

    Legorreta-Haquet, María Victoria; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Cervera-Castillo, Hernando; Zenteno-Galindo, Edgar; Barile-Fabris, Leonor; Burgos-Vargas, Rubén; Álvarez-Hernández, Everardo; Blanco-Favela, Francisco

    2016-01-01

    Abstract Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4+CD25hiCD127−/low cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment. PMID:26844452

  15. Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin.

    PubMed

    Legorreta-Haquet, María Victoria; Chávez-Rueda, Karina; Chávez-Sánchez, Luis; Cervera-Castillo, Hernando; Zenteno-Galindo, Edgar; Barile-Fabris, Leonor; Burgos-Vargas, Rubén; Álvarez-Hernández, Everardo; Blanco-Favela, Francisco

    2016-02-01

    Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4CD25CD127 cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment. PMID:26844452

  16. Serotonin content of platelets in inflammatory rheumatic diseases. Correlation with clinical activity.

    PubMed

    Zeller, J; Weissbarth, E; Baruth, B; Mielke, H; Deicher, H

    1983-04-01

    Significantly decreased platelet serotonin contents were measured in rheumatoid arthritis, systemic lupus erythematosus (SLE), progressive systemic sclerosis, and mixed connective tissue disease. An inverse relationship between platelet serotonin levels and clinical disease activity was observed in both rheumatoid arthritis and systemic lupus erythematosus. SLE patients with multiple organ involvement showed the lowest platelet serotonin values. No correlation was observed between platelet serotonin contents and nonsteroidal antiinflammatory drug treatment, presence of circulating platelet reactive IgG, or the amount of circulating immune complexes. The results are interpreted as indicating platelet release occurring in vivo during inflammatory episodes of the rheumatic disorders investigated. PMID:6838676

  17. Space Link Extension (SLE) Emulation for High-Throughput Network Communication

    NASA Technical Reports Server (NTRS)

    Murawski, Robert; Tchorowski, Nicole; Golden, Bert

    2014-01-01

    As the data rate requirements for space communications increases, signicant stressis placed not only on the wireless satellite communication links, but also on the groundnetworks which forward data from end-users to remote ground stations. These wide areanetwork (WAN) connections add delay and jitter to the end-to-end satellite communicationlink, eects which can have signicant impacts on the wireless communication link. It isimperative that any ground communication protocol can react to these eects such that theground network does not become a bottleneck in the communication path to the satellite.In this paper, we present our SCENIC Emulation Lab testbed which was developed to testthe CCSDS SLE protocol implementations proposed for use on future NASA communica-tion networks. Our results show that in the presence of realistic levels of network delay,high-throughput SLE communication links can experience signicant data rate throttling.Based on our observations, we present some insight into why this data throttling happens,and trace the probable issue back to non-optimal blocking communication which is sup-ported by the CCSDS SLE API recommended practices. These issues were presented aswell to the SLE implementation developers which, based on our reports, developed a newrelease for SLE which we show xes the SLE blocking issue and greatly improves the pro-tocol throughput. In this paper, we also discuss future developments for our end-to-endemulation lab and how these improvements can be used to develop and test future spacecommunication technologies.

  18. Space Link Extension (SLE) Emulation for High-Throughput Network Communication

    NASA Technical Reports Server (NTRS)

    Murawski, Robert W.; Tchorowski, Nicole; Golden, Bert

    2014-01-01

    As the data rate requirements for space communications increases, significant stress is placed not only on the wireless satellite communication links, but also on the ground networks which forward data from end-users to remote ground stations. These wide area network (WAN) connections add delay and jitter to the end-to-end satellite communication link, effects which can have significant impacts on the wireless communication link. It is imperative that any ground communication protocol can react to these effects such that the ground network does not become a bottleneck in the communication path to the satellite. In this paper, we present our SCENIC Emulation Lab testbed which was developed to test the CCSDS SLE protocol implementations proposed for use on future NASA communication networks. Our results show that in the presence of realistic levels of network delay, high-throughput SLE communication links can experience significant data rate throttling. Based on our observations, we present some insight into why this data throttling happens, and trace the probable issue back to non-optimal blocking communication which is sup-ported by the CCSDS SLE API recommended practices. These issues were presented as well to the SLE implementation developers which, based on our reports, developed a new release for SLE which we show fixes the SLE blocking issue and greatly improves the protocol throughput. In this paper, we also discuss future developments for our end-to-end emulation lab and how these improvements can be used to develop and test future space communication technologies.

  19. [Pseudocholinesterase activity in type 1 bipolar patients].

    PubMed

    Ezzaher, Asma; Haj Mouhamed, Dhouha; Mechri, Anwar; Neffati, Fadoua; Douki, Wahiba; Gaha, Lotfi; Najjar, Mohamed Fadhel

    2012-01-01

    This study aims to investigate the variation of pseudocholinesterase activity (BuChE) in bipolar patients and to explore its relation to the clinical and therapeutic characteristics of this disease. Our study included 105 patients with bipolar disorder and 100 control subjects aged 38.7 ± 12.2 and 36.4 ± 15.7 y, respectively. BuChE was determined by kinetic methods on Cobas Integra 400 plus™. Compared with controls, patients had a significantly higher pseudocholinesterase activity. Moreover, this increase was significantly associated (p = 0.001) with bipolar disorder with sensibility of 58% and specificity of 62% at threshold of 7392 IU/L. There was no significant change in pseudocholinesterase activity in relation to illness episodes and treatment, whereas the lowest values of this activity were seen in euthymic patients and those taking psychotics. Therefore, this activity is a real interest in the biological monitoring of patients as a risk factor for neurodegenerative diseases associated with bipolar disorder. But it would be most useful to evaluate their interest as a predictor of bipolar disorder in patients at risk. PMID:22294139

  20. Association of interleukin-10 promoter haplotypes with disease susceptibility and IL-10 levels in Mexican patients with systemic lupus erythematosus.

    PubMed

    Palafox-Sánchez, Claudia Azucena; Oregon-Romero, Edith; Salazar-Camarena, Diana Celeste; Valle, Yeminia Maribel; Machado-Contreras, Jesús René; Cruz, Alvaro; Orozco-López, Mariana; Orozco-Barocio, Gerardo; Vázquez-Del Mercado, Mónica; Muñoz-Valle, José Francisco

    2015-11-01

    Systemic lupus erythematosus (SLE) is the prototype autoimmune rheumatic disease. The etiology of this disease is incompletely understood; however, environmental factors and genetic predisposition are involved. Cytokine-mediated immunity plays a crucial role in the pathogenesis of SLE. We investigate the association of interleukin-10 (IL-10) promoter polymorphisms and their haplotypes in SLE patients from the western Mexico. One hundred and twenty-five SLE patients fulfilling the 1997 ACR criteria and 260 unrelated healthy subjects (HS), both Mexican mestizos, were genotyped for IL-10 -1082A>G, -819C>T, and -592C>A polymorphisms. Haplotypes were inferred using the expectation-maximization algorithm, then allele and haplotype distributions were compared between patients and HS, as well as patients with different clinical variables. We identified at -1082, -819, and -592 four predominant haplotypes ACC (43.70 % in patients vs 46.55 % in HS), ATA (21.45 vs 22.97 %), GCC (16.28 vs 14.21 %), and GTA (14.12 vs 14.12 %). The ATC haplotype was more frequent in SLE respect to HS, suggesting a risk effect (3.23 vs 1.05 %; OR 3.55, CI 1.14-11.11; p = 0.0293). SLE patient carriers of -592 CC genotype as well as the dominant model of inheritance showed higher sIL-10 respect to AA genotype, suggesting that -592 C allele is associated with increased production of the cytokine (p < 0.05). The ACC haplotype had higher IL-10 serum levels and higher values of Mexican version of the Systemic Lupus Erythematosus Disease Activity Index compared with the other haplotype carriers; however, no association was found regarding autoantibodies. Our data suggest that the IL-10 promoter haplotypes play an important role in the risk of developing SLE and influence the production of IL-10 in Mexican population. Nevertheless, further studies are required to analyze the expression of mRNA as well as to investigate the interacting epigenetic factors that could help to define the true contribution of

  1. Systemic lupus erythematosus and primary fibromyalgia can be distinguished by testing for cell-bound complement activation products

    PubMed Central

    Wallace, Daniel J; Silverman, Stuart L; Conklin, John; Barken, Derren; Dervieux, Thierry

    2016-01-01

    Objective We sought to establish the performance of cell-bound complement activation products (CB-CAPs) as a diagnostic tool to distinguish primary fibromyalgia (FM) from systemic lupus erythematosus (SLE). Methods A total of 75 SLE and 75 primary FM adult subjects who fulfilled appropriate classification criteria were enrolled prospectively. CB-CAPs (erythrocyte-C4d (EC4d) and B-lymphocyte-C4d (BC4d)) were determined by flow cytometry. Antinuclear antibodies (ANAs) were determined using indirect immunofluorescence while other autoantibodies were determined by solid-phase assays. The CB-CAPs in a multi-analyte assay with algorithm (MAAA) relied on two consecutive tiers of analysis that was reported as an overall positive or negative assessment. Test performance was assessed using sensitivity, specificity, positive and negative likelihood ratio (LR). Results ANAs yielded 80% positives for SLE and 33% positives for FM. High CB-CAP expression (EC4d >14 units or BC4d >60 units) was 43% sensitive and 96% specific for SLE. The CB-CAPs in MAAA assessment was evaluable in 138 of the 150 subjects enrolled (92%) and yielded 60% sensitivity (CI 95% 48% to 72%) for SLE with no FM patient testing positive (100% specificity). A positive test result was associated with a strong positive LR for SLE (>24, CI 95%; 6 to 102), while a negative test result was associated with a moderate negative LR (0.40; CI 95% 0.30 to 0.54). Conclusion Our data indicate that CB-CAPs in MAAA can distinguish FM from SLE. PMID:26870391

  2. B cells from patients with systemic lupus erythematosus display abnormal antigen receptor-mediated early signal transduction events.

    PubMed Central

    Liossis, S N; Kovacs, B; Dennis, G; Kammer, G M; Tsokos, G C

    1996-01-01

    To understand the molecular mechanisms that are responsible for the B cell overactivity that is observed in patients with SLE, we have conducted experiments in which the surface immunoglobulin (sIg)-mediated early cell signaling events were studied. The anti-sIgM-mediated free intracytoplasmic calcium ([Ca2+]i) responses were significantly higher in SLE B cells compared with responses of normal individuals and to those of patients with other systemic autoimmune rheumatic diseases. The anti-IgD mAb induced [Ca2+]i responses were also higher in lupus B cells than in controls. The magnitude of anti-sIgM-mediated Ca2+ release from intracellular stores was also increased in B cells from SLE patients compared with normal controls. The amount of inositol phosphate metabolites produced upon crosslinking of sIgM was slightly higher in patients with lupus than in normal controls, although the difference was not statistically significant. In contrast, the degree of anti-sIgM-induced protein tyrosine phosphorylation was obviously increased in lupus patients. Our study demonstrates clearly for the first time that SLE B cells exhibit aberrant early signal transduction events, including augmented calcium responses after crosslinking of the B cell receptor and increased antigen-receptor-mediated phosphorylation of protein tyrosine residues. Because the above abnormalities did not correlate with disease activity or treatment status, we propose that they may have pathogenic significance. PMID:8958217

  3. Physical activity in patients with anorexia nervosa.

    PubMed

    Achamrah, Najate; Coëffier, Moïse; Déchelotte, Pierre

    2016-05-01

    Anorexia nervosa (AN) is often associated with physical hyperactivity. Recent studies have established links between anorexia and hyperactivity, suggesting the existence of commonalities in neural pathways. How physical activity should be managed during the clinical care of patients with anorexia remains controversial. This review first focuses on the implication of hyperactivity in the pathophysiology of AN. Hyperactivity during refeeding of patients with AN has been associated with increased energy needs to achieve weight gain, poorer clinical outcome, longer hospitalization, and increased psychiatric comorbidity. This typically leads to the prescription of bed rest. However, current knowledge suggests that preserving some kind of physical activity during refeeding of patients with AN should be safe and beneficial for the restoration of body composition, the preservation of bone mineral density, and the management of mood and anxiety. In the absence of standardized guidelines, it is suggested here that physical activity during refeeding of patients with AN should be personalized according to the physical and mental status of each patient. More research is needed to assess whether programmed physical activity may be a beneficial part of the treatment of AN. PMID:27052638

  4. Prolidase activity in chronic plaque psoriasis patients

    PubMed Central

    Aksoy, Nurten; Ozgöztas, Orhan; Sezen, Hatice; Yesilova, Yavuz; Turan, Enver

    2015-01-01

    Introduction Psoriasis is a chronic, inflammatory, T-cell-mediated and hyperproliferative skin disease characterized by erythematous, squamous, sharply circumscribed and infiltrated plaques. The metabolisms of the collagen proteins undergo considerable changes due to the acceleration of their turnovers as a result of increased prolidase activity in psoriasis patients. Aim To determine the level of prolidase activity in psoriasis patients and evaluate its relationship with the oxidative system. Material and methods The serum prolidase enzyme activity, total antioxidant levels and total oxidant levels of 40 psoriasis patients and a control group including 47 healthy individuals were analyzed by using their serum samples, and their oxidative stress indices were calculated. Results The prolidase levels (p < 0.01), total oxidant levels (p < 0.01) and oxidative stress index levels (p < 0.001) of the patient group were higher than the corresponding parameters in the control group. The total antioxidant level was low (p < 0.01). Although a positive correlation was found between the prolidase and total antioxidant levels and the total oxidant level, no correlation was found between prolidase and the oxidative stress index. Conclusions It has been determined that the activity of the prolidase enzyme increases due to the increased collage turnover in psoriasis patients. Increased serum oxidant levels and oxidative stress indices values may play a role in the pathogenesis of psoriasis. PMID:26015776

  5. Evaluation of the P Wave Axis in Patients With Systemic Lupus Erythematosus

    PubMed Central

    Acar, Rezzan Deniz; Bulut, Mustafa; Acar, Şencan; Izci, Servet; Fidan, Serdar; Yesin, Mahmut; Efe, Suleyman Cagan

    2015-01-01

    Introduction: P wave axis is one of the most practical clinical tool for evaluation of cardiovascular disease. The aim of our study was to evaluate the P wave axis in electrocardiogram (ECG), left atrial function and association between the disease activity score in patients with systemic lupus erythematosus (SLE). Methods: Standard 12-lead surface ECGs were recorded by at a paper speed of 25 m/s and an amplifier gain of 10 mm/mV. The heart rate (HR), the duration of PR, QRS, QTd (dispersion), the axis of P wave were measured by ECG machine automatically. Results: The P wave axis was significantly increased in patients with SLE (49 ± 20 vs. 40 ± 18, P = 0.037) and the disease activity score was found positively correlated with P wave axis (r: 0.382, P = 0.011). The LA volume and the peak systolic strain of the left atrium (LA) were statistically different between the groups (P = 0.024 and P = 0.000). The parameters of the diastolic function; E/A and E/e’ were better in the control group than the patients with SLE (1.1 ± 0.3 vs. 1.3 ± 0.3, P = 0.041 and 6.6 ± 2.8 vs. 5.4 ± 1.4, P = 0.036, respectively). Conclusion: P wave axis was found significantly increased in patients with SLE and positively correlated with SELENA-SLEDAI score. As the risk score increases in patients with SLE, P wave axis changes which may predict the risk of all-cause and cardiovascular mortality. PMID:26702344

  6. Disease Activity and Damage are not Associated with Increased Levels of Fatigue in Systemic Lupus Erythematosus Patients from LUMINA LXVII, a Multiethnic Cohort

    PubMed Central

    Burgos, Paula I.; Alarcón, Graciela S.; McGwin, Gerald; Crews, Kendra Q.; Reveille, John D.; Vilá, Luis M.

    2009-01-01

    Objective To determine the factors associated with increased levels of fatigue over the course of the disease in systemic lupus erythematosus (SLE) patients from LUMINA (Lupus in Minorities: Nature versus Nurture), a longitudinal multiethnic cohort. Methods Patients with SLE (American College of Rheumatology revised and updated criteria), age ≥16 years, disease duration ≤ 5 years at entry into the cohort (T0), of Hispanic (Texan or Puerto Rican), African America or Caucasian ethnicity, were studied. The association between socioeconomic-demographic, health behaviors, behavioral and psychological, functional and clinical characteristics and fatigue was examined using generalized estimating equations to account for the longitudinal nature of the data. Results Five-hundred and fifteen patients (~91% female) contributed 2,609 visits to these analyses; there were: 93 (18.1%) Texan Hispanics, 101 (19.6%) Puerto Rican Hispanics, 169 (32.8%) African Americans, and 152 (29.5%) Caucasians; the patients mean (SD) age and follow up time were 37.2 (12.0) and 4.7 (3.2) years, respectively. Variables associated with increased levels of fatigue in the multivariable analyses were Caucasian ethnicity, the presence of constitutional symptoms(fever, weight loss), higher levels of pain, of abnormal illness-related behaviors and of helplessness (p’s between 0.0018 and <0.0001). Conclusions The presence of pain, abnormal illness-related behaviors, helplessness and constitutional manifestations were associated with increased levels of fatigue; however, lupus specific measures, such as disease activity and damage were not. Interventions aimed at decreasing fatigue need to take into account these findings. PMID:19714612

  7. Targeted therapeutics in SLE: emerging strategies to modulate the interferon pathway

    PubMed Central

    Oon, Shereen; Wilson, Nicholas J; Wicks, Ian

    2016-01-01

    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by impaired immune tolerance, resulting in the generation of pathogenic autoantibodies and immune complexes. Although autoreactive B lymphocytes have been the first targets for biologic therapies in SLE, the importance of the innate immune system, and in particular, pathways involved in interferon (IFN) signaling, has emerged. There are now data supporting a central role for a plasmacytoid dendritic cell-derived type I IFN pathway in SLE, with a number of biologic therapeutics and small-molecule inhibitors undergoing clinical trials. Monoclonal antibodies targeting IFN-α have completed phase II clinical trials, and an antibody against the type I IFN receptor is entering a phase III trial. However, other IFNs, such as IFN gamma, and the more recently discovered type III IFNs, are also emerging as targets in SLE; and blockade of upstream components of the IFN signaling pathway may enable inhibition of more than one IFN subtype. In this review, we discuss the current understanding of IFNs in SLE, focusing on emerging therapies. PMID:27350879

  8. Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water

    SciTech Connect

    Kilburn, K.H.; Warshaw, R.H. )

    1992-02-01

    Criteria for the recognition of systemic lupus erythematosus (SLE) were applied to 362 subjects exposed to trichloroethylene, trichloroethane, inorganic chromium, and other chemicals in water obtained from wells in an industrially contaminated aquifer in Tucson, Arizona. Their antinuclear autoantibodies were measured by fluorescence (FANA) in serum. Ten patients with clinical SLE and/or other collagen-vascular diseases were considered separately. Results were compared to an Arizona control group, to published series, and to laboratory controls. Frequencies of each of 10 ARA symptoms were higher in exposed subjects than in any comparison group except those with clinical SLE. The number of subjects with 4 or more symptoms was 2.3 times higher compared to referent women and men. FANA titers > 1:80 was approximately 2.3 times higher in women but equally frequent in men as in laboratory controls. ARA score and FANA rank were correlated with a coefficient (cc) of .1251, r{sup 2} = .0205 in women and this correlation was almost statistically significant in men cc = .1282, r{sup 2} = .0253. In control men and women neither correlation was significant. Long-term low-dose exposure to TCE and other chemicals in contaminated well water significantly increased symptoms of lupus erthematosus as perceived by the ARA score and the increased FANA titers.

  9. [Peculiarities of verbal activity in migraine patients].

    PubMed

    Latysheva, N V; Iakovlev, O N; Filatova, E G

    2003-01-01

    We applied associative verbal experiment to analyze verbal activity of migraineurs. A test group consisted of 49 patients with migraine, a control one--of 20 healthy people. Reliable decrease of free associations number, verbs and plants, semantic index and changes of non-productive association index and coefficient were observed. Average depression level, higher anxiety and negative correlations with indexes calculated were found. Verbal activity of migraineurs, their ability to concentrate and to control adequateness of task fulfillment were decreased. That was caused by pain, depression, anxiety and neurotization. Verbal activity is influenced by individual emotional features (calculated indexes do not correlate with the visual analogue scale). PMID:12938648

  10. Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.

    PubMed Central

    Suzuki, N; Sakane, T; Engleman, E G

    1990-01-01

    Although the presence of anti-DNA antibody is a hallmark of systemic lupus erythematosus (SLE), neither the subsets of B cells that secrete anti-DNA antibody nor the stimuli responsible for the induction of anti-DNA secretion is known. In particular, the role of CD5+ B cells in human SLE, a distinct subpopulation of antibody-secreting cells shown previously to be a source of anti-DNA antibody in murine models of SLE, is unknown. To approach these questions, we developed a sensitive enzyme-linked immunospot (ELIspot) assay to measure spontaneous secretion of antibody to single-stranded (ss) DNA, double-stranded (ds) DNA, tetanus toxoid, and polyclonal immunoglobulin (Ig) by purified CD5+ and CD5- B cells of 15 SLE patients and 15 healthy control subjects. The B cells of only 1 of 15 healthy subjects secreted a significant level of anti-ssDNA antibody, and none secreted anti-dsDNA. By contrast, in the majority of SLE patients both CD5+ and CD5- B cells secreted IgG and/or IgM anti-ssDNA as well as anti-dsDNA antibody. Further analysis of the anti-ssDNA response revealed that the level of IgG and IgM anti-DNA antibody secretion by CD5- B cells correlated closely with the level of polyclonal Ig production by the same subpopulation (r = 0.81 and 0.70, respectively). In contrast, production of anti-DNA by CD5+ B cells occurred independently of polyclonal Ig production by both CD5+ and CD5- B cell subpopulations. These results suggest that in human SLE there exist two anti-DNA antibody-producing B cell subpopulations with distinct induction mechanisms: one (CD5+), which independently secretes anti-DNA, and another (CD5-), which produces anti-DNA as an apparent consequence of polyclonal B cell activation. PMID:1688569

  11. Is lipstick associated with the development of systemic lupus erythematosus (SLE)?

    PubMed

    Wang, Jun; Kay, Ashley B; Fletcher, Jeremiah; Formica, Margaret K; McAlindon, Timothy E

    2008-09-01

    Lipstick use has been hypothesized to be a risk factor of developing systemic lupus erythematosus (SLE). The objective of this study was to investigate the association between lipstick use and risk of SLE. We performed an Internet-based case-control study of SLE with Google users searching on medical key terms as the source population. Cases were diagnosed within 5 years and met > or =4 ACR criteria for SLE by medical record review. Controls were matched to cases on age, gender, race, ethnicity, region of residence, reference year, education, and income using propensity score. Demographic characteristics and lifestyle factors were collected using an online questionnaire. Conditional logistic regression models were used for the analyses with smoking, alcohol consumption, permanent hair dye use, and chemical hair straightener use adjusted. The analysis included 124 cases and 248 matched controls of whom 96% were females and 81% were whites. The median of disease duration was 2 years (range 0-4 years). Using lipstick at least 3 days/week was significantly associated with increased risk of SLE (adjusted OR = 1.71, 95%CI = 1.04-2.82). There was a trend of greater risk with earlier age of initiation of lipstick use (<16 years vs. never use; OR = 1.95, 95%CI = 1.01-3.76, p trend = 0.02) and with increased frequency of use (7 days/week vs. never use; OR = 1.75, 95%CI = 0.89-3.44, p trend = 0.07). Biologic effects of chemicals present in lipsticks absorbed across the buccal mucosa and confounding from unmeasured lifestyle factors could be the explanation of this association. Epidemiologic studies of SLE should include this exposure in exploring its environmental triggers. PMID:18523821

  12. Pregnancy Related Complications in Patients with Systemic Lupus Erythematosus, An Egyptian Experience

    PubMed Central

    Hendawy, S.F.; Abdel-Mohsen, D.; Ebrahim, S.E.; Ewais, H.; Moussa, S.H.; Khattab, D.A.; Mohamed, N.A.; Samaha, H.E.

    2011-01-01

    Background Systemic Lupus Erythematosus (SLE) has a tendency to occur in women in their reproductive years, causing complications during pregnancy and labour. Conversely, pregnancy can cause flares of disease activity, often necessitating immediate intervention. Aim of study to study pregnancy related complications in patients with SLE. Patients and methods The study included 48 SLE pregnant females. 27 patients with 38 pregnancies, their data viewed retrospectively from medical records, and 21 patients with 21 pregnancies followed up prospectively. The laboratory data included ANA, DNA, APL antibodies and anti Ro/SSA. The disease activity was calculated according to the Systemic Lupus Activity Measure. Ultrasound was performed to confirm gestational age and assess for the presence of any congenital fetal malformations, and then repeated monthly to detect any abnormality including intrauterine growth restriction. At 30 weeks gestation and onwards, assessment of fetal wellbeing including daily fetal kick chart and once weekly non stress test was performed. Doppler blood flow velocimetry was done for those with abnormal fetal heart rate pattern. After labour, the neonate was examined for complications including complete heart block and neonatal lupus. Results Anti dsDNA was found in 95% of the patients, anti Ro/SSA in 6% and anti APL in 30%. 57% of the patients followed up prospectively had active disease in the 1st trimester, 24% in the 2nd and 62% in the 3rd trimester. The most common maternal complication was preeclampsia 33%, followed by spontaneous abortion 20%. Prematurity was the most common fetal complication 37%, followed by intrauterine growth restriction 29%. 2 neonates were born with congenital heart block and 1 with neonatal lupus. Conclusion Pregnancy in SLE patients is associated with a higher risk of obstetric complications affecting both the mother and the fetus. Preeclampsia was the most common complication followed by prematurity. Preeclampsia was

  13. Eppur Si Muove: vitamin D is essential in preventing and modulating SLE.

    PubMed

    Azrielant, S; Shoenfeld, Y

    2016-05-01

    Systemic lupus erythematosus (abbreviated SLE or lupus) is a systemic autoimmune disease, with genetic, immunologic, hormonal, and environmental factors.(1)One of the environmental factors that has been studied over the years is vitamin D, which is created in the human body in response to exposure to sunlight and ultraviolet (UV) radiation.This review aims at examining findings from recent years, specifically 2013-2014, regarding the relationship between vitamin D deficiency and SLE flares, severity, and clinical manifestation, as well as to examine the treatment options derived from this relationship. PMID:26811372

  14. A Phase 3, Randomized, Placebo-Controlled Study of Belimumab, a Monoclonal Antibody That Inhibits BLyS, in Patients With Systemic Lupus Erythematosus

    PubMed Central

    Furie, Richard; Petri, Michelle; Zamani, Omid; Cervera, Ricard; Wallace, Daniel J.; Tegzová, Dana; Sanchez-Guerrero, Jorge; Schwarting, Andreas; Merrill, Joan T.; Chatham, W. Winn; Stohl, William; Ginzler, Ellen M.; Hough, Douglas R.; Zhong, Z. John; Freimuth, William; van Vollenhoven, Ronald F.

    2016-01-01

    Objective To assess the efficacy/safety of the B-lymphocyte stimulator inhibitor belimumab/standard-of-care (SOC) versus placebo/SOC in active systemic lupus erythematosus (SLE). Methods In a multicenter, randomized, controlled, phase 3 trial, 819 antinuclear antibody- or anti-dsDNA-positive SLE patients with Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA-SLEDAI) ≥ 6 were randomized (1:1:1 ratio) to receive intravenous belimumab 1 or 10 mg/kg, or placebo on days 0, 14, and 28, and then every 28 days for 72 weeks. Primary efficacy analyses: SLE Responder Index (SRI) at week 52 (≥ 4-point reduction in SELENA-SLEDAI; no new British Isles Lupus Assessment Group A and < 2 new B organ domain scores; no worsening in Physician’s Global Assessment). Results Belimumab 10 mg/kg plus SOC met the primary efficacy endpoint: significantly greater SRI response at week 52 than placebo (43.2% versus 33.5%; P = 0.017); the rate with belimumab 1 mg/kg was 40.6% (P = 0.089). Week-76 response rates: 32.4%, 39.1%, and 38.5% with placebo, and belimumab 1 and 10 mg/kg, respectively. In post-hoc sensitivity analyses evaluating higher SELENA-SLEDAI thresholds, belimumab 10 mg/kg achieved better discrimination at weeks 52/76. Risk of severe SELENA-SLEDAI flares over 76 weeks was reduced with belimumab 1 mg/kg (34%; P = 0.023) and 10 mg/kg (23%; P = 0.13). Serious and severe adverse events including infections, laboratory abnormalities, malignancies, and deaths, were comparable across groups. Conclusion Belimumab plus SOC significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well-tolerated in SLE. PMID:22127708

  15. Hyponatremia in patients with systemic lupus erythematosus

    PubMed Central

    Il Shin, Jae; Park, Se Jin; Suh, Chang-Hee; Lee, Geum Hwa; Hur, Min Woo; Han, Song Yi; Kim, Dong Soo; Kim, Ji Hong

    2016-01-01

    The aim of this study was to determine whether decreased serum sodium concentration could be associated with the disease activity in SLE. We retrospectively analyzed the data of the two independent cohorts of children and adults with SLE in two centers. Hyponatremia was associated with serum chloride (p = 0.004), albumin (p = 0.002) and SLE disease activity index (SLEDAI) (p = 0.026) in children with SLE. Serum sodium levels were correlated negatively with ESR (p =0.001) and positively with serum albumin levels (p < 0.0001) and C3 (p = 0.008) in children with SLE and those levels were correlated negatively with serum interleukin-6 levels (p = 0.003) in adults with SLE. Independent risk factors for the development of hyponatremia were the decreased serum C3 levels (OR 1.069, p = 0.031), the decreased serum chloride levels (OR 2.054, p = 0.006) and increased erythrocyte sedimentation rate (ESR) (OR 1.066, p = 0.03) in children with SLE and increased C-reactive protein (CRP) (OR 1.480, p = 0.023) in combined cohorts with SLE by multiple logistic regression analyses. Our study firstly showed that hyponatremia could reflect a disease activity and severe inflammation of SLE. PMID:27193532

  16. Autoantibodies Affect Brain Density Reduction in Nonneuropsychiatric Systemic Lupus Erythematosus Patients

    PubMed Central

    Xu, Jian; Cheng, Yuqi; Lai, Aiyun; Lv, Zhaoping; Yu, Hongjun; Luo, Chunrong; Shan, Baoci; Xu, Lin; Xu, Xiufeng

    2015-01-01

    This study explores the relationship between autoantibodies and brain density reduction in SLE patients without major neuropsychiatric manifestation (NPSLE). Ninety-five NPSLE patients without obvious cerebral deficits, as determined by conventional MRI, as well as 89 control subjects, underwent high-resolution structural MRI. Whole-brain density of grey matter (GMD) and white matter (WMD) were calculated for each individual, and correlations between the brain density, symptom severity, immunosuppressive agent (ISA), and autoantibody levels were assessed. The GMD and WMD of the SLE group decreased compared to controls. GMD was negatively associated with SLE activity. The WMD of patients who received ISA treatment were higher than that in the patients who did not. The WMD of patients with anticardiolipin (ACL) or anti-SSB/La antibodies was lower than in patients without these antibodies, while the GMD was lower in patients with anti-SM or anti-U1RNP antibodies. Thus, obvious brain atrophy can occur very early even before the development of significant symptoms and specific autoantibodies might contribute to the reduction of GMD or WMD in NPSLE patients. However, ISAs showed protective effects in minimizing GMD and WMD reduction. The presence of these specific autoantibodies might help identify early brain damage in NPSLE patients. PMID:26090505

  17. Autoantibodies Affect Brain Density Reduction in Nonneuropsychiatric Systemic Lupus Erythematosus Patients.

    PubMed

    Xu, Jian; Cheng, Yuqi; Lai, Aiyun; Lv, Zhaoping; Campbell, Robert A A; Yu, Hongjun; Luo, Chunrong; Shan, Baoci; Xu, Lin; Xu, Xiufeng

    2015-01-01

    This study explores the relationship between autoantibodies and brain density reduction in SLE patients without major neuropsychiatric manifestation (NPSLE). Ninety-five NPSLE patients without obvious cerebral deficits, as determined by conventional MRI, as well as 89 control subjects, underwent high-resolution structural MRI. Whole-brain density of grey matter (GMD) and white matter (WMD) were calculated for each individual, and correlations between the brain density, symptom severity, immunosuppressive agent (ISA), and autoantibody levels were assessed. The GMD and WMD of the SLE group decreased compared to controls. GMD was negatively associated with SLE activity. The WMD of patients who received ISA treatment were higher than that in the patients who did not. The WMD of patients with anticardiolipin (ACL) or anti-SSB/La antibodies was lower than in patients without these antibodies, while the GMD was lower in patients with anti-SM or anti-U1RNP antibodies. Thus, obvious brain atrophy can occur very early even before the development of significant symptoms and specific autoantibodies might contribute to the reduction of GMD or WMD in NPSLE patients. However, ISAs showed protective effects in minimizing GMD and WMD reduction. The presence of these specific autoantibodies might help identify early brain damage in NPSLE patients. PMID:26090505

  18. IgG and IgM autoantibody differences in discoid and systemic lupus patients

    PubMed Central

    Chong, Benjamin F.; Tseng, Lin-chiang; Lee, Thomas; Vasquez, Rebecca; Li, Quan Z.; Zhang, Song; Karp, David R.; Olsen, Nancy J.; Mohan, Chandra

    2012-01-01

    Systemic lupus (SLE) patients with discoid lupus (DLE) were reported to have milder disease. To test this observation, we employed sandwich arrays containing 98 autoantigens to compare autoantibody profiles of SLE subjects without DLE (DLE−SLE+) (N=9), SLE subjects with DLE (DLE+SLE+) (N=10), DLE subjects without SLE (DLE+SLE−) (N=11), and healthy controls (N=11). We validated differentially expressed autoantibodies using immunoassays in DLE−SLE+ (N=18), DLE+SLE+ (N=17), DLE+SLE− (N=23), and healthy subjects (N=22). Arrays showed 15 IgG autoantibodies (ten against nuclear antigens) and four IgM autoantibodies that were differentially expressed (q-value<0.05). DLE−SLE+ subjects had higher IgG autoantibodies against dsDNA, ssDNA, dsRNA, histone H2A and H2B, and SS-A (52 kDa) than all other groups including DLE+SLE+ subjects (p<0.05). Immunoassays measuring anti-dsDNA, -ssDNA, and -SS-A (52 kDa) IgG autoantibodies showed similar trends (p<0.05). Healthy and DLE+SLE−subjects expressed higher IgM autoantibodies against alpha beta crystallin, lipopolysaccharide, heat shock cognate 70, and desmoglein-3 than DLE+SLE+ and DLE−SLE+ subjects. IgG:IgM ratios of autoantibodies against nuclear antigens progressively rose from healthy to DLE−SLE+ subjects. In conclusion, lower IgG autoantibodies against nuclear antigens in DLE+SLE+ versus DLE−SLE+ subjects suggest that DLE indicates lower disease severity. Higher IgM autoantibodies against selected antigens in healthy and DLE+SLE−subjects may be non-pathogenic. PMID:22763789

  19. Incidence and Prevalence of Major Central Nervous System Involvement in Systemic Lupus Erythematosus: A 3-Year Prospective Study of 370 Patients

    PubMed Central

    Kampylafka, Eleni I.; Alexopoulos, Haralampos; Kosmidis, Michalis L.; Panagiotakos, Demosthenes B.; Vlachoyiannopoulos, Panayiotis G.; Dalakas, Marinos C.; Moutsopoulos, Haralampos M.; Tzioufas, Athanasios G.

    2013-01-01

    Background The incidence and prevalence of CNS involvement in SLE remains unclear owing to conflicting results in the published studies. The aim of the study was to evaluate the incidence and prevalence of major definite CNS events in SLE patients. Methods 370 SLE patients with no previous history of CNS involvement were prospectively evaluated in a tertiary hospital referral center for 3 years. Major CNS manifestations were codified according to ACR definitions, including chorea, aseptic meningitis, psychosis, seizures, myelopathy, demyelinating syndrome, acute confusional state and strokes. Minor CNS events were excluded. ECLAM and SLEDAI-SELENA Modification scores were used to evaluate disease activity and SLICC/ACR Damage Index was used to assess accumulated damage. Results 16/370 (4.3%) patients presented with a total of 23 major CNS events. These included seizures (35%), strokes (26%), myelopathy (22%), optic neuritis (8.7%), aseptic meningitis (4.3%) and acute psychosis (4.3%). Incidence was 7.8/100 person years. Among hospitalizations for SLE, 13% were due to CNS manifestations. Epileptic seizures were associated with high disease activity, while myelopathy correlated with lower disease activity and NMO-IgG antibodies (P≤0.05). Stroke incidence correlated with APS coexistence (P = 0.06). Overall, CNS involvement correlated with high ECLAM and SLEDAI scores (P<0.001). Conclusions Clinically severe CNS involvement is rare in SLE patients, accounting for 7.8/100 person years. CNS involvement correlates with high disease activity and coexistence of specific features that define the respective CNS syndromes. PMID:23424638

  20. Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

    PubMed Central

    Li, Xiao; Golubovsky, Josh; Hui-Yuen, Joyce; Shah, Ummara; Olech, Ewa; Lomeo, Rosalia; Singh, Vijay; Busch, Howard; Strandberg, Mary Jane; Strandberg, Kayla; Horowitz, Leslie; Askanase, Anca

    2016-01-01

    Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. Results: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 ± 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 ± 5.0 at baseline to 3.5 ± 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. Conclusions: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity. PMID:27158444

  1. Pulmonary embolism in an adolescent girl with negative ACLA systemic lupus erythematosus (SLE): a case report.

    PubMed

    Nabavizadeh, Seyed Hesamedin; Farahbakhsh, Nazanin; Fazel, Ali; Houshmand, Hamidreza; Anushiravani, Amir

    2016-02-01

    Pulmonary involvement is a common manifestation in systemic lupus erythematosus (SLE), whereas pulmonary thromboembolism (PTE) is rarely seen in SLE. PTE related to anti-phospholipid antibody syndrome (APS) is also a rare disease. We have reported a 13-year-old female diagnosed with SLE Two years ago, who is being treated with hydroxychloroquine and prednisolone. She presented with shortness of breath, dry cough, and fever about two weeks prior to admission. She was initially admitted with the diagnosis of pneumonia, but no clinical improvement was seen she was given antibiotics. Hemoptysis was added to her symptoms, so spiral high resolution computed tomography (HRCT) of the lungs was requested, and it indicated patchy consolidations bilaterally. With suspicion of pulmonary thromboembolism (PTE), spiral computed tomography angiography of pulmonary vessels was done, revealing PTE. After initiation of anti-coagulants, her clinical condition and respiratory status improved significantly. We present a rare case of SLE where only lupus anti-coagulant test was abnormal while other tests, such as anti-cardiolipin antibody and anti-phospholipid antibody were normal. Therefore, we can conclude that clinical suspicion had the main role in diagnosis in our case, as it has in medicine. PMID:27053993

  2. ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT, KMC CONTROLS, INC. SLE-1001 SIGHT GLASS MONITOR

    EPA Science Inventory

    The Environmental Technology Verification report discusses the technology and performance of the KMC SLE-1001 Sight Glass Monitor manufactured by KMC Controls, Inc. The sight glass monitor (SGM) fits over the sight glass that may be installed in a refrigeration system for the pur...

  3. Pulmonary embolism in an adolescent girl with negative ACLA systemic lupus erythematosus (SLE): a case report

    PubMed Central

    Nabavizadeh, Seyed Hesamedin; Farahbakhsh, Nazanin; Fazel, Ali; Houshmand, Hamidreza; Anushiravani, Amir

    2016-01-01

    Pulmonary involvement is a common manifestation in systemic lupus erythematosus (SLE), whereas pulmonary thromboembolism (PTE) is rarely seen in SLE. PTE related to anti-phospholipid antibody syndrome (APS) is also a rare disease. We have reported a 13-year-old female diagnosed with SLE Two years ago, who is being treated with hydroxychloroquine and prednisolone. She presented with shortness of breath, dry cough, and fever about two weeks prior to admission. She was initially admitted with the diagnosis of pneumonia, but no clinical improvement was seen she was given antibiotics. Hemoptysis was added to her symptoms, so spiral high resolution computed tomography (HRCT) of the lungs was requested, and it indicated patchy consolidations bilaterally. With suspicion of pulmonary thromboembolism (PTE), spiral computed tomography angiography of pulmonary vessels was done, revealing PTE. After initiation of anti-coagulants, her clinical condition and respiratory status improved significantly. We present a rare case of SLE where only lupus anti-coagulant test was abnormal while other tests, such as anti-cardiolipin antibody and anti-phospholipid antibody were normal. Therefore, we can conclude that clinical suspicion had the main role in diagnosis in our case, as it has in medicine. PMID:27053993

  4. IL-2 enhancing factor(s) in B cell supernatants from patients with rheumatoid arthritis or systemic lupus erythematosus.

    PubMed

    Tomura, K; Kang, H; Mitamura, K; Takei, M; Karasaki, M; Koyasu, S; Sawada, S

    1989-11-01

    Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15,000 and 20,000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy volunteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE. PMID:2623661

  5. Belimumab for the treatment of corticosteroid-dependent systemic lupus erythematosus: from clinical trials to real-life experience after 1 year of use in 48 Brazilian patients.

    PubMed

    Scheinberg, Morton; de Melo, Flavio Fernando Nogueira; Bueno, Adrian Nogueira; Costa, Carolyne Mendes; de Azevedo Bahr, Maria Lucia Alvares; Reis, Enio Ribeiro

    2016-07-01

    The objective of the study was to evaluate prospectively real-life experience on the effect of belimumab on patients with active systemic lupus erythematosus (SLE). Forty-eight patients with active SLE were evaluated after 1 year of continuous treatment. Thirty-eight patients were still on treatment at the end of 1 year, and it was possible to observe significant clinical improvement in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score with a decrease from 12 ± 3.0 to 2.5 ± 2.5, also a decrease on the daily steroid dose from 30 ± 12.5 to 7.5 ± 5.0 mg and partial improvement on serology. Belimumab treatment is associated with real benefit in the majority of patients that maintain active disease in spite of continuing on standard of care. PMID:27106543

  6. Identification of MAMDC1 as a Candidate Susceptibility Gene for Systemic Lupus Erythematosus (SLE)

    PubMed Central

    Hellquist, Anna; Zucchelli, Marco; Lindgren, Cecilia M.; Saarialho-Kere, Ulpu; Järvinen, Tiina M.; Koskenmies, Sari; Julkunen, Heikki; Onkamo, Päivi; Skoog, Tiina; Panelius, Jaana; Räisänen-Sokolowski, Anne; Hasan, Taina; Widen, Elisabeth; Gunnarson, Iva; Svenungsson, Elisabet; Padyukov, Leonid; Assadi, Ghazaleh; Berglind, Linda; Mäkelä, Ville-Veikko; Kivinen, Katja; Wong, Andrew; Cunningham Graham, Deborah S.; Vyse, Timothy J.; D'Amato, Mauro; Kere, Juha

    2009-01-01

    Background Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with multiple susceptibility genes. We have previously reported suggestive linkage to the chromosomal region 14q21-q23 in Finnish SLE families. Principal Findings Genetic fine mapping of this region in the same family material, together with a large collection of parent affected trios from UK and two independent case-control cohorts from Finland and Sweden, indicated that a novel uncharacterized gene, MAMDC1 (MAM domain containing glycosylphosphatidylinositol anchor 2, also known as MDGA2, MIM 611128), represents a putative susceptibility gene for SLE. In a combined analysis of the whole dataset, significant evidence of association was detected for the MAMDC1 intronic single nucleotide polymorphisms (SNP) rs961616 (P –value = 0.001, Odds Ratio (OR) = 1.292, 95% CI 1.103–1.513) and rs2297926 (P –value = 0.003, OR = 1.349, 95% CI 1.109–1.640). By Northern blot, real-time PCR (qRT-PCR) and immunohistochemical (IHC) analyses, we show that MAMDC1 is expressed in several tissues and cell types, and that the corresponding mRNA is up-regulated by the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in THP-1 monocytes. Based on its homology to known proteins with similar structure, MAMDC1 appears to be a novel member of the adhesion molecules of the immunoglobulin superfamily (IgCAM), which is involved in cell adhesion, migration, and recruitment to inflammatory sites. Remarkably, some IgCAMs have been shown to interact with ITGAM, the product of another SLE susceptibility gene recently discovered in two independent genome wide association (GWA) scans. Significance Further studies focused on MAMDC1 and other molecules involved in these pathways might thus provide new insight into the pathogenesis of SLE. PMID:19997561

  7. Systemic lupus erythematosus activity. An operational definition.

    PubMed

    Liang, M H; Stern, S; Esdaile, J M

    1988-04-01

    Improved diagnosis and treatment have reduced mortality from SLE and present us with an opportunity to consider SLE in finer distinctions than alive or dead. Although much has been learned about SLE without a gold standard of disease activity or a universally agreed-upon definition of SLE activity, standardization of one or more measures would greatly enhance our ability to compare results from different centers and to communicate more precisely. It is unlikely that any of the existing measures or any ones to be developed will completely satisfy everyone's needs but it is pointless to proliferate new ones without testing their metric properties. Some differences in concept are desirable, particularly for investigators who have specialized interests or insights, but each should meet criteria of reliability and validity and have explicit definitions of terms, rules for their ascertainment, and the time period covered. Moreover, agreement on minimum essential elements of any SLE activity measure and their operational definitions would be a boon. SLE activity is one dimension in the disease pathway of lupus and implies a continuous phenomena that is potentially reversible. Organ damage, another point in the path of causation, connotes irreversible disease. We recommend that minimum essential elements be based on their frequency of occurrence, biological sensibleness, and the likelihood that degrees of activity can be rated reliably to show a change in a clinical state. The rating should be independent of whether a therapy is employed. Since activity is always considered with severity, the two dimensions could be recognized in the scale. Severity can be used to expand a scale's gradations if a symptom or sign is present. Severity could be rated by the need to treat with immunosuppressive agents, the need to follow the patient more closely, or the functional or prognostic consequences of the manifestation. For every organ system clinical judgment should be used to decide

  8. Inflammatory cytokine kinetics to single bouts of acute moderate and intense aerobic exercise in women with active and inactive systemic lupus erythematosus.

    PubMed

    Perandini, L A; Sales-de-Oliveira, D; Mello, Sbv; Camara, N O; Benatti, F B; Lima, F R; Borba, E; Bonfa, E; Roschel, H; Sá-Pinto, A L; Gualano, B

    2015-01-01

    the end of exercise and at the 30th minute of recovery (P<0.05). The SLE(ACTIVE) group also showed higher levels of TNF-α at all time points when compared with the HC group (P<0.05), (except after 90 min, 120 min and 24 hours of recovery) (P>0.05). Importantly, the levels of all cytokine and soluble TNF receptors returned to baseline 24 hours after the end of acute exercise, irrespective of its intensity, in all three groups (P>0.05). This study demonstrated that both the single bouts of acute moderate and intense exercise induced mild and transient changes in cytokine levels in both SLE(INACTIVE) and SLE(ACTIVE) women, providing novel evidence that acute aerobic exercise does not trigger inflammation in patients with this disease. PMID:25825870

  9. Association of age with health-related quality of life in a cohort of patients with systemic lupus erythematosus: the Georgians Organized Against Lupus study

    PubMed Central

    Plantinga, Laura; Lim, S Sam; Bowling, C Barrett; Drenkard, Cristina

    2016-01-01

    Objective To examine whether older age was associated with lower health-related quality of life (HRQOL) among patients with systemic lupus erythematosus (SLE) and whether differential disease-related damage and activity explained these associations. Methods We used cross-sectional data on 684 patients with SLE aged ≥20 years from the Georgians Organized Against Lupus cohort to estimate the associations between age (categorised as 20–39, 40–59 and ≥60 years) and HRQOL (Short Form-12 norm-based domain and physical component summary (PCS) and mental component summary (MCS) scores), using multivariable linear regression. We then examined the effect of disease-related damage and activity on these associations. Results The mean age of the cohort was 48.2±13.1 years (range, 20–88 years), with 28.0%, 52.9% and 19.1% of participants being aged 20–39, 40–59 and ≥60 years, respectively; 79.0% were African-American and 93.7% were female. The mean PCS score was 39.3 (41.8, 38.7 and 37.4 among those aged 20–39, 40–59 and ≥60 years, respectively), while the mean MCS score was 44.3 (44.2, 43.8 and 46.1, respectively). In general, lower physical but not mental HRQOL scores were associated with older age. With adjustment, older ages (40–59 and ≥60, respectively, vs 20–39) remained associated (β (95% CI)) with lower PCS (−2.53 (−4.58 to −0.67) and −3.57 (−6.19 to −0.96)) but not MCS (0.47 (−1.46 to 2.41) and 1.20 (−1.52 to 3.92)) scores. Associations of age with HRQOL domain and summary scores were not substantially changed by further adjustment for disease-related damage and/or activity. Conclusions Nearly one in five participants in this large, predominantly African-American cohort of patients with SLE was at least 60 years old. The associations of older age with lower physical, but not mental, HRQOL were independent of accumulated SLE damage and current SLE activity. The results suggest that studies of important geriatric

  10. Characterization of DNA in polyethylene glycol precipitated immune complexes from sera of patients with systemic lupus erythematosus.

    PubMed Central

    Ikebe, K; Gupta, R C; Tan, E M

    1983-01-01

    The nature and the quantity of DNA present in the circulating immune complexes (ICs) from 30 patients with systemic lupus erythematosus (SLE) was characterized. DNA was extracted from IC enriched material prepared by polyethylene glycol precipitation of serum and the extracted DNA was labelled with 32P-phosphate. The size and the nature of DNA was determined by polyacrylamide gel electrophoresis and autoradiography. The quantity of DNA in the PEG precipitates from sera of 10 clinically active SLE was found to be significantly higher (mean 159 X 10(4) ct/min, range 49.9-807 X 10(4) ct/min) than 10 normal controls (mean 24.7 X 10(4) ct/min, range 8.7-47.8 X 10(4) ct/min). Four different sizes of DNA fragments were detected: 370-470, 150-240, 30-40 and 20 base pairs (bp). DNA of 30-40 bp and 20 bp were frequently present in both SLE and normals, but the other two large sized DNA fragments were particularly prominent in SLE patients. In the majority of samples, DNA fragments appeared double stranded. Images Fig. 3 Fig. 4 Fig. 5 PMID:6616966

  11. Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study

    PubMed Central

    Wallace, Daniel J; Kalunian, Kenneth; Petri, Michelle A; Strand, Vibeke; Houssiau, Frederic A; Pike, Marilyn; Kilgallen, Brian; Bongardt, Sabine; Barry, Anna; Kelley, Lexy; Gordon, Caroline

    2014-01-01

    Objective To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). Methods A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37–39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Results Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Conclusions Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing. PMID:23313811

  12. Risk of Peripheral Arterial Occlusive Disease in Patients With Systemic Lupus Erythematosus

    PubMed Central

    Chuang, Ya-Wen; Yu, Mei-Ching; Lin, Cheng-Li; Yu, Tung-Min; Shu, Kuo-Hsiung; Kao, Chia-Hung

    2015-01-01

    Abstract Systemic lupus erythematosus (SLE) is associated with atherosclerosis, but the relationship between SLE and peripheral arterial occlusive disease (PAOD) remains unclear. We sought to investigate this relationship by comparing cardiovascular complications in patients with and without SLE. Data on patients from 2000 to 2011 were collected from the National Health Insurance Research Database of Taiwan. The SLE cohort was frequency-matched according to age, sex, and history of diabetes mellitus (DM) with patients without SLE (control cohort). We evaluated the risk of cardiovascular complications, including hypertension, DM, stroke, chronic obstructive pulmonary disease, heart failure, coronary artery disease, and hyperlipidemia. The study included 10,144 patients with SLE and 10,144 control patients. The incidence of PAOD was 9.39-fold higher (95% confidence interval [CI] = 7.70–11.15) in the SLE cohort than in the non-SLE cohort. Moreover, SLE was an independent risk factor for PAOD. The adjusted risk of PAOD was highest in patients with SLE who were aged ≤34 years (hazard ratio = 47.6, 95% CI = 26.8–84.4). The risk of PAOD was highest during the first year of follow-up and decreased over time. Patients with SLE exhibit a higher incidence and an independently higher risk of PAOD compared with the general population. The PAOD risk is markedly elevated in patients with SLE who are young and in whom the disease is at an early stage. PMID:26579830

  13. Adalimumab in Patients with Active Noninfectious Uveitis.

    PubMed

    Jaffe, Glenn J; Dick, Andrew D; Brézin, Antoine P; Nguyen, Quan Dong; Thorne, Jennifer E; Kestelyn, Philippe; Barisani-Asenbauer, Talin; Franco, Pablo; Heiligenhaus, Arnd; Scales, David; Chu, David S; Camez, Anne; Kwatra, Nisha V; Song, Alexandra P; Kron, Martina; Tari, Samir; Suhler, Eric B

    2016-09-01

    Background Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. Methods This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. Results The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events

  14. CD3+CD8+CD28− T Lymphocytes in Patients with Lupus Nephritis

    PubMed Central

    Krajewska, Magdalena

    2016-01-01

    The results of studies on the CD3+CD8+CD28− cells in SLE are inconsistent since several analyses describe CD3+CD8+CD28− as either immunosuppressive or cytotoxic. The aim of this study is to inquire whether the quantitative changes of CD3+CD8+CD28− T lymphocytes subpopulation are related to the clinical status of patients with lupus nephritis. Evaluation of Foxp3 expression on CD3+CD8+CD28− cells may shed some light on functional properties of these cells. 54 adult SLE patients and 19 sex and age matched healthy volunteers were enrolled in the study. There were 15 patients in inactive (SLEDAI ≤ 5) and 39 in active (SLEDAI > 5) phase of disease. We determined absolute count of CD3+CD8+CD28− and CD3+CD8+CD28−Foxp3+ subpopulations by flow cytometry. We observed a statistically significant increase in absolute count and percentage of CD3+CD8+CD28− in SLE patients compared to HC (p < 0.001). Moreover there was significant positive correlation between increasing absolute count of CD3+CD8+CD28− cells and disease activity measured by SLEDAI (rs = 0.281, p = 0.038). Active LN patients had increased absolute count of CD3+CD8+CD28− cells compared to HC. Positive correlation of CD3+CD8+CD28− number with disease activity, and lack of Foxp3 expression on these cells, suggests that CD3+CD8+CD28− lymphocytes might be responsible for an increased proinflammatory response in the exacerbation of SLE. PMID:27446964

  15. CD3(+)CD8(+)CD28(-) T Lymphocytes in Patients with Lupus Nephritis.

    PubMed

    Żabińska, Marcelina; Krajewska, Magdalena; Kościelska-Kasprzak, Katarzyna; Klinger, Marian

    2016-01-01

    The results of studies on the CD3(+)CD8(+)CD28(-) cells in SLE are inconsistent since several analyses describe CD3(+)CD8(+)CD28(-) as either immunosuppressive or cytotoxic. The aim of this study is to inquire whether the quantitative changes of CD3(+)CD8(+)CD28(-) T lymphocytes subpopulation are related to the clinical status of patients with lupus nephritis. Evaluation of Foxp3 expression on CD3(+)CD8(+)CD28(-) cells may shed some light on functional properties of these cells. 54 adult SLE patients and 19 sex and age matched healthy volunteers were enrolled in the study. There were 15 patients in inactive (SLEDAI ≤ 5) and 39 in active (SLEDAI > 5) phase of disease. We determined absolute count of CD3(+)CD8(+)CD28(-) and CD3(+)CD8(+)CD28(-)Foxp3(+) subpopulations by flow cytometry. We observed a statistically significant increase in absolute count and percentage of CD3(+)CD8(+)CD28(-) in SLE patients compared to HC (p < 0.001). Moreover there was significant positive correlation between increasing absolute count of CD3(+)CD8(+)CD28(-) cells and disease activity measured by SLEDAI (rs = 0.281, p = 0.038). Active LN patients had increased absolute count of CD3(+)CD8(+)CD28(-) cells compared to HC. Positive correlation of CD3(+)CD8(+)CD28(-) number with disease activity, and lack of Foxp3 expression on these cells, suggests that CD3(+)CD8(+)CD28(-) lymphocytes might be responsible for an increased proinflammatory response in the exacerbation of SLE. PMID:27446964

  16. [Tissue grafts: an activity concerning many patients].

    PubMed

    Loty, B

    1997-11-15

    Tissue allografts mainly include corneas, bone (and cartilage, tendon, ligament, aponevrosis), skin, vessels and cardiac valves. All these grafts have been widely used for many years and were the subject of a large number of experimental and clinical studies. The different steps allowing the obtention of different tissue allografts have in fact a common organization through tissue procurement and banking activities. Tissue banks have a central situation ensuring security, safety, traceability and distribution of tissues. Appropriate organization of the banks, and respect of high level standards are thus mandatory. Tissue transplantation activity in France has been studied through national surveys: they concern more than 600 hospitals and clinics, and grafts procured in France (excluding imported allografts) are around 15,000 a year. Precise regulation implied by the bioethical law published in 1994 and homogeneous organization of the activity allow the use of stringent and regularly updated standards, allowing the distribution to the patients of safe grafts procured in ethical conditions. The actual shortage of tissue allografts in France implies increasing procurement through a better organization of retrieval in hospitals and clinics and donation promotion. PMID:9501596

  17. Effect of acute cytomegalovirus infection on drug-induced SLE.

    PubMed Central

    Schattner, A.; Sthoeger, Z.; Geltner, D.

    1994-01-01

    A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity. PMID:7831173

  18. Association of the polymorphisms of TRAF1 (rs10818488) and TNFAIP3 (rs2230926) with rheumatoid arthritis and systemic lupus erythematosus and their relationship to disease activity among Egyptian patients

    PubMed Central

    Mohannad, Nevine

    2016-01-01

    Aim of the study Recent studies demonstrated the association of tumor necrosis factor α-induced protein 3 (TNFAIP3) (rs2230926) and tumor necrosis factor receptor associated factor 1 (TRAF1) (rs10818488) with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in different populations. We aimed at determining whether they confer susceptibility to SLE and RA in Egyptian population and if there is any relation to disease activity and auto-antibodies profile. Material and methods A case-control study involving 105 individuals with RA, 90 with SLE and 75 healthy controls was performed using TaqMan genotyping assay for two SNPs that showed the best evidence of association in the previous Caucasian studies. Results We detected significant differences in G allele frequency of TNFAIP3 (rs2230926) with SLE (p = 0.017*) and RA (OR = 2.333; 95% CI: 1.103-4.935, p = 0.023*) and association with RA disease activity (< 0.001). The A allele of TRAF1 was significantly increased in RA compared to controls(p = 0.049) and with RA activity (p = 0.001), while TRAF1 polymorphism did not exhibit any significant difference in the frequencies of genotypes or alleles in SLE and control (p = 0.280). Conclusions TNFAIP3 is a susceptibility gene to SLE and RA in the Egyptian population and is correlated to disease activity and the presence of autoantibodies while TRAF1 polymorphisms increase the risk of RA but not to SLE in Egyptian populations. PMID:27536202

  19. Analysis of T cells bearing different isotypic forms of the gamma/delta T cell receptor in patients with systemic autoimmune diseases.

    PubMed

    Gerli, R; Agea, E; Bertotto, A; Tognellini, R; Flenghi, L; Spinozzi, F; Velardi, A; Grignani, F

    1991-10-01

    The expression of gamma/delta T cell receptor (TCR) on peripheral blood CD3+ cells circulating in 74 patients with different systemic autoimmune diseases was evaluated. There was a significant increase in the gamma/delta T cell number only in patients with primary Sjögren's syndrome (SS) and in untreated patients with systemic lupus erythematosus (SLE). Unlike healthy subjects, a subgroup of patients with SLE and SS displayed a marked increase in gamma/delta T cells. Immunosuppressive treatment of patients with active SLE led to a normalization of the gamma/delta T cell number. Analysis of surface phenotype showed that when patient gamma/delta T cells were expanded in the peripheral blood, they were not activated but bore "memory" markers. In addition, they preferentially expressed the disulfide linked form of the TCR, except in progressive systemic sclerosis where the nondisulfide form was displayed. Serial determinations in single patients demonstrated that the gamma/delta T cell increase is a persistent immunological feature in these patient subgroups. PMID:1837314

  20. Belimumab Reduces Autoantibodies, Normalizes Low Complement, and Reduces Select B-Cell Populations in Patients With Systemic Lupus Erythematosus

    PubMed Central

    STOHL, WILLIAM; HIEPE, FALK; LATINIS, KEVIN M.; THOMAS, MATHEW; SCHEINBERG, MORTON A.; CLARKE, ANN; ARANOW, CYNTHIA; WELLBORNE, FRANK R.; ABUD-MENDOZA, CARLOS; HOUGH, DOUGLAS R.; PINEDA, LILIA; MIGONE, THI-SAU; ZHONG, Z. JOHN; FREIMUTH, WILLIAM W.; CHATHAM, W. WINN

    2012-01-01

    Objective To assess the effects of the B-lymphocyte stimulator (BLyS)-specific inhibitor belimumab on immunologic biomarkers, including B- and T-cell populations, and maintenance of antibody titers to prior vaccines in autoantibody-positive systemic lupus erythematosus (SLE) patients. Methods Pooled data from two phase 3 trials—BLISS-52 and -76—comparing belimumab 1 or 10 mg/kg vs placebo (each plus standard SLE therapy) were analyzed for changes in autoantibodies, immunoglobulin (Ig), and complement (C); BLISS-76 patients were analyzed for changes in B- and T-cell populations, and effects on prior vaccine-induced antibody levels. Results Belimumab-treated patients experienced significant sustained reductions in IgG and autoantibodies, and improvement in C3/C4, resulting in greater positive-to-negative conversion rates for IgG anti–double-stranded DNA (anti-dsDNA), anti-Smith, anticardiolipin, and antiribosomal P autoantibodies, and normalization of hypergammaglobulinemia and low C3/C4. Belimumab-treated patients experienced significant decreases in naïve and activated B cells, as well as plasma cells, whereas memory B cells and T-cell populations did not decrease. Belimumab did not substantially affect pre-existing antipneumococcal or antitetanus antibody levels. Post-hoc analysis showed greater reductions in SLE disease activity and the risk of severe flares in patients treated with belimumab 10 mg/kg (P ≤ 0.01) who were anti-dsDNA positive with low C3/C4 at baseline. Normalization of C3 or anti-dsDNA by 8 weeks, irrespective of therapy, was predictive of a reduced risk of severe flare over 52 weeks. Conclusion Belimumab appears to promote normalization of serologic activity and reduce BLyS-dependent B-cell subsets in serologically and clinically active SLE. Greater serologic activity may predict a better treatment response to belimumab. PMID:22275291

  1. Schramm-Loewner (SLE) analysis of quasi two-dimensional turbulent flows

    NASA Astrophysics Data System (ADS)

    Thalabard, Simon

    2012-02-01

    Quasi two-dimensional turbulence can be observed in several cases: for example, in the laboratory using liquid soap films, or as the result of a strong imposed rotation as obtained in three-dimensional large direct numerical simulations. We study and contrast SLE properties of such flows, in the former case in the inverse cascade of energy to large scale, and in the latter in the direct cascade of energy to small scales in the presence of a fully-helical forcing. We thus examine the geometric properties of these quasi 2D regimes in the context of stochastic geometry, as was done for the 2D inverse cascade by Bernard et al. (2006). We show that in both cases the data is compatible with self-similarity and with SLE behaviors, whose different diffusivities can be heuristically determined.

  2. Presence of antibodies against cyclic citrullinated peptides in patients with 'rhupus': a cross-sectional study

    PubMed Central

    Amezcua-Guerra, Luis M; Springall, Rashidi; Marquez-Velasco, Ricardo; Gómez-García, Lorena; Vargas, Angélica; Bojalil, Rafael

    2006-01-01

    'Rhupus' is a rare condition sharing features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). If rhupus is a distinctive entity, an overlap between RA and SLE or a subset of SLE is currently debated. This study was performed to explore the prevalence of antibodies against cyclic citrullinated peptides (anti-CCP antibodies) in rhupus. Patients meeting American College of Rheumatology criteria for RA, SLE, or both were included. Clinical and radiographic features were recorded and sera were searched for anti-CCP antibodies, rheumatoid factor, antinuclear antibodies, anti-extractable nuclear antigens, and antibodies against double-stranded DNA (anti-dsDNA antibodies). Seven patients for each group were included. Clinical and serological features for RA or SLE were similar between rhupus and RA patients, and between rhupus and SLE patients, respectively. Values for anti-CCP antibodies obtained were significantly (p < 0.05) higher in RA (6/7) and rhupus (4/7) than in SLE patients (0/7) and healthy subjects (0/7). Our data support the possibility that rhupus is an overlap between RA and SLE, because highly specific autoantibodies for RA (anti-CCP) and for SLE (anti-dsDNA and anti-Sm) are detected in coexistence. PMID:16934155

  3. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1

    PubMed Central

    Bonsignori, Mattia; Wiehe, Kevin; Grimm, Sebastian K.; Lynch, Rebecca; Yang, Guang; Kozink, Daniel M.; Perrin, Florence; Cooper, Abby J.; Hwang, Kwan-Ki; Chen, Xi; Liu, Mengfei; McKee, Krisha; Parks, Robert J.; Eudailey, Joshua; Wang, Minyue; Clowse, Megan; Criscione-Schreiber, Lisa G.; Moody, M. Anthony; Ackerman, Margaret E.; Boyd, Scott D.; Gao, Feng; Kelsoe, Garnett; Verkoczy, Laurent; Tomaras, Georgia D.; Liao, Hua-Xin; Kepler, Thomas B.; Montefiori, David C.; Mascola, John R.; Haynes, Barton F.

    2014-01-01

    Broadly HIV-1–neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1–infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1–infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient’s plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells. PMID:24614107

  4. Joint Polar Satellite System (JPSS) Common Ground System (CGS) Use of Space Link Extension (SLE) Protocol

    NASA Astrophysics Data System (ADS)

    Jamilkowski, M. L.; Cordier, G. R.; Johnson, L. M.; Tillery, C. J.

    2014-12-01

    NOAA & NASA are acquiring the next-generation civilian operational weather satellite -- Joint Polar Satellite System (JPSS). Contributing the afternoon orbit & ground system (GS) to replace current NOAA POES Satellites, its sensors will collect meteorological, oceanographic, climatological & solar-geophysical data. The JPSS Common Ground System (CGS), consisting of Command, Control & Communications (C3) and Interface Data Processing (IDP) segments, is developed by Raytheon. CGS now flies the Suomi National Polar-orbiting Partnership (S-NPP) satellite, transferring data between ground facilities, processing them into Environmental Data Records for NOAA & DoD weather centers, and expanding to support JPSS-1 in 2017. CGS Block 2.0 (B2.0) is the recent CDR-approved design to support both the current S-NPP and upcoming JPSS-1 missions. In B2.0, many important improvements were made to evolve CGS C3. One of those improvements is the addition of SLE services. The CCSDS SLE Protocol standard facilitates and significantly improves GS-to-Data Center communications. The CGS SLE architecture provides data reliability and resource scheduling and is scalable to support added missions. The JPSS CGS is a mature, tested solution for supporting operational weather forecasting for civil, military, and international partners as well as climate research. It features a flexible design that handles order-of-magnitude increases in data over legacy satellite ground systems and meets demanding science accuracy needs. The JPSS CGS is expandable to support additional ground station service providers with or without the deployment of additional JPSS ground hardware by using standard SLE Transfer Service protocol and offers opportunities to reduce costs and improve information Integration across missions. The Raytheon-built JPSS CGS provides the full common ground capability, from design and development through operations & sustainment. These features lay the foundation for the CGS future

  5. Encore: Genetic Association Interaction Network Centrality Pipeline and Application to SLE Exome Data

    PubMed Central

    Davis, Nicholas A.; Lareau, Caleb A.; White, Bill C.; Pandey, Ahwan; Wiley, Graham; Montgomery, Courtney G.; Gaffney, Patrick M.; McKinney, B.A.

    2014-01-01

    Open source tools are needed to facilitate the construction, analysis, and visualization of gene-gene interaction networks for sequencing data. To address this need, we present Encore, an open source network analysis pipeline for GWAS and rare variant data. Encore constructs Genetic Association Interaction Networks or Epistasis Networks using two optional approaches: our previous information-theory method or a generalized linear model approach. Additionally, Encore includes multiple data filtering options, including Random Forest/Random Jungle for main effect enrichment and Evaporative Cooling and Relief-F filters for enrichment of interaction effects. Encore implements SNPrank network centrality for identifying susceptibility hubs (nodes containing a large amount of disease susceptibility information through the combination of multivariate main effects and multiple gene-gene interactions in the network), and it provides appropriate files for interactive visualization of a network using tools from our online Galaxy instance. We implemented these algorithms in C++ using OpenMP for shared-memory parallel analysis on a server or desktop. To demonstrate Encore’s utility in analysis of genetic sequencing data, we present an analysis of exome resequencing data from healthy individuals and those with Systemic Lupus Erythematous (SLE). Our results verify the importance of the previously associated SLE genes HLA-DRB and NCF2, and these two genes had the highest gene-gene interaction degrees among the susceptibility hubs. An additional 14 genes previously associated with SLE emerged in our epistasis network model of the exome data, and three novel candidate genes, ST8SIA4, CMTM4, and C2CD4B, were implicated in the model. In summary, we present a comprehensive tool for epistasis network analysis and the first such analysis of exome data from a genetic study of SLE. Software Availability: http://insilico.utulsa.edu/encore.php. PMID:23740754

  6. Gastric mucosal injury in systemic lupus erythematosus patients receiving pulse methylprednisolone therapy

    PubMed Central

    Luo, Jiing-Chyuan; Chang, Full-Young; Chen, Tseng-Shing; Ng, Yee-Yung; Lin, Han-Chieh; Lu, Ching-Liang; Chen, Chih-Yen; Lin, Hsiao-Yi; Lee, Shou-Dong

    2009-01-01

    AIMS Whether glucocorticoids induce gastric mucosal injury remains uncertain. We investigated whether very high-dose steroids caused gastric mucosal injury in systemic lupus erythematous (SLE) patients and evaluated the possible risk factors for mucosal injury. METHODS In this prospective paired study, 67 SLE patients who had received pulse methylprednisolone therapy were enrolled. Each patient underwent endoscopic examination and tissue and blood sampling before and after pulse steroid therapy. Mucosal injury was diagnosed if the follow-up injury scale was higher than the initial scale. Examined parameters included Helicobacter pylori infection, cyclooxygenase (COX)-1 and COX-2 activity, and current nonsteroidal anti-inflammatory drug (NSAID) usage including aspirin. RESULTS Eleven (16.4%) of 67 cases who developed gastric mucosal injury after pulse therapy had significantly higher rates of peptic ulcer history, NSAID/aspirin use, lower gastric thromboxane B2 and prostaglandin E2 levels when compared with cases without gastric mucosal injury (P < 0.05). Infection by H. pylori was not a risk factor for gastric mucosal injury. Multivariate logistic regression analysis showed that NSAID/aspirin use was the only risk factor for gastric mucosal injury in these patients (odds ratio 26.99, 95% confidence interval 4.91, 148.57, P < 0.0001). Pulse steroid therapy alone did not induce gastric mucosal injury in fifty SLE patients without taking any NSAID/aspirin. CONCLUSIONS Use of NSAIDs/aspirin, but not H. pylori infection, increases gastric mucosal injury in SLE patients receiving pulse methylprednisolone therapy. Very high-dose steroids de novo seem not to induce gastric mucosal injury in these patients. A larger case-controlled study enrolling a heterogeneous population is needed to clarify the role of glucocorticoids in gastric mucosal injury. PMID:19694746

  7. GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.

    PubMed

    Armstrong, D L; Zidovetzki, R; Alarcón-Riquelme, M E; Tsao, B P; Criswell, L A; Kimberly, R P; Harley, J B; Sivils, K L; Vyse, T J; Gaffney, P M; Langefeld, C D; Jacob, C O

    2014-09-01

    In a genome-wide association study (GWAS) of individuals of European ancestry afflicted with systemic lupus erythematosus (SLE) the extensive utilization of imputation, step-wise multiple regression, lasso regularization and increasing study power by utilizing false discovery rate instead of a Bonferroni multiple test correction enabled us to identify 13 novel non-human leukocyte antigen (HLA) genes and confirmed the association of four genes previously reported to be associated. Novel genes associated with SLE susceptibility included two transcription factors (EHF and MED1), two components of the NF-κB pathway (RASSF2 and RNF114), one gene involved in adhesion and endothelial migration (CNTN6) and two genes involved in antigen presentation (BIN1 and SEC61G). In addition, the strongly significant association of multiple single-nucleotide polymorphisms (SNPs) in the HLA region was assigned to HLA alleles and serotypes and deconvoluted into four primary signals. The novel SLE-associated genes point to new directions for both the diagnosis and treatment of this debilitating autoimmune disease. PMID:24871463

  8. Comparing demographics, clinical presentation, treatments and outcome between systemic lupus erythematosus patients treated in a public and private health system in Santa Fe, Argentina.

    PubMed

    Schmid, María Marcela; Roverano, Susana Graciela; Paira, Sergio Oscar

    2014-01-01

    The study includes 159 SLE patients seen between 1987 and 2011, of whom 116 were treated in the public health system and 43 in private practice. In the comparison between both groups, it was shown that patients in the public health system were younger at first consultation and at the onset of SLE, and that the mean duration of their disease prior to nephropathy was statistically significantly shorter. They also presented with more SLE activity (measured by Systemic Lupus Erythematosus Activity Index) such as fever, lower levels of C4, and elevated erythrocyte sedimentation rate. Although cyclophosphamide was administered more frequently to patients in the public health system group, there were no statistically significant differences in renal histological findings. A second renal biopsy was performed on 20 patients due to the presence of persistent proteinuria, peripheral edema, urinary casts, or because of previous defective renal specimens. The overall 10-year survival of the patients in the public health system was 78% compared to a survival rate of 91% for the patients in private practices. When survival was evaluated at 15 years, however, no differences were found (log rank test: 0.65). Patients from both public and private groups attended medical specialist practices and received early diagnoses and close follow-ups. PMID:24984924

  9. Exploring Contextual Factors and Patient Activation: Evidence from a Nationally Representative Sample of Patients with Depression

    ERIC Educational Resources Information Center

    Chen, Jie; Mortensen, Karoline; Bloodworth, Robin

    2014-01-01

    Patient activation has been considered as a "blockbuster drug of the century." Patients with mental disorders are less activated compared to patients with other chronic diseases. Low activation due to mental disorders can affect the efficiency of treatment of other comorbidities. Contextual factors are significantly associated with…

  10. Factors influencing the health related quality of life in patients with systemic lupus erythematosus: long-term results (2001--2005) of patients in the German Lupus Erythematosus Self-Help Organization (LULA Study).

    PubMed

    Tamayo, T; Fischer-Betz, R; Beer, S; Winkler-Rohlfing, B; Schneider, M

    2010-12-01

    The aim of this longitudinal study was to determine disease-specific and individual factors associated with health-related quality of life (HRQOL) in a cohort of patients with systemic lupus erythematosus (SLE) organized in the German Lupus Erythematosus Self-Help Organization. Three hundred and seventeen patients aged between 11 and 77 years participated annually in five surveys carried out between 2001 and 2005. Regression analyses were carried out for physical and mental HRQOL as dependent variables. Factors influencing HRQOL were the respective HRQOL scores of the previous year, SLE activity as measured by the Systemic Lupus Activity Questionnaire (SLAQ), and impairments in everyday life. Social support indicated by living in marriage or in a marriage-like partnership had a positive influence on both mental and physical HRQOL, whereas individual factors such as education seemed to be of minor importance. PMID:20829309

  11. Acquired hemophilia A in a patient with systemic lupus erythematosus.

    PubMed

    Ishikawa, T; Tsukamoto, N; Suto, M; Uchiumi, H; Mitsuhashi, H; Yokohama, A; Maesawa, A; Nojima, Y; Naruse, T

    2001-06-01

    A patient with systemic lupus erythematosus (SLE) developed acquired hemophilia A. The patient, a 24-year-old Japanese woman, was referred to our hospital because of uncontrollable bleeding following a tooth extraction. Laboratory examination revealed prolonged APTT (116 seconds), reduced factor VIII activity (2.8 %) and the presence of factor VIII inhibitor at a titer of 46.5 Bethesda units/ml. Transfusion of prothrombin complex concentrate and activated prothrombin complex concentrate followed by administration of prednisolone and cyclophosphamide successfully arrested bleeding and reduced the factor VIII inhibitor level. Acquired hemophilia A is a rare but lethal condition. Rapid diagnosis and introduction of adequate therapies are critical. PMID:11446683

  12. Patient Activation and Mental Health Care Experiences Among Women Veterans.

    PubMed

    Kimerling, Rachel; Pavao, Joanne; Wong, Ava

    2016-07-01

    We utilized a nationally representative survey of women veteran primary care users to examine associations between patient activation and mental health care experiences. A dose-response relationship was observed, with odds of high quality ratings significantly greater at each successive level of patient activation. Higher activation levels were also significantly associated with preference concordant care for gender-related preferences (use of female providers, women-only settings, and women-only groups as often as desired). Results add to the growing literature documenting better health care experiences among more activated patients, and suggest that patient activation may play an important role in promoting engagement with mental health care. PMID:25917224

  13. Patient Activation and Mental Health Care Experiences Among Women Veterans

    PubMed Central

    Pavao, Joanne; Wong, Ava

    2016-01-01

    We utilized a nationally representative survey of women veteran primary care users to examine associations between patient activation and mental health care experiences. A dose–response relationship was observed, with odds of high quality ratings significantly greater at each successive level of patient activation. Higher activation levels were also significantly associated with preference concordant care for gender-related preferences (use of female providers, women-only settings, and women-only groups as often as desired). Results add to the growing literature documenting better health care experiences among more activated patients, and suggest that patient activation may play an important role in promoting engagement with mental health care. PMID:25917224

  14. Dissecting the damage in Northern Greek patients with childhood-onset systemic lupus erythematosus: a retrospective cohort study.

    PubMed

    Koutsonikoli, Artemis; Trachana, Maria; Heidich, Anna-Bettina; Galanopoulou, Vasiliki; Pratsidou-Gertsi, Polyxeni; Garyphallos, Alexandros

    2015-07-01

    The improved survival of childhood-onset systemic lupus erythematosus (cSLE) has resulted in longer patients' exposure to disease inflammation, medications and/or comorbid diseases, which can all contribute to the development of organ damage. The aim of this study was to assess the evolution of damage accrual in cSLE patients overtime and investigate for predisposing factors. Disease characteristics and treatment in 47 Northern Greek Caucasian cSLE patients were retrospectively reviewed. The Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) was used for damage assessment and the European Consensus Lupus Activity Measurement (ECLAM) to monitor cSLE activity. After a median disease duration of 7.4 years, 17/47 patients (36 %) had developed damage (SDI > 0). The most frequent domains damaged were the ocular (41 %), neuropsychiatric (35 %) and peripheral vascular (35 %) one. Peripheral vascular and neuropsychiatric damage was seen more frequently during the first 5 years of the disease. Longer exposure to azathioprine was associated with higher SDI at the end of follow-up (β = 0.008 for every additional month of use, p = 0.041). The mean annual flare frequency was associated with a shorter time interval until the development of the first damage (hazard's ratio, HR 2.38 for each unit of increase, p = 0.018), while hydroxychloroquine use was associated with longer time interval (HR 0.19, p = 0.007). The lower rates of damage accrual in this study compared to other cohorts might be due to milder disease phenotype in Greek Caucasian cSLE patients, prompt diagnosis and effective disease control. Damage was noticed early in the disease course, and one-third of patients had an SDI > 0 at study completion. Disease flares and a severe disease course leading to prolonged use of immunosuppressives were significant risk factors, while hydroxychloroquine use was protective against cSLE damage accrual. PMID

  15. Myth and reality: practical test system for the measurement of anti-DNA antibodies in the diagnosis of systemic lupus erythematosus (SLE).

    PubMed

    McCloskey, Laura J; Christner, Paul; Jacobs-Kosmin, Dana; Jaskowski, Troy D; Hill, Harry R; Lakos, Gabriella; Teodorescu, Marius

    2010-01-01

    The myth persists that only the labor intensive Farr radioimmunoassay and Crithidia luciliae immunofluorescence (CL-IFA) are systemic lupus erythematosus (SLE)-specific tests. We compared them to ELISA with bacteriophage lambda DNA (EL-dsDNA) and denatured calf thymus DNA (EL-ssDNA). By percentile ranking, the specificity cut-off level was set both out of clinical context (SOCC) on 100 blood bank donors, and in clinical context (SICC) on 100 patients with either rheumatoid arthritis or scleroderma (50/50). Clinical sensitivity was calculated on 100 random SLE patients. At 95% SICC, the sensitivity of Farr, CL-IFA, EL-dsDNA, and EL-ssDNA was similar (95%CI): 76% (66-84), 76% (66-84), 63% (53-72), and 75% (65-83), respectively; 87% of the patients were positive by at least one method and 55%by all methods. At 99% SICC, the sensitivity was also similar (95% CI): 57% (47-67), 47% (37-57), 58% (47-67), and 43% (33-53), respectively. The areas under ROC curve were similar (95% CI) when patients were used as controls for specificity. At 99% SOCC, EL-ssDNA identified 89% positive, 2 negative but positive by another method at 95% SICC, and 9 negative (i.e. 89/2/9), followed by CL-IFA (80/6/14), Farr (76/12/12), and EL-dsDNA (64/23/13). Thus, at relatively low cost and easy automation, under the same conditions of specificity, the two ELISA tests combined were at least as good, if not superior, to CL-IFA or Farr: they showed similar clinical sensitivity and also identified more patients with anti-DNA antibodies. PMID:20333761

  16. Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

    PubMed Central

    Schoindre, Yoland; Jallouli, Moez; Tanguy, Marie-Laure; Ghillani, Pascale; Galicier, Lionel; Aumaître, Olivier; Francès, Camille; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Thi Huong, Du Le; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaëlle; Cohen-Bittan, Judith; Hulot, Jean-Sébastien; Lechat, Philippe; Musset, Lucile; Piette, Jean-Charles; Amoura, Zahir; Souberbielle, Jean-Claude; Costedoat-Chalumeau, Nathalie

    2014-01-01

    Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate. PMID:25379192

  17. Changes in referral, treatment and outcomes in patients with systemic lupus erythematosus in Germany in the 1990s and the 2000s

    PubMed Central

    Albrecht, Katinka; Huscher, Dörte; Richter, Jutta; Backhaus, Marina; Bischoff, Sascha; Kötter, Ina; Thiele, Katja; Zink, Angela

    2014-01-01

    Objective To evaluate trends in the referral, treatment and outcome of patients with systemic lupus erythematosus (SLE) in Germany over two decades. Methods From 1993 to 2012, ∼1200 patients with SLE were recorded annually in the national database of the German Collaborative Arthritis Centres. Treatment patterns, healthcare use and outcomes, such as disease activity, function and work participation, were evaluated over time. Furthermore, two distinct cohorts of patients (enrolment 1994–1998, n=467; and 2004–2008, n=376) observed over 5 years were assessed for changes in outcomes. Results The mean disease duration at the first visit to a rheumatologist decreased from 2.6 (1994) to 1.5 (2012) years. Glucocorticoids (69%), antimalarials (56%), azathioprine (22%), non-steroidal anti-inflammatory drugs (23%) and mycophenolate mofetil (15%) were the most frequently used treatments in 2012. A significant increase was observed in the use of antimalarials and mycophenolate mofetil. The use of glucocorticoids at >7.5 mg/day decreased from 27% (1994) to 10% (2012). The average length of sick leave taken due to SLE declined from 9 weeks (1997) to 6 weeks (2012). When comparing the two longitudinal cohorts, in the cohort from the 2000s, the intraindividual decline of disease activity was significantly stronger (p<0.001), and fewer patients retired early (36% vs 46%). Conclusions The disease activity and resource use declined considerably over the observation period, and more patients remained in the labour force. Earlier treatment onset, faster modification of the treatment regimen and more intensive use of anti-inflammatory therapy may account for the improved outcomes in patients with SLE across the years. PMID:25553251

  18. Pyomyositis in a patient with systemic lupus erythaematosus and a review of the literature.

    PubMed

    Meesiri, Somchai

    2016-01-01

    Pyomyositis (PM) is a common masquerading disease that is frequently misdiagnosed. A concurrent state of immunodeficiency is observed in up to 75% of tropical PM cases. PM in systemic lupus erythaematosus (SLE) is a relatively rare disease. I report a case of PM that was caused byKlebsiella pneumoniaein a patient with SLE who presented with leg pain, fever and a lupus flare-up. The patient was correctly diagnosed using a CT scan. Immediate surgical drainage was performed, and empirical antibiotics were administered. The patient was discharged while in a recovering condition. The clinical features, the results of radiographic investigations and the management of PM in SLE are synopsised in this article to underscore the importance of considering this relatively rare disease during differential diagnosis in patients with SLE with muscle pain with or without fever. I also emphasise the need to exclude mycobacterial infection in patients with SLE with PM. PMID:27090546

  19. Cambridge Neuropsychological Test Automated Battery in assessment of cognitive parameters in patients with systemic lupus erythematosus in relation to autoantibody profile

    PubMed Central

    Sobow, Tomasz; Kowalski, Jan; Ząbek, Jakub; Woźniacka, Anna; Bogaczewicz, Jaroslaw

    2015-01-01

    Objectives To relate the cognitive parameters of systemic lupus erythematosus (SLE) patients in remission to their profile of autoantibodies. Material and methods The study included 32 patients with SLE in remission, with mild disease activity as indicated by SELENA-SLEDAI < 6. For neuropsychological assessment, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was applied, using motor screening (MOT), big little circle (BLC), paired associated learning (PAL), stockings of Cambridge (SOC), and graded naming tests (GNT). Detection of autoantibodies against dsDNA, nucleosome (aNuc), Sm, and anticardiolipin (aCL: IgG and IgM) was performed with immunoassays. Results The SLE patients demonstrated standard scores below norms, matched according to age and gender, in the following tests: GNT (–0.87 ±0.85), SOC PSMM (–0.47 ±0.97), PAL (–1.88 ±3.58), and BLC (–0.31 ±1.90). GNT scores under –0.5 were found significantly more frequently in SLE patients, seen in roughly 66% of test subjects. Values for PAL and mean subsequent thinking time of stockings of Cambridge (SOC MSTT) were found to be lower than –0.5 in approximately half of the patients. Mean error of motor screening (MOT ME) was found to negatively correlate with mean latency of motor screening (MOT ML) (r = –0.55). PAL significantly correlated with SOC MSTT (r = 0.38) and with GNT (r = 0.36). Anti-dsDNA antibody level correlated negatively with MOT ME (r = –0.46). Anti-Nuc antibodies correlated with MOT ML (r = 0.41) but negatively correlated with MOT ME (r = –0.58). The levels of anti-Sm, anti-CL IgM and IgG did not correlate significantly with the outcomes of CANTAB. The age of the patients correlated negatively with MOT ME (r = –0.36), positively with BLC (r = 0.53) and negatively with SOC MSTT (r = –0.43). The level of anti-Nuc antibodies correlated with anti-dsDNA level (r = 0.62) and of anti-CL IgM with anti-Sm (r = 0.39) and anti-CL IgG (r = 0.87). Conclusions CANTAB

  20. Morvan Syndrome Secondary to Thymic Carcinoma in a Patient with Systemic Lupus Erythematosus

    PubMed Central

    Koussa, Salam

    2016-01-01

    Morvan syndrome (MoS) is a rare paraneoplastic autoimmune disorder characterized by peripheral nerve hyperexcitability, autonomic dysfunction, and sleep disorders. Systemic lupus erythmatosus (SLE) cooccurs in 6–10% of patients with thymoma. It may occur before, concurrently with, or after thymoma diagnosis. This paper reports the first case of cooccurrence of SLE, thymic carcinoma, and MoS. The cooccurrence of SLE, thymoma, and MoS delineates the generalized autoimmunity process. Symptoms of both MoS and SLE abated upon tumor resection. PMID:27247812

  1. Exploring Patient Activation in the Clinic: Measurement from Three Perspectives

    ERIC Educational Resources Information Center

    Ledford, Christy J. W.; Ledford, Christopher C.; Childress, Marc A.

    2013-01-01

    Objective. To further conceptualize and operationalize patient activation (PA), using measures from patient, physician, and researcher perspectives. Data Source/Study Setting. Multimethod observation in 2010 within a family medicine clinic. Study Design. Part of an intervention with 130 patients with type 2 diabetes, this observational study…

  2. Increasing Patient Activation Could Improve Outcomes for Patients with Inflammatory Bowel Disease.

    PubMed

    Shah, Shawn L; Siegel, Corey A

    2015-12-01

    Inflammatory bowel disease (IBD) is a complex disease process that often requires the integration of skills from various health care providers to adequately meet the needs of patients with IBD. The medical and surgical treatment options for IBD have become more complicated and are frequently a source of angst for both the patient and provider. However, it has become more important than ever to engage patients in navigating the treatment algorithm. Although novel in the IBD world, the concept of patients' becoming more active and effective managers of their care has been well studied in other disease processes such as diabetes mellitus and mental illness. This idea of patient activation refers to a patient understanding his or her role in the care process and having the skill sets and self-reliance necessary to manage his or her own health care. Over the past decade, evidence supporting the role of patient activation in chronic illness has grown, revealing improved health outcomes, enhanced patient experiences, and lower overall costs. Patient activation can be measured, and interventions have been shown to improve levels of activation over time and influence outcomes. A focus on patient activation is very appropriate for patients with IBD because this may potentially serve as a tool for IBD providers to not only improve patient outcomes and experience but also reduce health care costs. PMID:26422517

  3. Sports, Physical Activity and Patient-Reported Outcomes After Medial Unicompartmental Knee Arthroplasty in Young Patients.

    PubMed

    Walker, Tilman; Streit, Julia; Gotterbarm, Tobias; Bruckner, Thomas; Merle, Christian; Streit, Marcus R

    2015-11-01

    One hundred-and-one patients age 60 or younger following medial mobile bearing UKA were reviewed retrospectively with a minimum follow-up of 2 years using the Schulthess activity score, Tegner, UCLA and SF-36 score to assess their level of physical activity and quality of life. Patients showed a rapid recovery and resumption of their activities with a return-to-activity rate of 93%. Most common activities were low impact, whereas high-impact activities showed a significant decrease. Precaution was found to be the main reason for a decrease in the level of activity. The results of this study demonstrate that patients age 60 or younger following medial UKA were able to return to regular physical activities with almost two-thirds of the patients reaching a high activity level (UCLA≥7). PMID:26088397

  4. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  5. High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry

    PubMed Central

    Sun, Celi; Molineros, Julio E.; Looger, Loren L.; Zhou, Xu-jie; Kim, Kwangwoo; Okada, Yukinori; Ma, Jianyang; Qi, Yuan-yuan; Kim-Howard, Xana; Motghare, Prasenjeet; Bhattarai, Krishna; Adler, Adam; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Kochi, Yuta; Suzuki, Akari; Kubo, Michiaki; Sumida, Takayuki; Yamamoto, Kazuhiko; Lee, Shin-Seok; Kim, Young Jin; Han, Bok-Ghee; Dozmorov, Mikhail; Kaufman, Kenneth M.; Wren, Jonathan D.; Harley, John B.; Shen, Nan; Chua, Kek Heng; Zhang, Hong; Bae, Sang-Cheol; Nath, Swapan K.

    2016-01-01

    Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,492 SLE cases and 12,675 controls from six East-Asian cohorts, to identify novel and better localize known SLE susceptibility loci. We identified 10 novel loci as well as 20 known loci with genome-wide significance. Among the novel loci, the most significant was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta=3.75×10−117, OR=2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We localized the most likely functional variants for each locus by analyzing epigenetic marks and gene regulation data. Ten putative variants are known to alter cis- or trans-gene expression. Enrichment analysis highlights the importance of these loci in B- and T-cell biology. Together with previously known loci, the explained heritability of SLE increases to 24%. Novel loci share functional and ontological characteristics with previously reported loci, and are possible drug targets for SLE therapeutics. PMID:26808113

  6. High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.

    PubMed

    Sun, Celi; Molineros, Julio E; Looger, Loren L; Zhou, Xu-Jie; Kim, Kwangwoo; Okada, Yukinori; Ma, Jianyang; Qi, Yuan-Yuan; Kim-Howard, Xana; Motghare, Prasenjeet; Bhattarai, Krishna; Adler, Adam; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Kochi, Yuta; Suzuki, Akari; Kubo, Michiaki; Sumida, Takayuki; Yamamoto, Kazuhiko; Lee, Shin-Seok; Kim, Young Jin; Han, Bok-Ghee; Dozmorov, Mikhail; Kaufman, Kenneth M; Wren, Jonathan D; Harley, John B; Shen, Nan; Chua, Kek Heng; Zhang, Hong; Bae, Sang-Cheol; Nath, Swapan K

    2016-02-24

    Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics. PMID:26808113

  7. Lower paraoxonase 1 activity in Tunisian bipolar I patients

    PubMed Central

    2010-01-01

    Background The purpose of this study was to investigate the variations of paraoxonase activity and lipid profile in bipolar I patients, and the association of this activity with the sociodemographic, clinical and therapeutic characteristics of this population. Patients and methods Our study included 66 patients with bipolar I disorder and 64 controls aged 37.9 ± 12.6 and 36.3 ± 18.2 years, respectively. Paraoxonase activity was determined by kinetic methods; high-density lipoprotein cholesterol (c-HDL), low-density lipoprotein cholesterol (c-LDL), triglycerides and total cholesterol were determined by enzymatic methods; apolipoprotein (Apo)A1, ApoB and lipoprotein (a) (Lp(a)) were determined by immunoturbidimetry using Konelab 30 equipment (Thermo Scientific). Results Compared with controls, patients had a significantly lower paraoxonase activity and ApoA1 level, and significantly higher total cholesterol, c-LDL and Lp(a) level and ApoB/ApoA1 ratio. Furthermore, paraoxonase activity was significantly correlated with c-HDL values (r = 0.5612; P < 0.001). The lowest paraoxonase activity was noted in relation to age and body mass index (BMI). Moreover, it was associated with gender but not with smoking and alcohol consumption status. In patients, there was no significant change in paraoxonase activity in relation to illness episodes, whereas the lowest values of this activity were seen in manic patients. In contrast, paraoxonase activity was significantly associated with treatment. Indeed, patients taking lithium had the lowest levels. Conclusions Bipolar patients had a significant decrease in paraoxonase activity and perturbations in their lipid profile that contribute to increased risk of cardiovascular diseases. Decrease in this activity was significantly associated with treatment with lithium but not with sociodemographic and clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile. PMID:20964824

  8. CCSDS's Cross Support Transfer Services (CSTS) as `Evolution' of SLE Services

    NASA Astrophysics Data System (ADS)

    di Giulio, Margherita

    2015-09-01

    Cross Support Transfer Services (CSTS) are standardized services to allow interoperability between different space agencies for mission cross support. A service user from one agency can use services that are provided from the ground station belonging to another agency. The CCSDS Space Link Extension (SLE) services for delivery of spacecraft telemetry and telecommand between ground stations and control centers are very successful examples for these kinds of services, and have been deployed by almost all space agencies. The CCSDS CSTS Standardization Working Group is about to complete the work on a CCSDS Cross Support Transfer Service Specification Framework. This framework shall facilitate the definition of new cross support services. New services can be composed of already existing or derived procedures and operations. The modular nature of the framework shall also support the implementation of these new services by increasing the options for reusing software components for several services. This paper gives a brief overview of the work of the CCSDS CSTS Standardization Working Group and introduces the concepts of the CSTS Specification Framework and of Services build using such Framework. In order to get any CCSDS recommendation to be published, prototype(s) must be developed, to proof the concepts. This paper will also introduce the prototype developed by the participating Agencies. In particular it will address the ESA-implemented prototype of the Framework (the CSTS Development Kit) based on reuse of the existing SLE API.

  9. Trigger of autoimmune diseases (SLE): identification of LINE transposition based novel therapeutic molecular targets.

    PubMed

    Tiwari, Anupama; Soni, Upendra Kumar

    2014-12-01

    Autoimmune diseases are the highly heterogeneous at cellular and molecular level. The causes and consequences of most of the autoimmune diseases are not well explored. However the researches focusing on the development of biomarkers for the diagnosis of autoimmune diseases are seems to be inadequate and given treatment are insufficient to control or cure the disease properly. It is a big obstacle to develop any therapy without knowing the actual cause and molecular event playing role in disease onset. In this article we are raising the involvement of LINE or other transposition as a first trigger and cause for autoimmune disease. Further we are proposing a novel hybrid aptamers based biocapturing model which would help in the investigation of genome-wide LINE transposition in pristane induced SLE mice model. Importantly the effect of new LINE movements at the expression pattern of neighboring genes would be used as novel molecular prognostic biomarkers for onset of SLE and related autoimmune diseases. We are also proposing that the differential expression either inductive or suppressive pattern of expected several candidate genes would be implicated in the defective biochemical or cellular defects, and targeted therapy would be employed to such life threatening disease. PMID:25468787

  10. Pathogenesis and prevention of rheumatic disease: focus on preclinical RA and SLE

    PubMed Central

    and, Kevin D. Deane; El-Gabalawy, Hani

    2014-01-01

    Established and emerging data demonstrate that a ‘preclinical’ period of disease precedes the onset of clinical rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as other autoimmune rheumatic diseases (ARDs).This preclinical stage of development of disease is characterized by abnormalities in disease-related biomarkers before the onset of the clinically apparent signs and symptoms. Numerous genetic and environmental risk factors for ARDs have also been identified, and many of these factors are likely to act before the clinical appearance of tissue injury to initiate and/or propagate autoimmunity and autoimmune disease. Thus, biomarkers representative of these autoimmune processes could potentially be used in conjunction with other clinical parameters during the preclinical period of ARDs to predict the future development of clinically apparent disease. This Review focuses on the preclinical stages of RA and SLE, as our current understanding of these diseases can be used to present an overall model of the development of ARDs that might ultimately be used to develop screening programmes and preventive strategies. Important considerations for the future development of such approaches, in particular, the issues that require additional research and how they might be addressed, are also discussed. PMID:24514912

  11. Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

    PubMed Central

    Yamada, Masanori; Akita, Mikio; Nakagawa, Tomofumi; Takahashi, Naoki; Endo, Akira; Yoshida, Pascal

    2013-01-01

    Objectives Belimumab, an anti-B lymphocyte stimulator (BLyS) human monoclonal antibody, was approved in the United States, Canada and European Union for the treatment of the patients with systemic lupus erythematosus (SLE). However, belimumab had not been evaluated in Japanese patients. The objectives of this study were to evaluate the safety and tolerability of belimumab in Japanese patients with SLE, as well as to investigate the pharmacokinetics (PK) and biological activity of belimumab in this population. Methods A total of 12 Japanese patients were enrolled in a randomized, single-blind, placebo-controlled, dose-ascending design study. A dosing regimen of a single intravenous infusion over 1 hour of belimumab (1 mg/kg and 10 mg/kg) was employed. Patients were followed for 84 days after dosing to assess adverse events, pharmacokinetics, biomarkers and SLE disease activity. Clinical trial registration number ClinicalTrials.gov identifier is NCT01381536. Results Belimumab (1 mg/kg and 10 mg/kg) demonstrated a favorable clinical safety and tolerability profile in Japanese patients with SLE. The incidence of adverse events was similar among the two belimumab groups and placebo group. The PK profile of single-dose belimumab was approximately dose proportional, and the long terminal elimination half-life (12.4–15.7 days), low clearance (3.55–4.65 mL/day/kg), and small volume of distribution (76.2–80.1 mL/kg) were consistent with a fully humanized antibody. Effects of belimumab on B cells suggested biological activity effects expected as an inhibitor of BLyS. Limitation The small sample size and single dose design of this study prevent definitive conclusions regarding the safety, pharmacokinetics or pharmacodynamics of belimumab in a Japanese population being made. Conclusions The preliminary safety, PK profile, and observed biological activity of belimumab support further evaluation of its safety and efficacy in Japanese patient with SLE.

  12. Circulating thymic hormone activity in young cancer patients.

    PubMed Central

    Consolini, R; Cei, B; Cini, P; Bottone, E; Casarosa, L

    1986-01-01

    We measured serum levels of Facteur Thymique Sérique (FTS) in 56 young cancer patients compared to normal controls. All patients who received immunosuppressive therapy had low age-corrected titres of FTS. Low levels were also found at diagnosis and off therapy. Plasma from 22 patients contained factors capable of inhibiting biological activity of FTS in vitro. The nature of this inhibitor has not been elucidated. No zinc deficiency was found in the patients studied, suggesting that FTS is secreted in its active form. Our study points out the importance of monitoring FTS activity in young cancer patients for its implications on immunological surveillance. The practical applications of thymic hormone therapy in cancer patients are discussed. PMID:3802571

  13. Sexual activity among patients in psychiatric hospital wards.

    PubMed

    Warner, James; Pitts, Nicola; Crawford, Mike J; Serfaty, Marc; Prabhakaran, Pramod; Amin, Rizkar

    2004-10-01

    In psychiatric hospitals, sexual activity between patients raises special difficulties regarding consent. We undertook a questionnaire survey of inpatients in the mental health units of three hospitals to identify the nature and frequency of sexual activity. A contemporaneous staff questionnaire was used in an attempt to validate the patient reports. Of the 100 patients who participated (response rate 60%), 30 reported engaging in some form of sexual activity including 10 who had sexual intercourse. All sexual intercourse was consensual, but only 2 respondents used condoms. Staff questionnaires suggested levels of sexual activity congruent with patient reports. This survey underlines the conflict between an individual's right to sexual expression and the need to protect vulnerable patients. PMID:15459258

  14. Copy Number Variation of TLR-7 Gene and its Association with the Development of Systemic Lupus Erythematosus in Female Patients from Yucatan Mexico

    PubMed Central

    Pacheco, Guillermo Valencia; Cruz, Darig Cámara; González Herrera, Lizbeth J; Pérez Mendoza, Gerardo J; Adrián Amaro, Guadalupe I; Nakazawa Ueji, Yumi E; Angulo Ramírez, Angélica V

    2014-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies against self-antigens, which occurs most often in women between 15 and 40 years of age. The innate immunity is involved in the pathogenesis of SLE through TLR- 7. Genetic factors such as copy number variation (CNV) of target genes may contribute to disease development, but this possible risk has not yet been studied in SLE patients from Yucatan, Mexico. The CNV of TLR-7 gene was determined by quantitative polymerase chain reaction assay using TaqMan probes in 80 SLE women and 150 control subjects. The results showed that 10% of SLE patients exhibited more than two copies of TLR-7 gene, whereas no mRNA overexpression was detected. These data suggested that increased CNV of the TLR-7 gene in Yucatan SLE women can be a risk factor for this disease. PMID:25512712

  15. Intestinal pseudo-obstruction in patients with systemic lupus erythematosus: a real diagnostic challenge.

    PubMed

    García López, Carlos Alberto; Laredo-Sánchez, Fernando; Malagón-Rangel, José; Flores-Padilla, Miguel G; Nellen-Hummel, Haiko

    2014-08-28

    Intestinal pseudo-obstruction secondary to systemic lupus erythematosus (SLE) is a rare syndrome described in recent decades. There are slightly over 30 published cases in the English language literature, primarily associated with renal and hematological disease activity. Its presentation and evolution are a diagnostic challenge for the clinician. We present four cases of intestinal pseudo-obstruction due to lupus in young Mexican females. One patient had a previous diagnosis of SLE and all presented with a urinary tract infection of varying degrees of severity during their evolution. We consider that recognition of the disease is of vital importance because it allows for establishing appropriate management, leading to a better prognosis and avoiding unnecessary surgery and complications. PMID:25170234

  16. Hair dye treatment use and clinical course in patients with systemic lupus erythematosus and cutaneous lupus.

    PubMed

    Jiménez-Alonso, J; Sabio, J M; Pérez-Alvarez, F; Reche, I; Hidalgo, C; Jáimez, L

    2002-01-01

    The etiological role of hair dye treatment (HDT), some of them such as permanent hair dyes containing aromatic amines, in the development of SLE has been previously ruled out. However, the possible influence of HDT use on the course and prognosis of lupus patients has been assessed only in one short-term study. Since HDT is very extensive among the population, the knowledge of this possible negative effect may be very important. Thus, the aim of this study was to assess the long-term influence of several HDTs on the course and clinical severity of patients with both systemic lupus erythematosus (SLE) and cutaneous lupus (CL). In this longitudinal case series study, 91 SLE patients and 22 CL patients were prospectively studied from October 1988 to May 2000. They were divided into three groups: (a) non-HDT users--patients who have never used HDT (n = 65); (b) P-HDT users--HDT permanent type users, alone or in combination with other types of HDT (n = 28); (c) non P-HDT--users of other treatments different from permanent tinting (bleach, lowlights, etc; n = 20). In each patient we determined: (1) number of flares/year in SLE patients and worsening of cutaneous lesions for CL; (2) Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index; (3) predominant damaged organs/systems according to the HDT use and type of HDT; and (4) subjective impression about the disease evolution in relation to HDT use. No significant differences were found with respect to flares/year and SLICC/ACR damage index between the study groups. Non-HDT group presented more renal involvement and serositis than both HDT-user groups. No patient related the HDT use to the worsening of his disease. Therefore, in this study no evidence of an association between the long-term use of several types of HDT and the clinical activity and course of SLE and CL was found. PMID:12195784

  17. Recommendations for physical activity in patients with multiple sclerosis.

    PubMed

    Petajan, J H; White, A T

    1999-03-01

    For many years, patients with multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system, have been advised to avoid exercise. MS is believed to be autoimmune in origin, mediated by activated T cells which penetrate the blood-brain barrier and attack myelin. The pathophysiology, with respect to function is an impairment of saltatory conduction, specifically, slowing of conduction speed and/or conduction block. Symptoms can temporarily worsen on exposure to heat or during physical exercise. Exercise programmes must be designed to activate working muscles but avoid overload that results in conduction block. Fatigue, often severe, affects about 85% of MS patients and, along with motor and sensory symptoms, results in decreased mobility and reduced quality of life. Physical activity and recreation are reduced in patients with MS. Before developing recommendations, physical activity patterns and the physical effects of MS should be assessed in individual patients. Patients may then be functionally classified. Physical activity can also be classified in a pyramid structure, with the most basic functions forming the base and the most integrated functions on top. The muscular fitness pyramid progresses through passive range of motion, active resistive, specific strengthening and integrated strength exercises Overall physical activity may be increased according to functional level by performing activities of daily living, incorporating inefficiencies into daily living, pursuing more active recreation and eventually developing a structured exercise programme. The importance of the proper exercise environment, balance and coordination issues and factors related to adherence are discussed. PMID:10222541

  18. Plasma thymic hormone activity in patients with chronic mucocutaneous candidiasis

    PubMed Central

    Kirkpatrick, C. H.; Greenberg, Lynn E.; Chapman, S. W.; Goldstein, G.; Lewis, Verna M.; Twomey, J. J.

    1978-01-01

    To further characterize the immunological abnormalities in patients with chronic mucocutaneous candidiasis, the thymic hormone activity in their plasma was measured. Of the sixteen patients in the study, seven had chronic diffuse candidiasis, five had candidiasis with endocrinopathies and four had candidiasis with thymoma. Only one patient, an anergic child with chronic diffuse candidiasis had severe deficiency of plasma thymic hormone activity. Two patients, a woman with candidiasis and multiple endocrinopathies and an elderly man with metastatic epithelial thymoma had supranormal values. These studies indicate that the immunological deficit in most patients with these forms of chronic mucocutaneous candidiasis is not due to deficiency of a thymic inductive activity and suggest that an intrinsic defect exists in the maturation of antigen-responsive lymphoid cells. PMID:743805

  19. Psychometric validation of the Brief Pain Inventory-Short Form in patients with systemic lupus erythematosus in the United States.

    PubMed

    Naegeli, A N; Tomaszewski, E L; Al Sawah, S

    2015-11-01

    This study evaluated the Brief Pain Inventory-Short Form (BPI-SF) in patients with moderate-to-severe systemic lupus erythematosus (SLE). Patients ≥18 years old who self-reported a physician diagnosis of SLE (confirmed by medical record review) and active SLE (Systemic Lupus Activity Questionnaire (SLAQ) score of ≥11) were included. The BPI-SF and Short Form Health Survey version 2 (SF-36v2) were administered electronically at baseline, week 2 and week 12. Psychometric properties of the BPI-SF were evaluated. Cronbach alphas were >0.9 for all BPI-SF items, domains and total score. Test-retest reliability correlations for responses between baseline and week 2 of the BPI-SF had intraclass correlation coefficients (ICCs) ≥0.5. The BPI-SF domains and total score were moderately positively correlated to the SLAQ score (r ≥ 0.4), but negatively correlated to the SF-36v2 bodily pain domain (r ≤ -0.6). The BPI-SF domains and total score were moderately negatively correlated to the SF-36v2 physical functioning domain and physical component summary (r ≤ -0.4), with low correlations between the BPI-SF severity domain and SF-36v2 mental component summary (r = -0.16). Assessment of pain, as measured by the BPI-SF, demonstrated validity and reliability in a sample of patients with moderate-to-severe SLE. PMID:26038345

  20. Inadvertant hypothermia and active warming for surgical patients.

    PubMed

    Tanner, Judith

    Inadvertant hypothermia is common among surgical patients and can result in serious complications. This article describes active warming systems which can be used preoperatively and intraoperatively to prevent hypothermia and maintain normothermia (normal body temperature). PMID:22067488

  1. Variables associated with patient activation in persons with multiple sclerosis.

    PubMed

    Goodworth, Marie-Christine R; Stepleman, Lara; Hibbard, Judith; Johns, Lisa; Wright, Dustin; Hughes, Mary D; Williams, Mitzi J

    2016-01-01

    Identifying variables associated with patient activation in the multiple sclerosis population could serve to facilitate better multiple sclerosis self-management behaviors. Using a cross-sectional survey design, 199 participants were recruited from a multiple sclerosis center in the Southeastern United States. Depression, multiple sclerosis quality of life, and multiple Sclerosis self-efficacy were all significantly correlated with patient activation. Results of a hierarchical regression indicated that patient activation was significantly related to educational attainment, depression, and self-efficacy but not to quality of life. The results suggest several possible targets for intervention to increase patient activation, including health literacy, depression symptoms, and self-efficacy for multiple sclerosis disease management. PMID:24591120

  2. Differential clearance mechanisms, neutrophil extracellular trap degradation and phagocytosis, are operative in systemic lupus erythematosus patients with distinct autoantibody specificities.

    PubMed

    Chauhan, Sudhir Kumar; Rai, Richa; Singh, Vikas Vikram; Rai, Madhukar; Rai, Geeta

    2015-12-01

    Systemic lupus erythematosus (SLE) patients are generally presented with autoantibodies against either dsDNA or RNA-associated antigens (also known as extractable nuclear antigens, ENA) or both. However, the mechanisms and processes that lead to this distinctive autoantibody profile are not well understood. Defects in clearance mechanism i.e. phagocytosis may lead to enhanced microbial and cellular debris of immunogenic potential. In addition to defective phagocytosis, impaired neutrophil extracellular trap (NET) degradation has been recently reported in SLE patients. However, the extent to which both these clearance processes (NET-degradation and phagocytosis) are operative in serologically distinguished subsets of SLE patients is not established. Therefore, in this report, we evaluated NET-degradation and phagocytosis efficiency among SLE patients with different autoantibody specificities. SLE patients were classified into three subsets based on their autoantibody profile (anti-dsDNA, anti-ENA or both) as determined by ELISA. NET-degradation by SLE and control sera was assessed by sytox orange-based fluorescence assay. Neutrophil-mediated phagocytosis in the presence of SLE and control sera was determined by flowcytometry. The segregation of SLE patients revealed significant differences in NET-degradation and phagocytosis in SLE patients with autoantibodies against dsDNA and ENA. We report that NET-degradation efficiency was significantly impaired in SLE patients with anti-dsDNA autoantibodies and not in those with anti-ENA autoantibodies. In contrast to NET-degradation, neutrophil-mediated phagocytosis was impaired in all three subsets independent of autoantibody specificity. These observations suggest that varying clearance mechanisms are operative in SLE subsets with anti-dsDNA or anti-ENA autoantibodies. The results outlined in this manuscript also suggest that sub-grouping of SLE patients could be useful in delineating the molecular and pathological

  3. Management of Hypertension: Adapting New Guidelines for Active Patients.

    ERIC Educational Resources Information Center

    Tanji, Jeffrey L.; Batt, Mark E.

    1995-01-01

    Discusses recent guidelines on hypertension from the National Heart, Lung, and Blood Institute and details the latest management protocols for patients with high blood pressure. The article helps physicians interpret the guidelines for treating active patients, highlighting diagnosis, step care revision, pharmacology, and sports participation…

  4. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder

    PubMed Central

    Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-01-01

    Objective Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. Methods The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Results Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (p<0.01). Conclusion The findings of the present study suggest that the decrease in prolidase activity may have neuroprotective effects in patients with PTSD. PMID:27482243

  5. A pathogenic IFNα, BLyS and IL-17 axis in Systemic Lupus Erythematosus patients

    PubMed Central

    López, Patricia; Rodríguez-Carrio, Javier; Caminal-Montero, Luis; Mozo, Lourdes; Suárez, Ana

    2016-01-01

    This study aims to analyze in depth the role of IFNα in the upregulation of BLyS in different leukocyte populations and the possible relationship of these molecules with IL-17 and other pathogenic cytokines in SLE. Thus, IFNAR1 and membrane BLyS (mBLyS) expression was upregulated on various blood cell types from patients and closely correlated in all individuals. Moreover, BLyS serum levels associated positively with IFNα and IL-17A amounts, as well as with mBLyS on B cells and neutrophils. Interestingly, mBLyS on neutrophils was also correlated with IL-17A levels. Additionally, intracellular IL-17A expression was increased in both CD4+ lymphocytes and neutrophils from patients, and IL-17+CD4+ T cell frequency was associated with serum IFNα and IFNRA1 expression on B cells. Finally, in vitro assays support an IFNα role in the activation of Th17 cells in SLE. In conclusion, these data suggest that IFNα, BLyS and IL-17 could form a pathological axis in SLE, involving T and B lymphocytes, monocytes, DCs and neutrophils, which act in a vicious circle that encourage the preexisting inflammation and propagate the disease process. PMID:26847824

  6. Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus.

    PubMed

    Koh, J H; Ko, H S; Kwok, S-K; Ju, J H; Park, S-H

    2015-02-01

    We investigated the clinical and laboratory characteristics of pregnancies with systemic lupus erythematosus (SLE) and identified lupus flare predictors during pregnancy. Additionally, we examined lupus activity and pregnancy outcomes in SLE patients who continued, discontinued or underwent no hydroxychloroquine (HCQ) treatment during pregnancy. We retrospectively analyzed 179 pregnancies in 128 SLE patients at Seoul St. Mary's Hospital, Korea, between 1998 and 2012 and then assessed the clinical profiles and maternal and fetal outcomes. Overall, 90.5% of pregnancies resulted in a successful delivery and were divided into two groups: those who experienced lupus flares (80 pregnancies, 44.7%) and those who did not (99 pregnancies, 55.3%). Increased preeclampsia, preterm births, low birth weight, intrauterine growth restriction (IUGR), and low 1-minute Apgar scores occurred in pregnancies with lupus flares compared to pregnancies in quiescent disease. Lupus flares were predicted by HCQ discontinuation, a history of lupus nephritis, high pre-pregnancy serum uric acid and low C4 levels. Our study indicates that achieving pre-pregnancy remission and continuing HCQ treatment during pregnancy are important for preventing lupus flares. PMID:25305214

  7. 9G4 Autoreactivity Is Increased in HIV-Infected Patients and Correlates with HIV Broadly Neutralizing Serum Activity

    PubMed Central

    Kobie, James J.; Alcena, Danielle C.; Zheng, Bo; Bryk, Peter; Mattiacio, Jonelle L.; Brewer, Matthew; LaBranche, Celia; Young, Faith M.; Dewhurst, Stephen; Montefiori, David C.; Rosenberg, Alexander F.; Feng, Changyong; Jin, Xia; Keefer, Michael C.; Sanz, Ignacio

    2012-01-01

    The induction of a broadly neutralizing antibody (BNAb) response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infected patients do develop circulating BNAbs, from which several potent broadly neutralizing monoclonal antibodies (mAbs) have been isolated. The findings that several BNmAbs exhibit autoreactivity and that autoreactive serum antibodies are observed in some HIV patients have advanced the possibility that enforcement of self-tolerance may contribute to the rarity of BNAbs. To examine the possible breakdown of tolerance in HIV patients, we utilized the 9G4 anti-idiotype antibody system, enabling resolution of both autoreactive VH4-34 gene-expressing B cells and serum antibodies. Compared with healthy controls, HIV patients had significantly elevated 9G4+ serum IgG antibody concentrations and frequencies of 9G4+ B cells, a finding characteristic of systemic lupus erythematosus (SLE) patients, both of which positively correlated with HIV viral load. Compared to the global 9G4−IgD− memory B cell population, the 9G4+IgD− memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward “IgM only" memory. HIV envelope reactivity was observed both in the 9G4+ serum antibody and 9G4+ B cell population. 9G4+ IgG serum antibody levels positively correlated (r = 0.403, p = 0.0019) with the serum HIV BNAbs. Interestingly, other serum autoantibodies commonly found in SLE (anti-dsDNA, ANA, anti-CL) did not correlate with serum HIV BNAbs. 9G4-associated autoreactivity is preferentially expanded in chronic HIV infection as compared to other SLE autoreactivities. Therefore, the 9G4 system provides an effective tool to examine autoreactivity in HIV patients. Our results suggest that the development of HIV BNAbs is not merely a consequence of a general breakdown in

  8. The spectrum of nasal involvement in systemic lupus erythematosus and its association with the disease activity.

    PubMed

    Kusyairi, K A; Gendeh, B S; Sakthiswary, R; Shaharir, S S; Haizlene, A H; Yusof, K H

    2016-04-01

    The purpose of this study was to determine the spectrum of nasal involvement in systemic lupus erythematosus (SLE) and its association with the disease activity of SLE based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This was a cross-sectional and observational study involving 73 stable SLE patients. All subjects were evaluated for the SLEDAI scores and had nasal endoscopic examination. The most commonly reported symptom was nasal congestion (31.5%) followed by nasal itchiness (26.0%), runny nose (20.5%) and nasal dryness (19.2%). Almost half (42.9%) of the subjects had nasal mucosal abnormalities, which included mucositis, crusting, ulceration, bifid middle turbinate, septal spur, Jacobson's organ, deviated nasal septum, bilateral inferior turbinate hypertrophy, everted uncinate process, nasopharynx cleft and torus palatinus. The median SLEDAI score for subjects with nasal symptoms was significantly higher than subjects without nasal symptoms (p < 0.05). Similarly, subjects with moderate to high activity (SLEDAI scores of 6-19) had a significantly higher frequency of both nasal symptoms and nasal mucosal abnormalities (p < 0.05) compared to subjects with no to mild activity (SLEDAI scores of 0-5). PMID:26657735

  9. Complement Activation in Patients with Focal Segmental Glomerulosclerosis

    PubMed Central

    Thurman, Joshua M.; Wong, Maria; Renner, Brandon; Frazer-Abel, Ashley; Giclas, Patricia C.; Joy, Melanie S.; Jalal, Diana; Radeva, Milena K.; Gassman, Jennifer; Gipson, Debbie S.; Kaskel, Frederick; Friedman, Aaron; Trachtman, Howard

    2015-01-01

    Background Recent pre-clinical studies have shown that complement activation contributes to glomerular and tubular injury in experimental FSGS. Although complement proteins are detected in the glomeruli of some patients with FSGS, it is not known whether this is due to complement activation or whether the proteins are simply trapped in sclerotic glomeruli. We measured complement activation fragments in the plasma and urine of patients with primary FSGS to determine whether complement activation is part of the disease process. Study Design Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed. Setting and Participants We identified 19 patients for whom samples were available from weeks 0, 26, 52 and 78. The results for these FSGS patients were compared to results in samples from 10 healthy controls, 10 patients with chronic kidney disease (CKD), 20 patients with vasculitis, and 23 patients with lupus nephritis. Outcomes Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR). Measurements Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine. Results Plasma and urine Ba, C4a, sC5b-9 were significantly higher in FSGS patients at the time of diagnosis than in the control groups. Plasma Ba levels inversely correlated with the eGFR at the time of diagnosis and at the end of the study. Plasma and urine Ba levels at the end of the study positively correlated with the level of proteinuria, the primary outcome of the study. Limitations Limited number of patients with samples from all time-points. Conclusions The complement system is activated in patients with primary FSGS, and elevated levels of plasma Ba correlate with more severe disease. Measurement of complement fragments may identify a subset of patients in whom the complement system is activated. Further investigations are needed to confirm our findings and to determine the prognostic significance of

  10. Synchronization of EEG activity in patients with bipolar disorder

    NASA Astrophysics Data System (ADS)

    Panischev, O. Yu; Demin, S. A.; Muhametshin, I. G.; Demina, N. Yu

    2015-12-01

    In paper we apply the method based on the Flicker-Noise Spectroscopy (FNS) to determine the differences in frequency-phase synchronization of the cortical electroencephalographic (EEG) activities in patients with bipolar disorder (BD). We found that for healthy subjects the frequency-phase synchronization of EEGs from long-range electrodes was significantly better for BD patients. In BD patients a high synchronization of EEGs was observed only for short-range electrodes. Thus, the FNS is a simple graphical method for qualitative analysis can be applied to identify the synchronization effects in EEG activity and, probably, may be used for the diagnosis of this syndrome.

  11. Altered AKT1 and MAPK1 Gene Expression on Peripheral Blood Mononuclear Cells and Correlation with T-Helper-Transcription Factors in Systemic Lupus Erythematosus Patients

    PubMed Central

    Garcia-Rodriguez, Sonia; Callejas-Rubio, Jose-Luis; Ortego-Centeno, Norberto; Zumaquero, Esther; Ríos-Fernandez, Raquel; Arias-Santiago, Salvador; Navarro, Pilar; Sancho, Jaime; Zubiaur, Mercedes

    2012-01-01

    Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE). v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1) and mitogen-activated-protein-kinase 1 (MAPK1) gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th) transcription factors (TF) gene expression, cytokines, and S100A8/S100A9-(Calprotectin). Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR)-C), T-regulatory-(Treg)-(Transforming Growth Factor Beta (TGFB)-2), and Th2-(interleukin (IL)-5)-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet)), Th2-(GATA binding protein-(GATA)-3), and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF)-α and Th0-(IL-2), Th1-(IL-12A, T-bet), GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP)-3), and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1β, IL-12(p70), Interferon-(IFN)-γ, and IL-6 cytokines were augmented. Plasma IL-1β, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity. PMID:23125486

  12. Management of patients with active caries.

    PubMed

    Milgrom, Peter

    2014-07-01

    This paper reports on a mechanism to manage caries as a disease and to medically intervene in the disease process to halt progression. The goal of this paper is to provide this alternative to a surgical-only approach. The management of caries begins with assessing lesion activity and the potential for arrest. This requires a clinical and radiological assessment and evaluation of risk. Hopeless teeth are extracted and large cavities filled to reduce infection. Risk reduction strategies are employed so efforts to arrest lesions can be successful. Teeth with lesions in the enamel or outer third of the dentin should be sealed, not restored, as restorations can weaken teeth and can be traumatic to pulps. PMID:25076627

  13. A multi-center, cross-sectional study on quality of life in cutaneous lupus erythematosus patients

    PubMed Central

    Vasquez, R.; Wang, D.; Tran, Q.P.; Adams-Huet, B.; Chren, M.-M.; Costner, M.I.; Cohen, J.B.; Werth, V.P.; Chong, B.F.

    2012-01-01

    Background A study at the University of Pennsylvania (UPenn) Medical Center demonstrated that quality of life in cutaneous lupus erythematosus (CLE) patients is negatively impacted. Whether CLE patients in other geographic locations have similar quality of life is unknown. Objective We sought to compare quality of life indicators between CLE patients at the University of Texas Southwestern (UTSW) Medical Center at Dallas and UPenn. Methods 248 CLE patients at UTSW (N=91) and UPenn (N=157) completed the Skindex-29+3 and Short Form-36 (SF-36) surveys related to quality of life. Additional information including demographics, presence of SLE, and disease severity were collected from UTSW CLE patients. Results Most Skindex-29+3 and SF-36 sub-domain scores between UTSW and UPenn CLE patients were similar. However, UTSW CLE patients were significantly more affected in the functioning and lupus-specific Skindex-29+3 domains, and physical functioning, role-physical, and general health SF-36 subscales than UPenn CLE patients (p<0.05). Factors related to poor quality of life in UTSW CLE patients include gender, income, education, presence of SLE, and skin disease activity. Conclusions Most quality of life indicators were similar between the two CLE populations. Differences in psychosocial behavior, and a larger proportion of SLE patients and females in the UTSW group likely attributed to differences in a minority of Skindex-29+3 and SF-36 sub-domains. Capturing data from CLE populations in different locations provides a more thorough picture of the quality of life that CLE patients experience on a daily basis with special attention to quality of life issues in select CLE patients. PMID:22708924

  14. Physical Activity in Hemodialysis Patients Measured by Triaxial Accelerometer

    PubMed Central

    Gomes, Edimar Pedrosa; Reboredo, Maycon Moura; Carvalho, Erich Vidal; Teixeira, Daniel Rodrigues; Carvalho, Laís Fernanda Caldi d'Ornellas; Filho, Gilberto Francisco Ferreira; de Oliveira, Julio César Abreu; Sanders-Pinheiro, Helady; Chebli, Júlio Maria Fonseca; de Paula, Rogério Baumgratz; Pinheiro, Bruno do Valle

    2015-01-01

    Different factors can contribute to a sedentary lifestyle among hemodialysis (HD) patients, including the period they spend on dialysis. The aim of this study was to evaluate characteristics of physical activities in daily life in this population by using an accurate triaxial accelerometer and to correlate these characteristics with physiological variables. Nineteen HD patients were evaluated using the DynaPort accelerometer and compared to nineteen control individuals, regarding the time spent in different activities and positions of daily life and the number of steps taken. HD patients were more sedentary than control individuals, spending less time walking or standing and spending more time lying down. The sedentary behavior was more pronounced on dialysis days. According to the number of steps taken per day, 47.4% of hemodialysis patients were classified as sedentary against 10.5% in control group. Hemoglobin level, lower extremity muscle strength, and physical functioning of SF-36 questionnaire correlated significantly with the walking time and active time. Looking accurately at the patterns of activity in daily life, HDs patients are more sedentary, especially on dialysis days. These patients should be motivated to enhance the physical activity. PMID:26090432

  15. Physical Activity in Hemodialysis Patients Measured by Triaxial Accelerometer.

    PubMed

    Gomes, Edimar Pedrosa; Reboredo, Maycon Moura; Carvalho, Erich Vidal; Teixeira, Daniel Rodrigues; Carvalho, Laís Fernanda Caldi d'Ornellas; Filho, Gilberto Francisco Ferreira; de Oliveira, Julio César Abreu; Sanders-Pinheiro, Helady; Chebli, Júlio Maria Fonseca; de Paula, Rogério Baumgratz; Pinheiro, Bruno do Valle

    2015-01-01

    Different factors can contribute to a sedentary lifestyle among hemodialysis (HD) patients, including the period they spend on dialysis. The aim of this study was to evaluate characteristics of physical activities in daily life in this population by using an accurate triaxial accelerometer and to correlate these characteristics with physiological variables. Nineteen HD patients were evaluated using the DynaPort accelerometer and compared to nineteen control individuals, regarding the time spent in different activities and positions of daily life and the number of steps taken. HD patients were more sedentary than control individuals, spending less time walking or standing and spending more time lying down. The sedentary behavior was more pronounced on dialysis days. According to the number of steps taken per day, 47.4% of hemodialysis patients were classified as sedentary against 10.5% in control group. Hemoglobin level, lower extremity muscle strength, and physical functioning of SF-36 questionnaire correlated significantly with the walking time and active time. Looking accurately at the patterns of activity in daily life, HDs patients are more sedentary, especially on dialysis days. These patients should be motivated to enhance the physical activity. PMID:26090432

  16. Aberration of monokine production and monocyte subset in patients with systemic lupus erythematosus.

    PubMed

    Takei, M; Kang, H; Tomura, K; Amaki, S; Hirata, M; Karasaki, M; Sawada, S; Amaki, I

    1987-04-01

    We measured the production of interleukin 1 (IL-1) and prostaglandin by adherent cells from patients with systemic lupus erythematosus (SLE). Compared to normal subjects, IL-1 production in the patients was lower but prostaglandin E1 production was higher. Furthermore, examination of monocyte subsets in patients with SLE using monoclonal anti-monocyte/granulocyte antibodies disclosed abnormal expression of membrane antigens on monocytes. It is speculated that aberration of monocyte function is related to impaired monokine production and that membrane antigens play a role in immunodysregulation in patients with SLE. PMID:3497275

  17. [Creative arts activity in manually handicapped patients].

    PubMed

    Wolf, N

    1986-02-01

    Congenital or acquired conditions directly or indirectly causal in total or partial impairment of manual function are set out. The possibilities for creative-expressive activity, using various techniques, nothwithstanding manual disabilities are pointed out. In Cefischer, who until his war-related loss of both upper limbs had been a renowned cartoonist, a comparison of his works, drawn initially by hand and later with the mouth, reveals his characteristic style of expression having remained the same. Further examples are given of creative expression in the presence of manual disability even under extreme circumstances (such as 11 years of confinement to the Iron Lung). Arts and crafts work of persons with leprosy-related manual handicaps are mentioned; typewriter graphics as a method inaugurated by Basset is presented as used in young people with total manual disability. Partial disability of manual function due to arthritis was present in Renoir, Jawlensky, and Grandma Moses, the course of their conditions is described over time. Contents and form of their pictures, after long years of being manually disabled, do not reveal any essential changes in comparison to their earlier ones. PMID:2938233

  18. Early Vascular Aging in Normotensive Patients With Systemic Lupus Erythematosus: Comparison With Young Patients Having Hypertension.

    PubMed

    Morreale, Massimiliano; Mulè, Giuseppe; Ferrante, Angelo; D'ignoto, Francesco; Cottone, Santina

    2016-08-01

    Connective tissue diseases, like systemic lupus erythematosus (SLE), are associated with early and accelerated atherosclerosis. Recently, the concept of "early vascular aging" (EVA) has been more widely accepted. Aortic stiffness is one of the important markers of EVA. We evaluated EVA and subclinical atherosclerosis, by measuring aortic pulse wave velocity (aPWV) and carotid intima-media thickness (cIMT), in 50 normotensive patients with SLE (mean age: 39 ± 12 years). We compared these participants with 50 age- and sex-matched patients with essential hypertension (EH) and 20 healthy controls. Each participant underwent 24-hour ambulatory blood pressure monitoring (ABPM), aPWV, and cIMT measurements. Clinic and 24-hour ABPM values were significantly lower in patients with SLE and controls when compared with the participants having EH (all P < .0001), but aPWV and cIMT were significantly lower in the control group when compared with patients having SLE and EH (all P < .001). Overall, patients with SLE and EH had similar cIMT and aPWV values (P = .31 and P = .47, respectively). Our results suggest that SLE has a similar deleterious impact on EVA as EH. PMID:26535012

  19. The germination-specific lytic enzymes SleB, CwlJ1, and CwlJ2 each contribute to Bacillus anthracis spore germination and virulence.

    PubMed

    Giebel, Jonathan D; Carr, Katherine A; Anderson, Erica C; Hanna, Philip C

    2009-09-01

    The bacterial spore cortex is critical for spore stability and dormancy and must be hydrolyzed by germination-specific lytic enzymes (GSLEs), which allows complete germination and vegetative cell outgrowth. We created in-frame deletions of three genes that encode GSLEs that have been shown to be active in Bacillus anthracis germination: sleB, cwlJ1, and cwlJ2. Phenotypic analysis of individual null mutations showed that the removal of any one of these genes was not sufficient to disrupt spore germination in nutrient-rich media. This finding indicates that these genes have partially redundant functions. Double and triple deletions of these genes resulted in more significant defects. Although a small subset of DeltasleB DeltacwlJ1 spores germinate with wild-type kinetics, for the overall population there is a 3-order-of-magnitude decrease in the colony-forming efficiency compared with wild-type spores. DeltasleB DeltacwlJ1 DeltacwlJ2 spores are unable to complete germination in nutrient-rich conditions in vitro. Both DeltasleB DeltacwlJ1 and DeltasleB DeltacwlJ1 DeltacwlJ2 spores are significantly attenuated, but are not completely devoid of virulence, in a mouse model of inhalation anthrax. Although unable to germinate in standard nutrient-rich media, spores lacking SleB, CwlJ1, and CwlJ2 are able to germinate in whole blood and serum in vitro, which may explain the persistent low levels of virulence observed in mouse infections. This work contributes to our understanding of GSLE activation and function during germination. This information may result in identification of useful therapeutic targets for the disease anthrax, as well as provide insights into ways to induce the breakdown of the protective cortex layer, facilitating easier decontamination of resistant spores. PMID:19581364

  20. Procoagulant activity in patients with sickle cell trait.

    PubMed

    Lawrie, Andrew S; Pizzey, Arnold; Trompeter, Sara; Meiselman, Herbert; Mohandas, Narla; Dumanski, Jan P; Westerman, Maxwell P

    2012-06-01

    Patients with sickle cell trait (STr) are usually considered to be asymptomatic. However, complications, including hypercoagulability, increased risk of venous thromboembolism and the exertional exercise syndrome with rhabdomyolysis and sudden death, have been described. The exact cause of these adverse events is unclear. We have investigated two patients, a set of monozygotic twins with STr, to establish their procoagulant activity status as a potential indicator of thrombotic risk. In-vivo thrombin generation was assessed by the measurement of prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT). D-dimer was used as a marker of fibrinolytic activity. The potential to generate thrombin was determined using an ex-vivo thrombin generation test (TGT). The impact of red blood cell (RBC)-derived microparticle shedding and RBC rheology were examined. TAT (>60 μg/l) and F1 + 2 (948 pmol/l) were markedly elevated in patient 2 but within the normal reference range in patient 1 (TAT = 2.5 μg/l; F1 + 2 = 138 pmol/l). D-dimer levels (0.9 mg/l FEU) were similarly elevated in both patients. TGT peak thrombin and endogenous thrombin potential (ETP) were elevated to similar degrees in both patients. Flow cytometric analysis for RBC-derived microparticles showed that both patients had elevated levels on two occasions. RBC deformability, blood viscosity and RBC aggregation were normal and similar in both patients. The results demonstrated different coagulation activity in the patients with one patient in a prothrombotic state, suggesting that there may be two levels of hypercoagulability in STr. Measurement of such differences would allow for separation of high and low-risk patients from serious complications. PMID:22343687

  1. Development of the Patient Activation Measure for mental health.

    PubMed

    Green, Carla A; Perrin, Nancy A; Polen, Michael R; Leo, Michael C; Hibbard, Judith H; Tusler, Martin

    2010-07-01

    Our objective was to adapt the physical health Patient Activation Measure (PAM) for use among people with mental health conditions (PAM-MH). Data came from three studies among people with chronic mental health conditions and were combined in Rasch analyses. The PAM-MH's psychometric properties equal those of the original 13-item PAM. Test-retest reliability and concurrent validity were good, and the PAM-MH showed sensitivity to change. The PAM-MH appears to be a reliable and valid measure of patient activation among individuals with mental health problems. It appears to have potential for use in assessing change in activation. PMID:19728074

  2. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    PubMed Central

    Draborg, Anette Holck; Sandhu, Noreen; Larsen, Nanna; Lisander Larsen, Janni; Jacobsen, Søren; Houen, Gunnar

    2016-01-01

    We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1β, IFNγ, TNFα, TNFβ, TGFβ, and GM-CSF) were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFβ, IL1β, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients. PMID:27110576

  3. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients.

    PubMed

    Draborg, Anette Holck; Sandhu, Noreen; Larsen, Nanna; Lisander Larsen, Janni; Jacobsen, Søren; Houen, Gunnar

    2016-01-01

    We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1β, IFNγ, TNFα, TNFβ, TGFβ, and GM-CSF) were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFβ, IL1β, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients. PMID:27110576

  4. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

    PubMed Central

    Chader, Driss; Cohen-Aubart, Fleur; Haroche, Julien; Fadlallah, Jehane; Claër, Laetitia; Musset, Lucile; Gorochov, Guy; Amoura, Zahir; Miyara, Makoto

    2015-01-01

    Background/Purpose A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE. Methods We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score. Results Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2. Conclusion IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE. PMID:26629828

  5. Progress in defining clinically meaningful changes for clinical trials in nonrenal manifestations of SLE disease activity.

    PubMed

    Choi, Chan-Bum; Liang, Matthew H; Bae, Sang-Cheol

    2016-01-01

    Since the 2002 Dusseldorf meeting, one new agent, Benlysta, has been approved by the US Food and Drug Administration for systemic lupus erythematosus. Experiences from the field in conducting trials of all the agents tested during this period have provided valuable practical insights. There has been incremental progress in defining the minimal clinically important difference (MCID) of key disease manifestations and the view is largely that of the health care providers and not that of the person suffering the disease. This basic methodological work on the MCID should improve the efficiency and the clinical relevance of future trials and their design. PMID:26732314

  6. [Physical activity in patients with microvascular complications of diabetes].

    PubMed

    Matoulek, Martin

    2015-04-01

    Physical activity is often underestimated and little used in the treatment of diabetes. The fear of damage, especially in patients with diabetes complications is one of the reasons why it occurs. Physical activity plays an important role in prevention of the progression of peripheral neuropathy and its impact is primarily on the development of muscle strength and the ability to replace the function of nerve fibers damaged disabilities. Demonstrable effect on neuropathy is already recorded a few weeks of regular exercise, long-term programs then demonstrate the safety of occurrence of ulcers in compliance with basic foot care. Present autonomic neuropathy cannot predict response to cardiac respectively, heart rate and blood pressure. Due to other risks (silent ischemia, arrhythmia etc.), it is appropriate to stress test before a prescription of exercise programs. Monitoring of blood pressure, heart rate and blood glucose during the first hours of physical activity is necessary. In patients with autonomic neuropathy of the gastrointestinal tract may significantly affect the composition of the diet not only the ability of physical activity, but can also affect hypoglycaemia due to a slow carbohydrate absorption in these patients. Another risk in patients with autonomic neuropathy is orthostatic hypotension, which may potentiate antihypertensive drugs in "white coat" hypertension. Prescription of patients with retinopathy depends on the form and degree of retinopathy. Only proliferative retinopathy can significantly reduce exercise prescription, and it is always necessary to consult with ophthalmologist. In patients with nephropathy is an important stage of renal insufficiency for prescription of physical activity. Prescription is then influenced by the degree of renal insufficiency in addition to the presence of other associated diseases (anemia, hypertension, osteopathy etc.). Physical activity is essential in patients on dialysis respectively. After renal

  7. The Influence of Health Literacy and Patient Activation on Patient Information Seeking and Sharing.

    PubMed

    Ledford, Christy J W; Cafferty, Lauren A; Russell, Travis C

    2015-01-01

    This study provided an assessment of how patients looked for information to prepare for a clinical appointment and whether they shared those findings with their provider. A cross-sectional survey allowed insight into patient attitudes, motivations, and behavior in clinical real time. At two hospital-based clinics, 243 patients completed surveys before and after clinical appointments. Younger patients with higher communicative and critical health literacy prepared for clinical appointments with information searches. The predicted association of health literacy and patient activation with information sharing was not supported. This study shows that patients with higher patient activation perceived that their providers responded more positively to patient-obtained medical information. The role of critical health literacy may show that individuals choosing to seek information are considering not just their ability to conduct the search but also their ability to synthesize and critically analyze the results of the information search. An implication for providers is to become skilled in directly asking or passively surveying what outside information sources the patient has engaged with, no matter if the patient does or does not introduce the information. PMID:26513034

  8. Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schonlein purpura and systemic lupus erythematosus

    SciTech Connect

    Beale, M.G.; Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.

    1982-01-01

    The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schonlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determied in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 x/divide 1.33 ng/ml) followed by IgG (1754 x/divide 1.32 ng/ml) and IgM (404 x/divide 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 x/divide 1.20 and 4438 x/divide 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 x/divide 1.66 ng/ml. PWM stimulation of pateient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulted co-cultures, patient T cells nonspecifically suppressed the synthetic activities of autologous and control B cells. in contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement.

  9. Severity of dry eye syndrome is related to anti-dsDNA autoantibody in systemic lupus erythematosus patients without secondary Sjogren syndrome: A cross-sectional analysis.

    PubMed

    Chen, Alexander; Chen, Hung-Ta; Hwang, Yih-Hsiou; Chen, Yi-Tsun; Hsiao, Ching-Hsi; Chen, Hung-Chi

    2016-07-01

    There are as many as one-third of the systemic lupus erythematosus (SLE) patients who suffer from dry eye syndrome. To this date, dry eye syndrome in SLE patients is believed to be caused by secondary Sjogren syndrome (sSS). However, there is increasing evidence for possible independency of dry eye syndrome and sSS in patients suffering from autoimmune diseases. The purpose of this retrospective observational case series was to identify SLE patients without sSS who had dry eye syndrome, examine the correlation of different autoantibodies and dry eye severity, and determine the cause of dry eye in these patients.We included 49 consecutive SLE patients with dry eye who visited our dry eye clinic. In order to rule out sSS, these patients were all negative for anti-Sjogren's-syndrome-related antigen A and B (anti-SSA/SSB) and had no oral symptoms. Each patient's lupus activity was determined by serological tests including antidouble-stranded DNA antibody (anti-dsDNA), complement levels (C3, C4), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA). Severity of dry eye syndrome was determined by corneal sensation (KSen), superficial punctuate keratopathy (SPK), Schirmer-I test (Schirmer), and tear film break-up time (TBUT). The autoantibodies and the dry eye parameters in each group were tested using the χ test or the Mann-Whitney U test for normally distributed or skewed data, respectively.The anti-dsDNA showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.042) but not TBUT. The C3 showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.014) but not TBUT. No correlations of dry eye parameters were observed between C4, ESR, and ANA.The major finding of this study was that the severity of dry eye syndrome in SLE patients without sSS was strongly correlated with anti-dsDNA and C3 but not with C4, ESR, and ANA. PMID:27428227

  10. Severity of dry eye syndrome is related to anti-dsDNA autoantibody in systemic lupus erythematosus patients without secondary Sjogren syndrome

    PubMed Central

    Chen, Alexander; Chen, Hung-Ta; Hwang, Yih-Hsiou; Chen, Yi-Tsun; Hsiao, Ching-Hsi; Chen, Hung-Chi

    2016-01-01

    Abstract There are as many as one-third of the systemic lupus erythematosus (SLE) patients who suffer from dry eye syndrome. To this date, dry eye syndrome in SLE patients is believed to be caused by secondary Sjogren syndrome (sSS). However, there is increasing evidence for possible independency of dry eye syndrome and sSS in patients suffering from autoimmune diseases. The purpose of this retrospective observational case series was to identify SLE patients without sSS who had dry eye syndrome, examine the correlation of different autoantibodies and dry eye severity, and determine the cause of dry eye in these patients. We included 49 consecutive SLE patients with dry eye who visited our dry eye clinic. In order to rule out sSS, these patients were all negative for anti-Sjogren's-syndrome-related antigen A and B (anti-SSA/SSB) and had no oral symptoms. Each patient's lupus activity was determined by serological tests including antidouble-stranded DNA antibody (anti-dsDNA), complement levels (C3, C4), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA). Severity of dry eye syndrome was determined by corneal sensation (KSen), superficial punctuate keratopathy (SPK), Schirmer-I test (Schirmer), and tear film break-up time (TBUT). The autoantibodies and the dry eye parameters in each group were tested using the χ2 test or the Mann–Whitney U test for normally distributed or skewed data, respectively. The anti-dsDNA showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.042) but not TBUT. The C3 showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.014) but not TBUT. No correlations of dry eye parameters were observed between C4, ESR, and ANA. The major finding of this study was that the severity of dry eye syndrome in SLE patients without sSS was strongly correlated with anti-dsDNA and C3 but not with C4, ESR, and ANA. PMID:27428227

  11. Cast adrift: Gortex cast liners allow greater patient activity.

    PubMed

    Dubowitz, Gerald; Miller, Deborah M

    2003-01-01

    Extremity fractures are a common injury, with nearly 1.5 million cases reported in the United States in 1998. Treatment often involves lengthy periods of immobilization. This report outlines the use of a Gortex cast liner by a subject who was able to engage in swimming and scuba diving during the healing process. We report that a Gortex cast liner may be considered for an active patient who is keen to return to limited activities during fracture healing. Apparently because of a lack of knowledge of their existence, physicians currently are underutilizing this method of casting in active patients. The use of Gortex liners elsewhere has been reported to have higher patient and physician satisfaction in both use and performance, with no reported detrimental effects on outcome. PMID:14518627

  12. Demoralization, Patient Activation, and the Outcome of Spine Surgery.

    PubMed

    Block, Andrew R

    2016-01-01

    It is now well established that psychosocial factors can adversely impact the outcome of spine surgery. This article discusses in detail one such recently-identified "risk" factor: demoralization. Several studies conducted by the author indicate that demoralization, an emotional construct distinct from depression, is associated with poorer pain reduction, less functional improvement and decreased satisfaction among spine surgery patients. However, there are indications that the adverse impact of risk factors such as demoralization can be mitigated by psychosocial "maximizing" factors-characteristics that propel the patient towards positive surgical results. One of these maximizing factors, patient activation, is discussed in depth. The patient activation measure (PAM), an inventory assessing the extent to which patients are active and engaged in their health care, is associated not only with improved spine surgery results, but with better outcomes across a broad range of medical conditions. Other maximizing factors are discussed in this article. The author concludes that the past research focus on psychosocial risk factors has limited the value of presurgical psychological screening, and that future research, as well as clinical assessment, should recognize that the importance of evaluating patients' strengths as well as their vulnerabilities. PMID:27417599

  13. Infliximab treatment reduces complement activation in patients with rheumatoid arthritis

    PubMed Central

    Familian, A; Voskuyl, A; van Mierlo, G J; Heijst, H; Twisk, J; Dijkmans, B; Hack, C

    2005-01-01

    Background: Tumour necrosis factor (TNF) blocking agents decrease C reactive protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may contribute to complement activation in RA. Objective: To assess the effect of intravenous infliximab treatment on complement activation, especially that mediated by CRP, in RA. Methods: 35 patients with active RA (28 joint count Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma levels of complement activation products, of CRP and of CRP-complement complexes, which are specific markers for CRP mediated complement activation, were assessed at the indicated time points up to 22 weeks. The relationship between CRP and CRP-complement complexes was analysed by paired t test between two time points and by generalised estimated equation, to test differences of variables over time. Results: At 2 weeks after the first dose, infliximab significantly reduced overall C3 and C4 activation and plasma levels of CRP and CRP-complement complexes were also significantly reduced at this time point. The effects of infliximab on CRP and complement continued throughout the observation period and were more pronounced in patients with a good response to infliximab treatment. Conclusion: Treatment with infliximab decreases plasma levels of CRP and CRP dependent complement activation products and concomitantly may reduce complement activation in RA. Complement activation may be among the effector mechanisms of TNF in RA. PMID:15958758

  14. 25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Tay, Sen Hee; Ho, Chung Shun; Ho, Roger Chun-Man; Mak, Anselm

    2015-01-01

    Objectives Cognitive dysfunction has been reported in 20–80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction. Methods Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D3 and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry. Results In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D3 levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D3 deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D3 (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs. Conclusions Deficiency of 25(OH)D3, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients. PMID:26636681

  15. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  16. Desialylation of dying cells with catalytically active antibodies possessing sialidase activity facilitate their clearance by human macrophages

    PubMed Central

    Tomin, A; Dumych, T; Tolstyak, Y; Kril, I; Mahorivska, I; Bila, E; Stoika, R; Herrmann, M; Kit, Y; Bilyy, R

    2015-01-01

    Recently we reported the first known incidence of antibodies possessing catalytic sialidase activity (sialidase abzymes) in the serum of patients with multiple myeloma and systemic lupus erythematosus (SLE). These antibodies desialylate biomolecules, such as glycoproteins, gangliosides and red blood cells. Desialylation of dying cells was demonstrated to facilitate apoptotic cell clearance. In this study we assessed the possibility to facilitate dying cell clearance with the use of F(ab)2 fragments of sialidase abzymes. Two sources of sialidase abzymes were used: (i) those isolated from sera of patients with SLE after preliminary screening of a cohort of patients for sialidase activity; and (ii) by creating an induced sialidase abzyme through immunization of a rabbit with synthetic hapten consisting of a non-hydrolysable analogue of sialidase reaction conjugated with bovine serum albumin (BSA) or keyhole limpet haemocyanin (KLH). Antibodies were purified by ammonium sulphate precipitation, protein-G affinity chromatography and size exclusion-high performance liquid chromatography (HPLC-SEC). Effect of desialylation on efferocytosis was studied using human polymorphonuclear leucocytes (PMN), both viable and aged, as prey, and human monocyte-derived macrophages (MoMa). Treatment of apoptotic and viable prey with both disease-associated (purified from blood serum of SLE patients) and immunization-induced (obtained by immunization of rabbits) sialidase abzymes, its F(ab)2 fragment and bacterial neuraminidase (as positive control) have significantly enhanced the clearance of prey by macrophages. We conclude that sialidase abzyme can serve as a protective agent in autoimmune patients and that artificial abzymes may be of potential therapeutic value. PMID:24580640

  17. Distribution of Active and Resting Periods in the Motor Activity of Patients with Depression and Schizophrenia

    PubMed Central

    Hauge, Erik; Berle, Jan Øystein; Dilsaver, Steven; Oedegaard, Ketil J.

    2016-01-01

    Objective Alterations of activity are prominent features of the major functional psychiatric disorders. Motor activity patterns are characterized by bursts of activity separated by periods with inactivity. The purpose of the present study has been to analyze such active and inactive periods in patients with depression and schizophrenia. Methods Actigraph registrations for 12 days from 24 patients with schizophrenia, 23 with depression and 29 healthy controls. Results Patients with schizophrenia and depression have distinctly different profiles with regard to the characterization and distribution of active and inactive periods. The mean duration of active periods is lowest in the depressed patients, and the duration of inactive periods is highest in the patients with schizophrenia. For active periods the cumulative probability distribution, using lengths from 1 to 35 min, follows a straight line on a log-log plot, suggestive of a power law function, and a similar relationship is found for inactive periods, using lengths from 1 to 20 min. For both active and inactive periods the scaling exponent is higher in the depressed compared to the schizophrenic patients. Conclusion The present findings add to previously published results, with other mathematical methods, suggesting there are important differences in control systems regulating motor behavior in these two major groups of psychiatric disorders. PMID:26766953

  18. Serum paraoxonase 1 activity in patients with iron deficiency anemia

    PubMed Central

    Gedikbasi, Asuman; Akalin, Nilgul; Gunaldi, Meral; Yilmaz, Deniz; Mert, Meral; Harmankaya, Ozlem; Soylu, Aliye; Karakaya, Pinar; Kumbasar, Abdulbaki

    2016-01-01

    Introduction In this study we aimed to detect paraoxonase 1 (PON-1) activity in iron deficiency anemia (IDA) and to compare it with healthy controls by observing the change after iron therapy. Material and methods In this study, 50 adult patients with IDA and 40 healthy subjects were enrolled. All patients were analyzed at the beginning and after treatment according to laboratory assessments. Results Mean paraoxonase and arylesterase activities in the iron deficiency anemia group were significantly lower than mean activities of the control group (102.4 ±19.2 U/l and 163.3 ±13.68 U/l, respectively and 157.3 ±26.4 U/l and 256.1 ±24.6 U/l, respectively; p = 0.0001 for both). Paraoxonase and arylesterase activities significantly increased after treatment for IDA (143.2 ±13.9 and 197.6 ±27.9 U/l, respectively, p = 0.0001). Mean activities after treatment with iron were significantly lower than mean activities in the control group (p = 0.002; p = 0.0001 respectively). Conclusions Paraoxonase and arylesterase activities in patients with IDA significantly increased after treatment with iron therapy. In adults IDA may also be one of the factors associated with increased risk of atherosclerosis. PMID:27478448

  19. Complement Activation in Trauma Patients Alters Platelet Function.

    PubMed

    Atefi, Gelareh; Aisiku, Omozuanvbo; Shapiro, Nathan; Hauser, Carl; Dalle Lucca, Jurandir; Flaumenhaft, Robert; Tsokos, George C

    2016-09-01

    Trauma remains the main cause of death for both civilians and those in uniform. Trauma-associated coagulopathy is a complex process involving inflammation, coagulation, and platelet dysfunction. It is unknown whether activation of complement, which occurs invariably in trauma patients, is involved in the expression of trauma-associated coagulopathy. We designed a prospective study in which we enrolled 40 trauma patients and 30 healthy donors upon arrival to the emergency department of BIDMC. Platelets from healthy individuals were incubated with sera from trauma patients and their responsiveness to a thrombin receptor-activating peptide was measured using aggregometry. Complement deposition on platelets from trauma patients was measured by flow cytometry. Normal platelets displayed hypoactivity after incubation with trauma sera even though exposure to trauma sera resulted in increased agonist-induced calcium flux. Depletion of complement from sera further blocked activation of hypoactive platelets. Conversely, complement activation increased aggregation of platelets. Platelets from trauma patients were found to have significantly higher amounts of C3a and C4d on their surface compared with platelets from controls. Depletion of complement (C4d, C3a) reversed the ability of trauma sera to augment agonist-induced calcium flux in donor platelets. Our data indicate that complement enhances platelet aggregation. Despite its complement content, trauma sera render platelets hypoactive and complement depletion further blocks activation of hypoactive platelets. The defect in platelet activation induced by trauma sera is distal to receptor activation since agonist-induced Ca2+ flux is elevated in the presence of trauma sera owing to complement deposition. PMID:27355402

  20. Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE

    PubMed Central

    Domingues, Vinicius; Magder, Laurence S; Petri, Michelle

    2016-01-01

    Objective The Sydney classification criteria for antiphospholipid syndrome include lupus anticoagulant or moderate-to-high titre anticardiolipin IgG or IgM. We explored the association of all anticardiolipin isotypes, lupus anticoagulant and the combination with venous and arterial thrombosis. Methods Patients with systemic lupus erythematosus (SLE) in a large clinical cohort seen quarterly were repeatedly tested by protocol for anticardiolipin antibodies and lupus anticoagulant. Subgroups of patients were defined based on the geometric mean titres of IgG, IgM, IgA anticardiolipin and lupus anticoagulant expressed in dilute Russell's viper venom time (RVVT) seconds for each patient across all cohort visits. These subgroups were compared with respect rates of thrombosis since diagnosis with SLE. Rate ratios were estimated using Cox Proportional Hazards models. Results Of the 1390 cohort members included, there were 284 thrombotic events observed over 17 025 person-years since diagnosis for a rate of 1.7 events per 100 person-years. Those with a geometric mean titre of IgG anticardiolipin >20 had a significantly elevated rate of thromboses (rate ratio 1.8, p=0.0052), whereas there was no evidence of an association between thromboses and elevated IgM geometric mean (rate ratio 1.2, p=0.40). There were relatively few cohort members with elevated IgA geometric mean but the rate of thromboses in that group was elevated (rate ratio 1.7, p=0.23). The associations between anticardiolipin antibodies and thromboses were strongest when considering venous thromboses. Those with two or more elevated anticardiolipin isotypes or those with both IgG anticardiolipin and RVVT did not appear at higher risk than those with a single elevated marker. Conclusion This study supports previous observations that IgG anticardiolipin and lupus anticoagulant are associated with higher rates of thromboses. Our power to study IgA anticardiolipin was limited due to small number of patients with

  1. Does modafinil enhance activity of patients with myotonic dystrophy?

    PubMed Central

    Lammers, G.J.; van Dijk, J.G.

    2007-01-01

    We performed a double-blind placebo-controlled crossover study in 13 patients with myotonic dystrophy to address the question whether modafinil, known to improve hypersomnolence in myotonic dystrophy, may improve levels of activity as well. We used the Epworth Sleepiness Scale as a measure of hypersomnolence and a structured interview of the patient and the partner or housemate as a measure of activity. We additionally used a restricted form of the RAND-36 to relate a possible improvement of activity to perceived general health. We confirmed earlier positive findings of modafinil regarding reduced somnolence (p = 0.015), but no significant effects were seen regarding activity levels (p = 0.2 for patients’ self-reports and 0.5 for partners’ reports). PMID:17285226

  2. Prevalence of LDL atherogenic phenotype in patients with systemic lupus erythematosus

    PubMed Central

    Olusi, Samuel O; George, Sunila

    2011-01-01

    Background: Patients with systemic lupus erythematosus (SLE) are 5–8 times more likely to develop coronary heart disease than the general population. The aim of this study was to find out the prevalence of the small dense low-density lipoprotein (LDL) cholesterol particle in patients with SLE. Methods: We recruited 50 consecutive patients with SLE who had no evidence of hypertension or renal failure. Fifty age- and gender-matched healthy controls were also recruited. We measured serum lipid levels and LDL particle diameters by gradient gel electrophoresis in both patients and controls. Results: Patients with SLE had significant dyslipidemia, characterized by elevated plasma triglycerides, LDL cholesterol, Apoprotein B, triglyceride:high-density (HDL) lipoprotein cholesterol ratio, and decreased plasma concentrations of HDL cholesterol. The LDL particle size in SLE (24.8 ± 1.23 nm) was significantly (P < 0.01) smaller than that in controls (26.1 ± 1.31 nm). The prevalence of the LDL phenotype B (the atherogenic phenotype) was 52% in SLE but only 20% in healthy controls. Conclusion: We conclude that the high prevalence of small dense LDL in SLE may contribute to the high incidence of coronary heart disease seen in this disorder. PMID:21415920

  3. Non Activated Protein C Supplementation in Septic Pediatric Hematological Patients

    PubMed Central

    Perillo, Teresa; Muggeo, Paola; Arcamone, Giampaolo; Leonardis, Francesco De; Santoro, Nicola

    2016-01-01

    The purpose of the study was to examine safety and efficacy of non-activated Protein C (PC) supplementation in our cohort of septic pediatric hematological patients. We conducted a retrospective study of 22 septic patients receiving human plasma-derived PC concentrate from 2008 to 2015 at our Pediatric Oncology Center (Bari, Italy). The Surviving sepsis campaign definitions for sepsis, severe sepsis and septic shock were used to define the patients’ septic status. For each patient, we calculated Lansky performance status scale (LPSS) and a risk score defined the Hematologic risk score (HRS) that we created in 2007. Patients were defined as High risk for severe sepsis/septic shock in case of HRS>3. HRS<3 identified low risk patients. Baseline serum PC levels, PC administration dosage and duration and days until a 20% improvement in LPSS. Observed baseline serum PC levels (bPC) blood concentrations ranged from 31 to 80%. Patients received PC supplementation in case of low age-related bPC levels or >10% PC concentration decrease within 12 hours from the first evaluation. All patients received 80 U/kg/day PC, intravenously, every twenty-four hours. No drug-related adverse event was observed. The observed sepsis-related mortality rate in our cohort was 9%. PC supplementation in our cohort appeared to be safe, and, probably due to prompt PC administration, we observed an overall mortality that was much lower than expected mortality in cancer severe septic patients. PMID:27433305

  4. Demoralization, Patient Activation, and the Outcome of Spine Surgery

    PubMed Central

    Block, Andrew R

    2016-01-01

    It is now well established that psychosocial factors can adversely impact the outcome of spine surgery. This article discusses in detail one such recently-identified “risk” factor: demoralization. Several studies conducted by the author indicate that demoralization, an emotional construct distinct from depression, is associated with poorer pain reduction, less functional improvement and decreased satisfaction among spine surgery patients. However, there are indications that the adverse impact of risk factors such as demoralization can be mitigated by psychosocial “maximizing” factors—characteristics that propel the patient towards positive surgical results. One of these maximizing factors, patient activation, is discussed in depth. The patient activation measure (PAM), an inventory assessing the extent to which patients are active and engaged in their health care, is associated not only with improved spine surgery results, but with better outcomes across a broad range of medical conditions. Other maximizing factors are discussed in this article. The author concludes that the past research focus on psychosocial risk factors has limited the value of presurgical psychological screening, and that future research, as well as clinical assessment, should recognize that the importance of evaluating patients’ strengths as well as their vulnerabilities. PMID:27417599

  5. Motolimod effectively drives immune activation in advanced cancer patients

    PubMed Central

    Dietsch, Gregory N.

    2016-01-01

    ABSTRACT A novel approach to immunotherapy is the activation of toll-like receptor 8 (TLR8). Motolimod, a selective TLR8 agonist can act in concert with approved immunotherapies to sensitize T cells and augment natural killer (NK) cell function. Despite treatment with chemotherapeutic agents and advance disease, cancer patients remain sensitive to motolimod.

  6. Exercise in Treating Hypertension: Tailoring Therapies for Active Patients.

    ERIC Educational Resources Information Center

    Chintanadilok, Jirayos

    2002-01-01

    Exercise can be definitive therapy for some, and adjunctive therapy for many, people with hypertension, though people with secondary hypertension may not derive as much benefit. Low-to- moderate-intensity aerobic exercise can help with mild hypertension and reduce drug dosages in more severe cases. For active patients requiring medication,…

  7. Chest pain in lupus patients: the emergency department experience.

    PubMed

    Modi, Masoom; Ishimori, Mariko L; Sandhu, Vaneet K; Wallace, Daniel J; Weisman, Michael H

    2015-11-01

    Heart disease, a major cause of morbidity and mortality in SLE patients, often manifests as chest pain (CP). Our goal was to understand the prevalence and outcome of CP presentations for SLE patients in the emergency department (ED). Billing records of patients who presented to Cedars-Sinai Medical Center ED with ICD-9 codes for SLE and secondary ICD-9 codes for CP (786.50-786.59) between March 2009 and October 2013 were reviewed. Two study groups were formed: discharge from ED versus hospital admission. Visits were evaluated for basic cardiac work-up with an electrocardiogram (EKG) and cardiac enzymes; hospital admissions were evaluated for CP etiology and discharge diagnoses. Of 2675 ED visits with ICD-9 codes for SLE, 397 visits had secondary codes for CP (15%); 173 were discharged and 224 became hospital admissions. While 92% of admissions had basic cardiac work-up, over 50% had chest pain attributed to non-cardiac causes. Only 7.2% had a discharge diagnosis related to cardiovascular disease. Fifteen percent of all SLE coded patients had complaints of CP, a figure higher than the national average for non-SLE CP (10%). There is a majority of non-cardiac diagnoses given to SLE patients at discharge. CP is likely to be a window of opportunity to address the known cardiac morbidity and mortality in SLE patients perhaps at an early stage of development of this complication. Our study strengthens the need for more investigations to assess the etiology of CP in this population. PMID:25912215

  8. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    SciTech Connect

    Cai Ping; Koenig, Rolf; Boor, Paul J.; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Khan, M. Firoze; Ansari, G.A.S.

    2008-04-01

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice.

  9. IgG immunoadsorption reduces systemic lupus erythematosus activity and proteinuria: a long term observational study

    PubMed Central

    Stummvoll, G; Aringer, M; Smolen, J; Schmaldienst, S; Jimenez-Boj, E; Horl, W; Graninger, W; Derfler, K

    2005-01-01

    Objective: To analyse the effects of rigorous immunoglobulin removal by immunoadsorption (IAS) on proteinuria (primary outcome variable), disease activity (SIS, SLEDAI, ECLAM), and autoantibodies to double stranded DNA (anti-dsDNA) in active systemic lupus erythematosus (SLE). Methods: 16 patients with severe SLE and renal disease, in whom cyclophosphamide was contraindicated or failed to halt disease progression, were treated with IAS for 3 months. Patients achieving at least 20% improvement in two or more of the outcome measures were considered responders and offered a 9 months' extension period. Results: Within 3 months, 14 patients responded and 11 opted for an extension. Proteinuria decreased from 6.7 (4.6) g/day (mean (SD)) at baseline to 4.3 (3.5) g/day at 3 months and 2.9 (2.4) g/day at 12 months (p<0.001). From baseline to 3 and 12 months, disease activity improved independently of scoring by SIS (15 (5) to 5 (2) and to 5 (2), p<0.0001), SLEDAI (21 (7) to 5 (4) and to 5 (4), p<0.0001), or ECLAM (7 (2) to 2 (1) and to 3 (1), p<0.0001). Anti-dsDNA fell from 391 (647) IU/ml to 146 (218) and to 53 (50) IU/ml at 3 and 12 months, respectively. Steroids could be tapered from 117 (159) mg/day at baseline to 29 (17) mg/day at 3 months and 9 (2) mg/day at 12 months. IAS was not associated with an excess of infections. However, one patient died of septicaemia after 1 month of treatment. Conclusion: In this negatively selected cohort of patients with SLE, IAS was associated with a significant response shown by reduced proteinuria, improved global disease activity, decreased anti-dsDNA, and lower glucocorticoid dosages, suggesting therapeutic benefit. PMID:15640267

  10. Patient activation and advocacy: which literacy skills matter most?

    PubMed

    Martin, Laurie T; Schonlau, Matthias; Haas, Ann; Derose, Kathryn Pitkin; Rosenfeld, Lindsay; Buka, Stephen L; Rudd, Rima

    2011-01-01

    Attention to the effect of a patient's literacy skills on health care interactions is relatively new. So, too, are studies of either structural or personal factors that inhibit or support a patient's ability to navigate health services and systems and to advocate for their own needs within a service delivery system. Contributions of the structural environment, of interpersonal dynamics, and of a variety of psychological and sociological factors in the relationship between patients and providers have long been under study. Less frequently examined is the advocacy role expected of patients. However, the complex nature of health care in the United States increasingly requires a proactive stance. This study examined whether four literacy skills (reading, numeracy, speaking, and listening) were associated with patient self-advocacy--a component of health literacy itself--when faced with a hypothetical barrier to scheduling a medical appointment. Although all literacy skills were significantly associated with advocacy when examined in isolation, greater speaking and listening skills remained significantly associated with better patient advocacy when all four skills were examined simultaneously. These findings suggest that speaking and listening skills and support for such skills may be important factors to consider when developing patient activation and advocacy skills. PMID:21951251

  11. Effect of trimebutine on colonic myoelectrical activity in IBS patients.

    PubMed

    Frexinos, J; Fioramonti, J; Bueno, L

    1985-01-01

    The effect of trimebutine 100 mg i.v. and placebo on colonic myoelectrical activity was investigated in 10 patients with the irritable bowel syndrome (IBS) (5 constipated and 5 diarrhoeic), using an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited two kinds of spike bursts: short spike bursts (SSB) localized at one electrode site and appearing rhythmically at 10.3/min, and long spike bursts (LSB), isolated or propagated orally or aborally. Computerized analysis of the duration of each kind of spike burst showed that, as compared to the control, trimebutine 100 mg, selectively inhibited by 43 to 73% the mean duration of LSB activity in the transverse, descending and sigmoid colon, from 0 to 30 min after administration. The inhibitory effect was similar in constipated and diarrhoeic patients. Placebo injection did not significantly affect (p greater than 0.05) the duration of LSB and SSB activity. Variance analysis indicated that the inhibitory effect of trimebutine was significantly greater (p less than 0.05) on LSB activity in the transverse than the descending colon, and that it was absent from the sigmoid colon. The results suggest that trimebutine selectively inhibits the propulsive activity of the proximal two thirds of the colon in IBS patients, and that this effect cannot entirely explain its therapeutic efficacy in IBS. PMID:3987797

  12. Brain activation induced by psychological stress in patients with schizophrenia.

    PubMed

    Castro, M N; Villarreal, M F; Bolotinsky, N; Papávero, E; Goldschmidt, M G; Costanzo, E Y; Drucaroff, L; Wainsztein, A; de Achával, D; Pahissa, J; Bär, K-J; Nemeroff, C B; Guinjoan, S M

    2015-10-01

    Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions. PMID:26190301

  13. Superantigen influence in conjunction with cytokine polymorphism potentiates autoimmunity in systemic lupus erythematosus patients.

    PubMed

    Dar, Sajad Ahmad; Janahi, Essam Mohammed Ahmed; Haque, Shafiul; Akhter, Naseem; Jawed, Arshad; Wahid, Mohd; Ramachandran, Vishnampettai Ganapathysubramanian; Bhattacharya, Sambit Nath; Banerjee, Basu Dev; Das, Shukla

    2016-08-01

    Risk posed by microbial superantigens in triggering or exacerbating SLE in genetically predisposed individuals, thereby altering the response to its treatment strategies, has not been studied. Using streptococcal pyrogenic exotoxin A and staphylococcal enterotoxin B as prototype superantigens, we have demonstrated that they profoundly affect the magnitude of polyclonal T cell response, particularly CD4(+) T cells and expression of CD45RA and CD45RO, and cytokine secretion in vitro in SLE patient PBMCs. Also, reduced proportions of FoxP3 expressing CD4(+)CD25(+) T cells were detected in SLE as compared to healthy control PBMCs. Furthermore, polymorphism in IL-10 and TGF-β showed significant association with SLE in our study population. These results indicate that accumulation of superantigen-reactive T cells and cytokine polymorphism may cause disease exacerbation, relapse, or therapeutic resistance in SLE patients. Attempts to contain colonizing and/or superantigen-producing microbial agents in SLE patients in addition to careful monitoring of their therapy may be worthwhile in decreasing disease severity or preventing frequent relapses. The study suggests that superantigen interference in conjunction with cytokine polymorphism may play a role in immune dysregulation, thereby contributing to autoimmunity in SLE. Therefore, changes in T cell phenotypes and cytokine secretion might be good indicators of therapeutic efficacy in these patients. PMID:26676360

  14. Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease

    PubMed Central

    Farias, Fabiana H. G.; Bremer, Hanna D.; Hedlund, Anna; Pielberg, Gerli R.; Seppälä, Eija H.; Gustafson, Ulla; Lohi, Hannes; Carlborg, Örjan; Andersson, Göran; Hansson-Hamlin, Helene; Lindblad-Toh, Kerstin

    2015-01-01

    The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients’ sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANAH) and speckled ANA (ANAS) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAMTOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans. PMID:26057447

  15. Rupture of renal artery aneurysm due to Salmonella infection in a patient with systemic lupus erythematosus.

    PubMed

    Chiu, K M; Lin, T Y; Chen, J S; Chu, S H

    2008-02-01

    Patients with systemic lupus erythematosus (SLE) are prone to infection. Immunomodulation treatment increases the susceptibility. Salmonella infections in SLE patients may present with various clinical pictures, like pneumonia, septic arthritis, osteomyelitis, peritonitis, abscess and so on. The vascular complications commonly seen in the general population with salmonella infection are rarely encountered in SLE patients. Here we report an SLE patient who presented with spontaneous rupture of salmonella mycotic aneurysm involving the left renal artery. The 54 year-old woman had a stable premorbid condition and had 30 mg prednisolone per day. Acute abdomen and hypotensive shock developed suddenly without warning signs in advance. Image and tissue culture confirmed the diagnosis. The patient had an uneventful recovery. The rare clinical scenario is reported. PMID:18250138

  16. Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy.

    PubMed

    Sollet, Jean-Pierre; Garber, Gary E

    2002-12-01

    Selecting patients for drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) therapy outside of a clinical trial setting requires knowledge of the rationale that led the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) investigators to select the various entry criteria for the trial. Enrollment criteria for the study included a known or suspected infection, presence of at least 3 systemic inflammatory response syndrome (SIRS) criteria, and dysfunction of > or =1 organ or system. The infection criteria used in PROWESS were designed to be straightforward and were based on common clinical and radiological data. Although previous definitions of sepsis required only 2 SIRS criteria, the PROWESS trial investigators required the presence of > or =3 SIRS criteria to improve the sensitivity and specificity of these criteria for the diagnosis of sepsis. Acute organ dysfunction, the diagnostic criterion for severe sepsis, was used to define the study population because it identifies patients at significant risk of death. Characteristics of drotrecogin alfa (activated)-treated patients, including infection, modified SIRS criteria, and organ dysfunction, were similar to those of the placebo group and the general sepsis population. Proper clinical judgment and use of the these inclusion criteria as a guide will help clinicians select and treat sepsis patients with drotrecogin alfa (activated). PMID:12521613

  17. Barriers associated with reduced physical activity in COPD patients*

    PubMed Central

    Amorim, Priscila Batista; Stelmach, Rafael; Carvalho, Celso Ricardo Fernandes; Fernandes, Frederico Leon Arrabal; Carvalho-Pinto, Regina Maria; Cukier, Alberto

    2014-01-01

    OBJECTIVE: To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score. METHODS: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. RESULTS: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001). The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. CONCLUSIONS: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures. PMID:25410838

  18. Increased Risk of Systemic Lupus Erythematosus in 29,000 Patients with Biopsy-verified Celiac Disease

    PubMed Central

    LUDVIGSSON, JONAS F.; RUBIO-TAPIA, ALBERTO; CHOWDHARY, VAIDEHI; MURRAY, JOSEPH A.; SIMARD, JULIA F.

    2012-01-01

    Objective To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking. Methods We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden’s 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register. SLE was defined as having at least 2 records of SLE in the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR) for SLE. Results During followup, 54 individuals with CD had an incident SLE. This corresponded to an HR of 3.49 (95% CI 2.48–4.90), with an absolute risk of 17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of followup, the HR for SLE was 2.54 (95% CI 1.57–4.10). While SLE was predominantly female, we found similar risk estimates in men and women. When we restricted our outcome to individuals who also had a dispensation for a medication used in SLE, the HR was 2.43 (95% CI 1.22–4.87). The HR for having 2 records of SLE diagnoses, out of which at least 1 had occurred in a department of rheumatology, nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97–4.17). Conclusion Individuals with CD were at a 3-fold increased risk of SLE compared to the general population. Although this excess risk remained more than 5 years after CD diagnosis, absolute risks were low. PMID:22859356

  19. Asymmetric pallidal neuronal activity in patients with cervical dystonia.

    PubMed

    Moll, Christian K E; Galindo-Leon, Edgar; Sharott, Andrew; Gulberti, Alessandro; Buhmann, Carsten; Koeppen, Johannes A; Biermann, Maxine; Bäumer, Tobias; Zittel, Simone; Westphal, Manfred; Gerloff, Christian; Hamel, Wolfgang; Münchau, Alexander; Engel, Andreas K

    2014-01-01

    The origin of asymmetric clinical manifestation of symptoms in patients suffering from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal activity in the basal ganglia has been suggested to have a role in the pathophysiology of CD. Here, we re-assessed the question to what extent relative changes occur in the direct vs. indirect basal ganglia pathway in CD, whether these circuit changes are lateralized, and how these alterations relate to CD symptoms. To this end, we recorded ongoing single cell and local field potential (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13 CD patients undergoing microelectrode-guided stereotactic surgery for deep brain stimulation in the GPi. We compared pallidal recordings from CD patients operated under local anaesthesia (LA) with those obtained in CD patients operated under general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of head turning was higher than contralateral and correlated with torticollis symptom severity. Lateralized differences were absent at the level of the GPe and in recordings from patients operated under GA. Furthermore, in the GPi of CD patients there was a subpopulation of theta-oscillatory cells with unique bursting characteristics. Power and coherence of GPe- and GPi-LFPs were dominated by a theta peak and also exhibited band-specific interhemispheric differences. Strong cross-frequency coupling of low-gamma amplitude to theta phase was a feature of pallidal LFPs recorded under LA, but not GA. These results indicate that CD is associated with an asymmetric pallidal outflow. Based on the finding of symmetric neuronal discharges in the GPe, we propose that an imbalanced interhemispheric direct pathway gain may be involved in CD pathophysiology. PMID:24574981

  20. Overweight Is a Major Contributor to Atherosclerosis in Systemic Lupus Erythematosus Patients at Apparent Low Risk for Cardiovascular Disease

    PubMed Central

    Sacre, Karim; Escoubet, Brigitte; Zennaro, Maria-Christina; Chauveheid, Marie-Paule; Gayat, Etienne; Papo, Thomas

    2015-01-01

    Abstract Cardiovascular disease (CVD) is the main cause of death in systemic lupus erythematosus (SLE) patients. We aimed to determine whether overweight (defined as a body mass index [BMI] > 25 kg/m2) contributed to subclinical atherosclerosis in SLE patients at low risk for CVD according to traditional factors. Wall thickness of the internal carotid artery (ICWT) measured at the carotid bulb and carotid plaques were assessed in 49 SLE patients asymptomatic for CVD and 49 controls matched on Framingham score. Factors associated to ICWT were identified and multivariate analysis was performed. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (mean 1.9 ± 3.5 in SLE vs 1.8 ± 3.2% in controls, P = 0.37). ICWT (P < 0.001) and number of patients with carotid plaques (P = 0.015) were, however, higher in SLE patients as compared to controls. In multivariable analysis, SLE was an independent risk for a carotid atherosclerosis (OR [95% confidence interval, CI]: 3.53 [1.36–9.14]; P = 0.009). Older age, higher BMI, and higher Framingham score were associated with atherosclerosis in SLE patients in univariate analysis. In multivariate analysis, only the association with overweight remained significant (OR [95% CI]: 4.13 [1.02–16.75]; P = 0.047). Overweight is a major contributor to atherosclerosis in SLE patients at apparent low risk for CVD. PMID:26632902

  1. Basophil Activation Test with Food Additives in Chronic Urticaria Patients

    PubMed Central

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU. PMID:24527415

  2. Step activity monitoring in lumbar stenosis patients undergoing decompressive surgery

    PubMed Central

    Schubert, Tim; Winter, Corinna; Brandes, Mirko; Hackenberg, Lars; Wassmann, Hansdetlef; Liem, Dennis; Rosenbaum, Dieter; Bullmann, Viola

    2010-01-01

    Symptomatic degenerative central lumbar spinal stenosis (LSS) is a frequent indication for decompressive spinal surgery, to reduce spinal claudication. No data are as yet available on the effect of surgery on the level of activity measured with objective long-term monitoring. The aim of this prospective, controlled study was to objectively quantify the level of activity in central LSS patients before and after surgery, using a continuous measurement device. The objective data were correlated with subjective clinical results and the radiographic degree of stenosis. Forty-seven patients with central LSS and typical spinal claudication scheduled for surgery were included. The level of activity (number of gait cycles) was quantified for 7 consecutive days using the StepWatch Activity Monitor (SAM). Visual analogue scales (VAS) for back and leg pain, Oswestry disability index and Roland–Morris score were used to assess the patients’ clinical status. The patients were investigated before surgery and 3 and 12 months after surgery. In addition, the radiographic extent of central LSS was measured digitally on preoperative magnetic resonance imaging or computed tomography. The following results were found preoperatively: 3,578 gait cycles/day, VAS for back pain 5.7 and for leg pain 6.5. Three months after surgery, the patients showed improvement: 4,145 gait cycles/day, VAS for back pain 4.0 and for leg pain 3.0. Twelve months after surgery, the improvement continued: 4,335 gait cycles/day, VAS for back pain 4.1 and for leg pain 3.3. The clinical results and SAM results showed significant improvement when preoperative data were compared with data 3 and 12 months after surgery. The results 12 months after surgery did not differ significantly from those 3 months after surgery. The level of activity correlated significantly with the degree of leg pain. The mean cross-sectional area of the spinal canal at the central LSS was 94 mm2. The radiographic results did not

  3. Garre's sclerosing osteomyelitis caused by salmonella group D in a patient with systemic lupus erythematosus: an unusual complication.

    PubMed

    Elera-Fitzcarrald, Claudia; Alfaro-Lozano, José L; Pastor-Asurza, César A

    2015-12-01

    We report the case of a 35-year-old male, who was diagnosed with systemic lupus erythematosus (SLE) in 2010 based on the presence of articular, serous, renal, immune, and hematologic involvement. He also had secondary antiphospholipid syndrome (APS). He was treated with prednisone 10 mg per day, hydroxychloroquine 200 mg per day, methotrexate 12.5 mg per week, leflunomide 20 mg per day, and oral anticoagulation previous to the present event. He presented to emergency room with a 7 day disease duration characterized by pain in the left thigh, which increased with physical activity, resulting in claudication; he also had malaise and fever. The X-ray films showed periostitis of the lower half of the left femur with bone marrow narrowing; the scintigraphy showed marked increased uptake in the middle and distal thirds of the left femur, and magnetic resonance imaging (MRI) showed thickening and hyperintensity of the cortex of the diaphysis and distal epiphysis of the femur and endosteal irregularity. Empirical treatment was started with vancomycin for 3 weeks. Femur biopsy and cultures were performed, isolating Salmonella spp. group "D" Vi (-); treatment with cotrimoxazole and ceftazidime for 4 weeks followed by doxycycline and cotrimoxazole for 4 months were given with a favorable functional outcome. This is an unusual case of a young adult with Garre's sclerosing osteomyelitis associated to SLE and caused by salmonella. The literature is reviewed and the clinical conditions predisposing to this infection are discussed, particularly in patients with SLE. PMID:26511966

  4. Patient Participation and Physical Activity during Rehabilitation and Future Functional Outcomes in Patients following Hip Fracture

    PubMed Central

    Lenze, Eric J.; Munin, Michael C.; Harrison, Christopher C; Brach, Jennifer S

    2016-01-01

    Objective We examined the association between physical activity recorded by Actigraphy during therapy sessions (therapy) to therapist rated patient participation and self reported future functional outcomes. We hypothesized those participants who were more active during rehab would have higher participation scores and better functional outcomes following hip fracture compared to those who were less active. Design Longitudinal study with 3 and 6 month follow-up. Setting Participants were recruited from skilled nursing (SN) and inpatient rehabilitation (IR) facilities. Participants Participants included 18 community dwelling older adults admitted to SN or IR facilities after hip fracture. Participants were included if they were ≥ 60 years of age and ambulatory with or without assistance from a device or another person. Intervention Not Applicable Main Outcome Measure Physical activity was quantified during participants’ rehab using the Actigraph accelerometer worn consecutively over 5 days. The Pittsburgh Participation Rating Scale was used to quantify patient participation during their inpatient therapy sessions. Self reported functional outcomes were measured by the Hip Fracture Functional Recovery Scale (HFRS) at baseline, 3 and 6 months following fracture. Results Participants with higher Actigraphy counts during rehab were ranked by their therapists as having excellent participation compared to those who were less active. Participants who were more active reported better functional abilities at both 3 and 6 month time points and achieved 78% and 91% recovery of self reported pre-fracture function compared to those who were less active achieving 64% and 73% recovery. Conclusion Actigraphy provides an objective measure of physical activity exhibiting predictive validity for future functional outcomes and concurrent validity against patient participation in patients after hip fracture. PMID:19345777

  5. Interferon-induced 2'-5' adenylate synthetase in vivo and interferon production in vitro by lymphocytes from systemic lupus erythematosus patients with and without circulating interferon

    SciTech Connect

    Preble, O.T.; Rothko, K.; Klippel, J.H.; Friedman, R.M.; Johnston, M.I.

    1983-06-01

    The interferon (IFN)-induced enzyme 2-5A synthetase was elevated in mononuclear cells from both serum IFN-positive and -negative systemic lupus erythematosus (SLE) patients. This suggests that a much higher percentage of patients than previously thought produce endogenous IFN. These results may partly explain findings that mononuclear cells from SLE patients are deficient in IFN production in vitro in response to certain IFN inducers. Although normal lymphocytes can produce an acid-labile alpha IFN after stimulation with C. parvum in vitro, the reason for endogenous production of this unusual alpha IFN by SLE patients remains unknown.

  6. Sexual Activity and Heart Patients: A Contemporary Perspective.

    PubMed

    Stein, Ricardo; Sardinha, Aline; Araújo, Claudio Gil S

    2016-04-01

    Sexual activity (SA) encompasses several behaviors such as kissing (Ki), touching (T), oral (O) stimulation, masturbation (M), and vaginal/anal intercourse (I). The acronym KiTOMI is proposed here to represent these behaviors. SA, particularly coitus, is a major aspect of health-related quality of life and is often considered the most pleasant and rewarding exercise performed during an entire lifetime. Although several studies have been conducted on sexuality, relatively limited information is available regarding SA in patients with heart disease. Moreover, the level of evidence of this limited information is nearly always B or C. This article provides a comprehensive and updated review of the relevant literature and offers evidence and expert-based practical messages regarding SA in patients with heart disease. Considering the rationale for exercise prescription, SA is typically well tolerated by most clinically stable patients with heart disease. Even in more debilitated and sicker individuals, KiT activities would most likely be feasible and desirable. The absolute risk of major adverse cardiovascular events during SA is typically very low. Even lower death rates have been reported for specific groups, such as women in general, aerobically fit men, and asymptomatic young adults with congenital heart disease. Finally, we emphasize the relevance of sexual counselling for patients and their partners, including the proper use of medications to treat erectile dysfunction. Counselled patients will be reassured and adequately informed regarding how to gradually resume habitual SA after a major cardiac event or procedure, starting with KiT and progressively advancing to KiTOM until all KiTOMI activities are allowed. PMID:26690295

  7. The Effect of a Patient Portal With Electronic Messaging on Patient Activation Among Chronically Ill Patients: Controlled Before-and-After Study

    PubMed Central

    Linna, Miika; Rönkkö, Ilona

    2014-01-01

    Background It has been suggested that providing patients with access to their medical records and secure messaging with health care professionals improves health outcomes in chronic care by encouraging and activating patients to manage their own condition. Objectives The aim was to evaluate the effect of access to a patient portal on patient activation among chronically ill patients. Further, the relationship between temporal proximity of a severe diagnosis and patient activation were assessed. Methods A total of 876 chronically ill patients from public primary care were allocated to either an intervention group receiving immediate access to a patient portal that included their medical records, care plan, and secure messaging with a care team, or to a control group receiving usual care. Patient Activation Measure (PAM) at baseline and at 6-month follow-up was obtained from 80 patients in the intervention group and 57 patients in the control group; thus, a total of 137 patients were included in the final analysis. Results No significant effect of access to patient portal on patient activation was detected in this study (F 1,133=1.87, P=.17, η2=0.01). Patients starting at a lower level of activation demonstrated greater positive change in activation compared to patients starting at higher levels of activation in both the intervention and control groups. Further, patients diagnosed with a severe diagnosis during the intervention showed greater positive change in patient activation compared to patients whose last severe diagnosis was made more than 2 years ago. The results also suggest that the intervention had greatest effect on patients starting at the highest level of patient activation (difference in change of patient activation=4.82, P=.13), and among patients diagnosed within a year of the intervention (difference in change of patient activation=7.65, P=.12). Conclusions Time since last severe diagnosis and patient activation at baseline may affect changes in

  8. Evaluation of macrophage antiviral activity in patients affected by neoplasia.

    PubMed

    Merendino, R A; Iannello, D; Arena, A; Bonina, L; Greco, V; Mesiti, M; Chillemi, S; Mastroeni, P

    1988-01-01

    The intrinsic antiviral activity of macrophages has been studied in healthy donors and in patients affected by breast cancer and melanoma. In vitro differentiated macrophages from blood-derived monocytes were infected with measles virus, herpes simplex virus type 2 and adenovirus 17. The challenge was carried out with different multiplicities of infection and the synthesis of virus was tested by evaluating the single cycle growth curve in 24 h. The results obtained show that the restriction of virus infectivity by macrophages is strongly influenced by the multiplicity of infection. This was particularly evident with the adenovirus 17. Moreover, macrophages from patients with melanoma and breast cancer showed an impairment of the intrinsic antiviral activity in comparison with normal subjects. PMID:2842553

  9. Paraoxonase Activity and Oxidative Status in Patients with Tinnitus

    PubMed Central

    Akyüz, Servet; Somuk, Battal Tahsin; Soyalic, Harun; Yılmaz, Beyhan; Taskin, Abdullah; Bilinc, Hasan; Aksoy, Nurten

    2016-01-01

    Background and Objectives The aim of this study was to investigate serum paraoxanase-1 (PON) activity, total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) in tinnitus; and to compare the results with data from healthy subjects. Subjects and Methods A total of 114 subjects-54 patients with tinnitus and 60 healthy controls were enrolled in this study. Serum PON activity, TOS, TAS, and OSI levels were measured. Results In the tinnitus group, TAS, and PON were significantly lower than in the control group (p<0.001). However, the TOS, and OSI levels were significantly higher in the tinnitus group than in the control group (p<0.001). Conclusions According to the data obtained from the present study, patients with tinnitus were exposed to potent oxidative stress. Oxidative stress may be the key contributing factor to the pathogenesis of tinnitus. PMID:27144229

  10. Factors affecting daily activities of patients with cerebral infarction

    PubMed Central

    Liu, Peng; Zhou, Cheng-ye; Zhang, Ying; Wang, Yun-feng; Zou, Chang-lin

    2010-01-01

    BACKGROUND: Stroke is the leading cause of death and long-term disability. This study was undertaken to investigate the factors influencing daily activities of patients with cerebral infarction so as to take interventional measures earlier to improve their daily activities. METHODS: A total of 149 patients with first-episode cerebral infarction were recruited into this prospective study. They were admitted to the Encephalopathy Center, Department of Neurology, the First Affiliated Hospital of Wenzhou Medical College in Zhejiang Province from August 2008 to December 2008. The baseline characteristics of the patients and cerebral infarction risk factors on the first day of admission were recorded. White blood cell (WBC) count, plasma glucose (PG), and many others of laboratory targets were collected in the next morning. Barthel index (BI) was calculated at 2 weeks and 3 months respectively after onset of the disease at the outpatient clinic or by telephone call. Lung infection, urinary tract infection and atrial fibrillation if any were recorded on admission. The National Institute of Health Stroke Scale (NIHSS) scores and the GCS scores were recorded within 24 hours on and after admission, at the second week, and at the third month after the onset of cerebral infarction respectively. RESULTS: The factors of BI at 2 weeks and 3 months after onset were the initial PG level, WBC count and initial NIHSS scores. Besides, urinary tract infection on admission was also the factor for BI at 3 months. CONCLUSION: Active measures should be taken to control these factors to improve the daily activities of patients with cerebral infarction. PMID:25214953

  11. The prevalence of antiphospholipid antibody syndrome among systemic lupus erythematosus patients.

    PubMed

    McMahon, M A; Keogan, M; O'Connell, P; Kearns, G

    2006-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by excess autoantibody production. It typically affects women of childbearing age. Antiphospholipid antibody syndrome (APLAs) is associated with serious co-morbidity to mother and child characterized by recurrent vascular thrombosis and/or pregnancy associated morbidity. We reviewed SLE patients attending a specialist connective tissue disease clinic both to assess the occurrence of APLAs and its clinical presentations and to audit the effectiveness of screening for APL antibodies in a specialist clinic. 204 patients attended the newly established connective tissue disease outpatient clinic over a twenty-seven month period; 42 (34 female, 8 male) with a diagnosis of SLE. Ten patients (24%), eight female and 2 male with a median age of 38.5 years (range 20 to 64 years) fulfilled the ACR criteria for secondary APLAs (Table 2). The commonest clinical presentation was pulmonary embolus (five patients). Overall 37 patients (88%) with SLE were screened for APLAs during the study period: 94% of females and 62.5% of males were screened (for anticardiolipin antibodies, lupus anticoagulant or both), 27% had evidence of APLAs, 24% had positive antibodies but were asymptomatic. There is a significant occurrence of APLAs among SLE patients. Given the important clinical implications of this disorder including substantial risk of fetal loss and patient morbidity or mortality, routine screening of all SLE patients for APL antibodies is recommended. PMID:17274170

  12. Genetic variants and disease-associated factors contribute to enhanced IRF-5 expression in blood cells of systemic lupus erythematosus patients

    PubMed Central

    Feng, Di; Stone, Rivka C.; Program, MD/PhD; Eloranta, Maija-Leena; Sangster-Guity, Niquiche; Nordmark, Gunnel; Sigurdsson, Snaevar; Wang, Chuan; Alm, Gunnar; Syvänen, Ann-Christine; Rönnblom, Lars; Barnes, Betsy J.

    2010-01-01

    Objective Genetic variants of the interferon (IFN) regulatory factor 5 (IRF5) gene are associated with systemic lupus erythematosus (SLE) susceptibility. The contribution of these variants to IRF-5 expression in primary blood cells of SLE patients has not been addressed, nor has the role of type I IFN. The aim of this study was to determine the association between increased IRF-5 expression and the IRF5 risk haplotype in SLE patients. Methods IRF-5 transcript and protein levels in 44 Swedish patients with SLE and 16 healthy controls were measured by quantitative real-time PCR, minigene assay, and flow cytometry. The rs2004640, rs10954213, rs10488631 and the CGGGG indel were genotyped in these patients. Genotypes of these polymorphisms defined a common risk and protective haplotype. Results IRF-5 expression and alternative splicing were significantly upregulated in SLE patients versus healthy donors. Enhanced transcript and protein levels were associated with the risk haplotype of IRF5; rs10488631 gave the only significant independent association that correlated with increased transcription from non-coding exon 1C. Minigene experiments demonstrated an important role for rs2004640 and the CGGGG indel, along with type I IFNs in regulating IRF-5 expression. Conclusions This study provides the first formal proof that IRF-5 expression and alternative splicing are significantly upregulated in primary blood cells of SLE patients. The risk haplotype is associated with enhanced IRF-5 transcript and protein expression in SLE patients. PMID:20112383

  13. The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus

    PubMed Central

    Rasaei, Nakisa; Shams, Mesbah; Kamali-Sarvestani, Eskandar; Nazarinia, Mohammad Ali

    2015-01-01

    Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. Objectives: The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies. Patients and Methods: This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody. Results: The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups. Conclusions: Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients. PMID:26756002

  14. A comparative proteomic study of sera in paediatric systemic lupus erythematosus patients and in healthy controls using MALDI-TOF-TOF and LC MS–A pilot study

    PubMed Central

    2012-01-01

    Background Paediatric systemic lupus erythematosus (pSLE) exhibits an aggressive clinical phenotype with severe complications and overall poor prognosis. The aim of this study was to analyse differential expression of low molecular weight (LMW) serum protein molecules of pSLE patients with active disease in comparison to sera of healthy age matched controls. Further, some of the differential expressed spots were characterised and identified by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) and liquid chromatography (LC-MS). Methods 2D-PAGE was performed using pooled sera of active pSLE and age matched healthy controls. Gels were silver-stained and differentially expressed protein spots were detected by automated image master platinum 2D software. 79 ± 17 protein spots were detected for control gels and 78 ± 17 protein spots for patient gels. Of these eleven protein spots were selected randomly and characterized by MALDI-TOF MS (five protein spots) and LC MS (six protein spots) techniques. Results Out of the 11 protein spots, 5 protein spots were significantly upregulated viz., leiomodin 2 (LMOD2); epidermal cytokeratin 2; immunoglobulin kappa light chain variable region; keratin 1 and transthyretin (TTR). Three protein spots were significantly down regulated e.g., apolipoprotein A1 (APOA1); chain B human complement component C3c; campath antibody antigen complex. Two protein spots (complement component C3; retinol binding protein (RBP) were found to be expressed only in disease and one protein spot cyclohydrolase 2 was only expressed in controls. Conclusions We conclude that 2-D maps of patients with active pSLE and controls differ significantly. In this pilot study, using proteomic approach we have identified differential expressed proteins (of LMW) e.g., RBP, LMOD 2, TTR, Component C3c Chain B and APO A1. However, in future, further studies need to confirm the physiological and pathological role of these

  15. Health Literacy and Education as Mediators of Racial Disparities in Patient Activation Within an Elderly Patient Cohort.

    PubMed

    Eneanya, Nwamaka D; Winter, Michael; Cabral, Howard; Waite, Katherine; Henault, Lori; Bickmore, Timothy; Hanchate, Amresh; Wolf, Michael; Paasche-Orlow, Michael K

    2016-01-01

    The Patient Activation Measure (PAM) assesses facets of patient engagement to identify proactive health behaviors and is an important predictor of health outcomes. Health literacy and education are also important for patient participation and successful navigation of the health care system. Because health literacy, education, and patient activation are associated with racial disparities, we sought to investigate whether health literacy and education would mediate racial differences in patient activation. Participants were 265 older adults who participated in a computer-based exercise interventional study. Health literacy was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Of 210 eligible participants, 72% self-identified as Black and 28% as White. In adjusted analyses, education and health literacy each significantly reduced racial differences in patient activation. These findings are especially important when considering emerging data on the significance of patient activation and new strategies to increase patient engagement. PMID:27524777

  16. Geometric complexity identifies platelet activation in familial hypercholesterolemic patients.

    PubMed

    Bianciardi, Giorgio; Aglianò, Margherita; Volpi, Nila; Stefanutti, Claudia

    2015-06-01

    Familial hypercholesterolemia (FH), a genetic disease, is associated with a severe incidence of athero-thrombotic events, related, also, to platelet hyperreactivity. A plethora of methods have been proposed to identify those activated circulating platelets, none of these has proved really effective. We need efficient methods to identify the circulating platelet status in order to follow the patients after therapeutic procedures. We propose the use of computerized fractal analysis for an objective characterization of the complexity of circulating platelet shapes observed by means of transmission electron microscopy in order to characterize the in vivo hyperactivated platelets of familial hypercholesterolemic patients, distinguishing them from the in vivo resting platelets of healthy individuals. Platelet boundaries were extracted by means of automatically image analysis. Geometric complexity (fractal dimension, D) by box counting was automatically calculated. The platelet boundary observed by electron microscopy is fractal, the shape of the circulating platelets is more complex in FH (n = 6) than healthy subjects (n = 5, P < 0.01), with 100% correct classification in selected individuals. In vitro activated platelets from healthy subjects show an analogous increase of D. The observed high D in the platelet boundary in FH originates from the in vivo platelet activation. Computerized fractal analysis of platelet shape observed by transmission electron microscopy can provide accurate, quantitative data to study platelet activation in familial hypercholesterolemia and after administration of drugs or other therapeutic procedures. PMID:25877374

  17. Resting state activity in patients with disorders of consciousness.

    PubMed

    Soddu, Andrea; Vanhaudenhuyse, Audrey; Demertzi, Athena; Bruno, Marie-Aurélie; Tshibanda, Luaba; Di, Haibo; Mélanie, Boly; Papa, Michele; Laureys, Steven; Noirhomme, Quentin

    2011-01-01

    Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients' active collaboration in data acquisition. PMID:21693087

  18. Evidence for brain glial activation in chronic pain patients.

    PubMed

    Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

    2015-03-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. PMID:25582579

  19. Low prevalence of Blastocystis sp. in active ulcerative colitis patients.

    PubMed

    Rossen, N G; Bart, A; Verhaar, N; van Nood, E; Kootte, R; de Groot, P F; D'Haens, G R; Ponsioen, C Y; van Gool, T

    2015-05-01

    Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5-49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0-37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls. PMID:25680316

  20. Evidence for altered opioid activity in patients with cancer.

    PubMed Central

    Lissoni, P.; Barni, S.; Paolorossi, F.; Crispino, S.; Rovelli, F.; Ferri, L.; Delitala, G.; Tancini, G.

    1987-01-01

    Endogenous opioid peptides have been shown to be involved in the regulation of tumour growth. At present, however, no data are available about the secretion of opioid peptides in cancer patients. To draw some preliminary conclusions on opioid brain function in human neoplasms, we evaluated hypophyseal hormone responses to the administration of a met-enkephalin analogue, FK 33-824. The study included 14 patients affected by early or advanced neoplastic disease, 12 healthy subjects and 7 patients with a chronic medical illness other than cancer. FK 33-824 was given intravenously at a dose of 0.3 mg. Venous blood samples were collected at zero time, and 30, 60 and 120 min after drug administration. In each sample, PRL, GH, LH, cortisol and beta-endorphin levels were measured by RIA. In all normal subjects and in patients with non-neoplastic chronic illness, FK 33-824 induced a rise in PRL and GH levels, and a decrease in LH, cortisol and beta-endorphin. A normal endocrine response to FK 33-824 was seen in our cancer patient only, while in the other cases with tumour no hormonal changes or a paradoxical response were seen after FK 33-824. Based on the fact that an abnormal endocrine response to FK 33-824 has been described in hypothalamic-pituitary disorders, in which anomalous brain opioid activity has been demonstrated, these results suggest the existence of an altered function of the opioid system in cancer patients, the clinical importance of which remains to be determined. PMID:2963662

  1. Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis

    PubMed Central

    Stremmel, W; Merle, U; Zahn, A; Autschbach, F; Hinz, U; Ehehalt, R

    2005-01-01

    Background and aims: We examined the hypothesis of an anti-inflammatory effect of phosphatidylcholine in ulcerative colitis. Methods: A phase IIA, double blind, randomised, placebo controlled study was performed in 60 patients with chronic active, non steroid dependent, ulcerative colitis, with a clinical activity index (CAI) of ⩾4. Retarded release phosphatidylcholine rich phospholipids and placebo were administered at a dose of 6 g daily over three months. The primary end point was a change in CAI towards clinical remission (CAI ⩽3) or CAI improvement by ⩾50%. Secondary end points included ⩾50% changes in endoscopic activity index (EAI), histology, and quality of life scores. Results: Induction of clinical remission (CAI ⩽3) as the primary outcome variable was attained by 16 (53%) patients in the phosphatidylcholine treated group compared with three (10%) in the placebo group (p<0.00001). The rate of clinical remission and CAI improvement was 90% in the phosphatidylcholine group and only 10% in the placebo group. A median drop of seven points in the CAI score (70% improvement) was recorded in the phosphatidylcholine group compared with no change in the placebo group. Secondary end point analysis revealed concomitant drops in EAI and histology scores (p = 0.00016 and p = 0.0067 compared with placebo, respectively). Improvement in quality of life was reported by 16 of 29 evaluated patients in the phosphatidylcholine group compared with two of 30 in the placebo group (p = 0.00005). Conclusion: Retarded release oral phosphatidylcholine is effective in alleviating inflammatory activity caused by ulcerative colitis. PMID:15951544

  2. Why and how should we measure disease activity and damage in lupus?

    PubMed

    Feld, Joy; Isenberg, David

    2014-06-01

    The assessment of disease activity and flare and differentiating them from permanent damage in patients with SLE is challenging. The SLEDAI, SLEDAI-2K and SELENA-SLEDAI measure global disease activity. The BILAG measures organ-specific activity. The BILAG better captures the change in the different organs at the expense of complexity. The SRI is a composite index incorporating both BILAG and SLEDAI indices and a physician's global assessment. It has been used in the most recent clinical trials. Damage correlates with prognosis; it is assessed by the SLICC/SDI index. This index scores damage whatever the cause, disease or treatment related, or the consequence of concomitant disease. The disease activity and damage indices do not correlate well with the patient's health related quality of life (HRQoL), the degree of disability or the impact of disease. The impact of the patients' joint disease on their HRQoL is assessed via the HAQ questionnaire and the global health status via the SF-36 index, or one of the more recently described lupus specific quality of life indices [Lupus QoL]. The global assessment instruments and the BILAG index can also be used in children and adolescents with SLE. However, a modified paediatric version of the SLICC/SDI damage index is advised. Many advances have been achieved in disease activity and damage measurement in the past 20 years but the problem of how best to capture flare accurately remains. PMID:24791651

  3. Evidence for brain glial activation in chronic pain patients

    PubMed Central

    Loggia, Marco L.; Chonde, Daniel B.; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R.; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D.; Zürcher, Nicole R.; Albrecht, Daniel S.; Vangel, Mark G.; Rosen, Bruce R.; Napadow, Vitaly; Hooker, Jacob M.

    2015-01-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand 11C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for 11C-PBR28, nine patient–control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29–63 for patients and 28–65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. PMID:25582579

  4. Dynamic hyperinflation during activities of daily living in COPD patients.

    PubMed

    Silva, Cláudia S; Nogueira, Fabiana R; Porto, Elias F; Gazzotti, Mariana R; Nascimento, Oliver A; Camelier, Aquiles; Jardim, José R

    2015-08-01

    The objective of this study was to investigate whether some activities of daily living (ADLs) usually related to dyspnea sensation in patients with chronic obstructive pulmonary disease (COPD) are associated with dynamic lung hyperinflation (DH) and whether the use of simple energy conservation techniques (ECTs) might reduce this possible hyperinflation. Eighteen patients (mean age: 65.8 ± 9.8 years) with moderate-to-severe COPD performed six ADLs (walking on a treadmill, storing pots, walking 56 meters carrying a 5-kilogram weight, climbing stairs, simulating taking a shower, and putting on shoes) and had their inspiratory capacity (IC) measured before and after each task. The patients were moderately obstructed with forced expiratory volume in 1 second (FEV1): 1.4 ± 0.4 L (50% ± 12.4); FEV1/forced vital capacity: 0.4 ± 8.1; residual volume/total lung capacity: 52.7 ± 10.2, and a reduction in IC was seen after all six activities (p < 0.05): (1) going upstairs, 170 mL; (2) walking 56 meters carrying 5 kilogram weight, 150 mL; (3) walking on a treadmill without and with ECT, respectively, 230 mL and 235 mL; (4) storing pots without and with ECT, respectively, 170 mL and 128 mL; (5) taking a shower without and with ECT, respectively, 172 mL and 118 mL; and (6) putting on shoes without and with ECT, respectively, 210 mL and 78 mL). Patients with moderate to severe COPD develop DH after performing common ADLs involving the upper and lower limbs. Simple ECTs may avoid DH in some of these ADLs. PMID:25896955

  5. Active core rewarming avoids bioelectrical impedance changes in postanesthetic patients

    PubMed Central

    2011-01-01

    Background Postoperative hypothermia is a common cause of complications in patients who underwent laparoscopic cholecystectomy. Hypothermia is known to elicit electrophysiological, biochemical, and cellular alterations thus leading to changes in the active and passive membrane properties. These changes might influence the bioelectrical impedance (BI). Our aim was to determine whether the BI depends on the core temperature. Methods We studied 60 patients (52 female and 8 male) age 40 to 80 years with an ASA I-II classification that had undergone laparoscopic cholecystectomy under balanced inhalation anesthesia. The experimental group (n = 30) received active core rewarming during the transanesthetic and postanesthesic periods. The control group (n = 30) received passive external rewarming. The BI was recorded by using a 4-contact electrode system to collect dual sets of measurements in the deltoid muscle. The body temperature, hemodynamic variables, respiratory rate, blood-gas levels, biochemical parameters, and shivering were also measured. The Mann-Whitney unpaired t-test was used to determine the differences in shivering between each group at each measurement period. Measurements of body temperature, hemodynamics variables, respiratory rate, and BI were analyzed using the two-way repeated-measures ANOVA. Results The gradual decrease in the body temperature was followed by the BI increase over time. The highest BI values (95 ± 11 Ω) appeared when the lowest values of the temperature (35.5 ± 0.5°C) were reached. The active core rewarming kept the body temperature within the physiological range (over 36.5°C). This effect was accompanied by low stable values (68 ± 3 Ω) of BI. A significant decrease over time in the hemodynamic values, respiratory rate, and shivering was seen in the active core-rewarming group when compared with the controls. The temporal course of shivering was different from those of body temperatue and BI. The control patients showed a

  6. Colonic perforation in a patient with systemic lupus erythematosus accompanied by cytomegalovirus infection: A case report

    PubMed Central

    Tachikawa, Yuichi; Nozawa, Hiroaki; Tanaka, Junichiro; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Kazama, Shinsuke; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Fujisawa, Madoka; Takahashi, Katutoshi; Sakaguchi, Yoshiki; Ushiku, Tetsuo; Fukayama, Masashi; Watanabe, Toshiaki

    2016-01-01

    Introduction Cytomegalovirus (CMV) infection of the gastrointestinal tract is an uncommon illness, but can be observed in immunocompromised patients. Systemic lupus erythematosus (SLE) patients are generally at high risk of CMV infection. Here we report a subacute progressive case of colitis in SLE accompanied by cytomegalovirus infection. Presentation of case The patient, a 79-year-old woman, was hospitalized complaining of fever, polyarthritis, and skin ulcer that had lasted seven days. She additionally manifested vomiting, high fever, and right abdominal pain within two weeks thereafter, and was diagnosed with perforation of the intestine. Emergency operation was carried out for panperitonitis due to perforation of one of the multiple colon ulcers. Multidisciplinary postoperative treatment could not save her life. Pathological examination suggested that cytomegalovirus infection as well as cholesterin embolization contributed to the rapid progression of colitis. Discussion There have been only a limited number of case reports of CMV enteritis in SLE. Moreover, only two SLE patients on multiple medications have been reported to experience gastrointestinal perforation. Viral infections, including CMV, can induce clinical manifestations resembling SLE and for this reason we suspect that there are potentially many more patients misdiagnosed and/or unreported. Conclusion Our case underscores the importance of exploring the possibility of CMV infection as a differential diagnosis in SLE patients with obvious gastrointestinal symptoms who were treated by immunosuppressive drugs. PMID:27093690

  7. How do patients and doctors-to-be perceive systemic lupus erythematosus?

    PubMed

    Nowicka-Sauer, Katarzyna; Pietrzykowska, Małgorzata; Banaszkiewicz, Dorota; Hajduk, Adam; Czuszyńska, Zenobia; Smoleńska, Żaneta

    2016-05-01

    The aim of the present study was to assess and compare illness perception of systemic lupus erythematosus (SLE) held by 6th-year medical students and patients suffering from SLE. The study group consisted of 104 students (66 women; 63.5 %), mean age 24.7 (±1), and 64 outpatients with SLE (60 women; 93.7 %). All patients were treated at a university rheumatology outpatient clinic. Mean patients' age was 44.3 years (±12.5). Mean duration of the disease was 11 years (±6.8). The Polish version of Brief Illness Perception Questionnaire (B-IPQ) was used to assess five dimensions of illness perception. The students were asked to complete a modified version of B-IPQ designed to measure health professionals' illness perception. Significant differences were found in all but one B-IPQ scores. The students obtained significantly higher scores than the SLE patients in consequences, identity, concern and emotional response, whereas significantly lower scores in personal control, treatment control and understanding were noted among students. No differences were found in timeline scores. Medical students' perception of SLE is more threatening and more negative than that of patients'. Doctors-to-be perceive SLE as being less controllable, more burdensome and having more consequences than patients do. Additionally, they believe the disease causes more emotional concern. The article discusses possible explanations together with positive and negative aspects of the discrepancies. PMID:26873361

  8. Muscle activation patterns in patients with recurrent shoulder instability

    PubMed Central

    Jaggi, Anju; Noorani, Ali; Malone, Alex; Cowan, Joseph; Lambert, Simon; Bayley, Ian

    2012-01-01

    Purpose: The aim of this study is to present muscle patterns observed with the direction of instability in a series of patients presenting with recurrent shoulder instability. Materials and Methods: A retrospective review was carried out on shoulder instability cases referred for fine wire dynamic electromyography (DEMG) studies at a specialist upper limb centre between 1981 and 2003. An experienced consultant clinical neurophysiologist performed dual needle insertion into four muscles (pectoralis major (PM), latissimus dorsi (LD), anterior deltoid (AD) and infraspinatus (IS)) in shoulders that were suspected to have increased or suppressed activation of muscles that could be contributing to the instability. Raw EMG signals were obtained while subjects performed simple uniplanar movements of the shoulder. The presence or absence of muscle activation was noted and compared to clinical diagnosis and direction of instability. Results: A total of 140 (26.6%) shoulders were referred for fine wire EMG, and 131 studies were completed. Of the shoulders tested, 122 shoulders (93%) were identified as having abnormal patterns and nine had normal patterns. PM was found to be more active in 60% of shoulders presenting with anterior instability. LD was found to be more active in 81% of shoulders with anterior instability and 80% with posterior instability. AD was found to be more active in 22% of shoulders with anterior instability and 18% with posterior instability. IS was found to be inappropriately inactive in only 3% of shoulders with anterior instability but in 25% with posterior instability. Clinical assessment identified 93% of cases suspected to have muscle patterning, but the specificity of the clinical assessment was only correct in 11% of cases. Conclusion: The DEMG results suggest that increased activation of LD may play a role in both anterior and posterior shoulder instability; increased activation of PM may play a role in anterior instability. PMID:23493512

  9. Successful Hybrid Treatment for a Ruptured Thoracoabdominal Aortic Aneurysm in a Patient with Systemic Lupus Erythematosus

    PubMed Central

    2013-01-01

    A 49-year-old woman with a 27-year history of systemic lupus erythematosus (SLE) was admitted to our hospital with sudden-onset severe back pain. An emergency multidetector computed tomography (MDCT) revealed a ruptured thoracoabdominal aortic aneurysm (TAAA) 80 mm in diameter. Considering her condition and comorbidities, we performed an emergency hybrid treatment: visceral reconstruction followed by endoluminal aneurysm exclusion. She recovered uneventfully, except for the need for temporary hemodialysis. TAAA complicated with SLE is extremely rare. To our knowledge, this is the first successful report in the English literature of a ruptured TAAA in a patient with SLE who underwent hybrid treatment. PMID:23825503

  10. The emergence of systemic lupus erythematosus in hypothyroid patients: two case reports and mini review.

    PubMed

    Bakr, A; Laimon, W; El-Ziny, M A; Hammad, A; El-Hawary, A K; Elsharkawy, A A; El-Refaey, A M; Salem, N A; El-Mougy, A; Zedan, M M; Aboelenin, H M; Eid, R; Sarhan, A

    2014-07-01

    Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease that involves almost all the organs in the human body and is characterized by auto antibodies formation. Autoimmune thyroid diseases (AITD) are organ-specific diseases that are associated with a production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies, anti-cardiolipin antibodies, and others. The diagnosis of AITD in patients with SLE is well known, but the reverse is rarely reported. We present two cases of adolescent girls in whom SLE evolved one year after being diagnosed with hypothyroidism. PMID:24569395

  11. High tibial osteotomies in the young active patient

    PubMed Central

    Traub, Shaun; Efird, Chad

    2010-01-01

    Unicompartmental changes in the knee of a young athlete remains a difficult and controversial problem in orthopaedics. Excessive premature loading of articular cartilage, most often the result of a knee injury, has been shown to result in increased degenerative changes and pain in the younger patient. Instability may also contribute to the degeneration of cartilage and must therefore be considered in the treatment of osteoarthritis in the young adult. High tibial osteotomy has been described as a treatment option for malalignment in the older, less active adult and has shown promising results in a younger, more active population. Osteotomies for instability are more controversial and should be considered in more complex injury patterns. PMID:20076957

  12. 78 FR 53195 - Proposed Information Collection (Dental Patient Satisfaction Survey) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ... AFFAIRS Proposed Information Collection (Dental Patient Satisfaction Survey) Activity: Comment Request... patient satisfaction with VA's dental services. DATES: Written comments and recommendations on the... refer to ``OMB Control No. 2900-0764 (Dental Patient Satisfaction Survey)'' in any...

  13. Resting state activity in patients with disorders of consciousness

    PubMed Central

    Soddu, Andrea; Vanhaudenhuyse, Audrey; Demertzi, Athena; Bruno, Marie-Aurélie; Tshibanda, Luaba; Di, Haibo; Boly, Mélanie; Papa, Michele; Laureys, Steven; Noirhomme, Quentin

    Summary Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients’ active collaboration in data acquisition. PMID:21693087

  14. MHEALTH INTERVENTION DEVELOPMENT TO SUPPORT PATIENTS WITH ACTIVE TUBERCULOSIS

    PubMed Central

    Iribarren, Sarah J.; Beck, Susan L.; Pearce, Patricia F.; Chirico, Cristina; Etchevarria, Mirta; Rubinstein, Fernando

    2015-01-01

    Background Mobile Health (mHealth) based interventions have been increasingly used to improve a broad range of health outcomes. However, few researchers have reported on the process or the application of theory to guide the development of mHealth based interventions, or specifically for tuberculosis (TB) treatment management. Aims To describe the steps, process, and considerations in developing a text messaging-based intervention to promote treatment adherence and provide support to patients with active TB. Methods Traditional qualitative techniques, including semi-structured interviews, field notes, content analysis, iterative coding, and thematic analysis, were used to design and document the intervention development with a multidisciplinary team of researchers, clinicians, administrators, and patients who were in active TB treatment. The Information-Motivation-Behavioral Skills (IMB) model was used to guide the coding scheme for content analysis of patient-directed TB educational material and intervention development. Results The development steps included: a) establishing intervention components, including justifications, considerations, timing and frequency of components; b) developing educational messages, including cultural adaption, text or short message service (SMS) formatting, and prioritizing message delivery order; and c) determining implementation protocol. A set of 16 IMB-based messages were developed for the educational component. Final intervention development was achieved in 3 months. Conclusion A collaborative approach and application of a theory to guide the intervention design and development is supported. Although a collaborative approach was more time consuming, it resulted in a more responsive, culturally appropriate, and comprehensive intervention. Considerations for developing a text messaging based intervention are provided and may serve as a guide for similar interventions. Further empirical evidence is needed for applying the IMB model

  15. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities

    ERIC Educational Resources Information Center

    Chen, Jie; Mullins, C. Daniel; Novak, Priscilla; Thomas, Stephen B.

    2016-01-01

    Designing culturally sensitive personalized interventions is essential to sustain patients' involvement in their treatment and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and…

  16. Treatment of young patients with lupus nephritis using calcineurin inhibitors

    PubMed Central

    Tanaka, Hiroshi; Tsuruga, Kazushi; Aizawa-Yashiro, Tomomi; Watanabe, Shojiro; Imaizumi, Tadaatsu

    2012-01-01

    Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contributed to a favorable outcome in children and adolescents with systemic lupus erythematosus (SLE). Nevertheless, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are reviewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide (IVCY) are effective for preserving renal function in adult patients, CPA is a potent immunosuppressive agent that induces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malignancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting the transcription of the early activation genes of interleukin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone (PDN), Tac, and mycophenolate mofetile (MMF) has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and

  17. Antischistosomal activity of artemisinin derivatives in vivo and in patients.

    PubMed

    Saeed, Mohamed E M; Krishna, Sanjeev; Greten, Henry Johannes; Kremsner, Peter G; Efferth, Thomas

    2016-08-01

    Schistosomiasis is a helminthic disease affecting more than 200 million people in the tropics as well as returning travellers. Treatment mainly relies on a single drug, praziquantel. Praziquantel cannot kill developing schistosomula resulting in frequent treatment failures and re-infections. Monotherapy also favors the selection for resistance. New drugs are therefore urgently needed. The activity of the semi-synthetic artemisinin derivatives artemether, artesunate and arteether is not restricted to malaria. We reviewed their anti-schistosomal activity in vivo and in patients by searching the PubMed database for publications since 1983 with the search terms "artemisinin" and "Schistosoma". Reports on in vivo studies in animals and clinical trials in human beings were selected. S. mansoni, S. japonicum, and S. haematobium have been tested in mice, rabbits, hamsters, and dogs. These artemisinin derivatives strongly reduced total worm rates with stronger reduction rates for female worms than for males. The drugs also reduced egg burden and egg-caused granulomata in the host liver. Artemisinin-type drugs induced oxidative and metabolic stress leading to morphological damage and decreased fertility of the parasites. Although artemether and artesunate have been investigated in numerous clinical trials, the poor quality of many has led to inconsistent results and has not provided convincing evidence on the therapeutic value against schistosomiasis. Despite these methodological concerns, clinical trials may indicate anti-schistosomal activity in patients. Convincing clinical trials providing unambiguous evidence are now needed. Furthermore, suitable treatment protocols for combination therapy to prevent/treat praziquantel-resistant Schistosoma strains should be investigated. PMID:26902577

  18. Symptomatic knee osteonecrosis in patients with systemic lupus erythematosus: a case-control study.

    PubMed

    Zhao, Lidan; Wu, Xiuhua; Wu, Honghua; Su, Jinmei; Zhang, Wen; Zhao, Yan; Zhang, Xuan; Zheng, Wenjie

    2016-08-01

    To explore the associated risk factors of symptomatic knee osteonecrosis (KON) in patients with systemic lupus erythematosus (SLE), we conducted a retrospective case-control study to compare the clinical and laboratory features between SLE patients with and without symptomatic KON matched by age and gender. Univariate and multivariate regression analyses were used to evaluate possible associated risk factors. Twenty (one male, nineteen females) out of 3941 lupus patients were identified as symptomatic KON, which was confirmed by magnetic resonance imaging. The mean age at KON onset was 34.4 (range 12-67) years, and the median course of lupus at KON onset was 72.5 (range 8-123) months. Univariate and multivariate analyses identified that the prevalence of cutaneous vasculitis (OR 5.23; 95 % CI 1.11-24.70), hyperfibrinogenemia (OR 4.75; 95 % CI 1.08-20.85), and elevated IgG levels (OR 6.05; 95 % CI 1.58-23.16) were statistically higher in KON group, and hydroxychloroquine (HCQ) usage was statistically lower in KON group (OR 0.27; 95 % CI 0.07-0.97). Glucocorticoid usage, in terms of maximal dose, duration of treatment, and the percentage of receiving methylprednisolone pulse therapy, did not show statistical difference between the two groups (p > 0.05). Symptomatic KON is a relatively rare complication of SLE. Cutaneous vasculitis, hyperfibrinogenemia, and elevated IgG levels are possible risk factors, whereas HCQ may provide a protective effect. Our results suggest that lupus activity as well as hypercoagulation status may play a role in the pathogenesis of KON in lupus. PMID:27230994

  19. Multiplexing of miniaturized planar antibody arrays for serum protein profiling--a biomarker discovery in SLE nephritis.

    PubMed

    Petersson, Linn; Dexlin-Mellby, Linda; Bengtsson, Anders A; Sturfelt, Gunnar; Borrebaeck, Carl A K; Wingren, Christer

    2014-06-01

    In the quest to decipher disease-associated biomarkers, miniaturized and multiplexed antibody arrays may play a central role in generating protein expression profiles, or protein maps, of crude serum samples. In this conceptual study, we explored a novel, 4-times larger pen design, enabling us to, in a unique manner, simultaneously print 48 different reagents (antibodies) as individual 78.5 μm(2) (10 μm in diameter) sized spots at a density of 38,000 spots cm(-2) using dip-pen nanolithography technology. The antibody array set-up was interfaced with a high-resolution fluorescent-based scanner for sensitive sensing. The performance and applicability of this novel 48-plex recombinant antibody array platform design was demonstrated in a first clinical application targeting SLE nephritis, a severe chronic autoimmune connective tissue disorder, as the model disease. To this end, crude, directly biotinylated serum samples were targeted. The results showed that the miniaturized and multiplexed array platform displayed adequate performance, and that SLE-associated serum biomarker panels reflecting the disease process could be deciphered, outlining the use of miniaturized antibody arrays for disease proteomics and biomarker discovery. PMID:24763547