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Sample records for active lupus nephritis

  1. Lupus nephritis

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000481.htm Lupus nephritis To use the sharing features on this page, please enable JavaScript. Lupus nephritis is a kidney disorder which is a complication ...

  2. Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

    PubMed Central

    Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

    1978-01-01

    Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

  3. Lupus nephritis: an update.

    PubMed

    Imran, Tasnim F; Yick, Frederick; Verma, Suneet; Estiverne, Christopher; Ogbonnaya-Odor, Chinonye; Thiruvarudsothy, Srikanth; Reddi, Alluru S; Kothari, Neil

    2016-02-01

    Lupus nephritis (LN) is an inflammatory condition of the kidneys that encompasses various patterns of renal disease including glomerular and tubulointerstitial pathology. It is a major predictor of poor prognosis in patients with systemic lupus erythematosus (SLE). Genetic factors, including several predisposing loci, and environmental factors, such as EBV and ultraviolet light, have been implicated in the pathogenesis. It carries a high morbidity and mortality if left untreated. Renal biopsy findings are utilized to guide treatment. Optimizing risk factors such as proteinuria and hypertension with renin-angiotensin receptor blockade is crucial. Immunosuppressive therapy is recommended for patients with focal or diffuse proliferative lupus nephritis (Class III or IV) disease, and certain patients with membranous LN (Class V) disease. Over the past decade, immunosuppressive therapies have significantly improved long-term outcomes, but the optimal therapy for LN remains to be elucidated. Cyclophosphamide-based regimens, given concomitantly with corticosteroids, have improved survival significantly. Even though many patients achieve remission, the risk of relapse remains considerably high. Other treatments include hydroxychloroquine, mycofenolate mofetil, and biologic therapies such as Belimumab, Rituximab, and Abatacept. In this paper, we provide a review of LN, including pathogenesis, classification, and clinical manifestations. We will focus, though, on discussion of the established as well as emerging therapies for patients with proliferative and membranous lupus nephritis. PMID:26471017

  4. 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

  5. Prognostic factors in lupus nephritis.

    PubMed

    Mok, C C

    2005-01-01

    Systemic lupus erythematosus (SLE) is a heterogeneous disorder and its renal manifestations are protean. The course and prognosis of lupus nephritis is dependent on a large number of demographic, histopathological, serological, racial, socioeconomic and time dependent factors. Moreover, the initial and maintenance therapeutic regimens may also influence the long term renal outcome. This article reviews the important prognostic factors that have been reported in literature. The management strategy of lupus nephritis should be individualized and based on a composite of these parameters. PMID:15732286

  6. Lupus nephritis management guidelines compared.

    PubMed

    Wilhelmus, Suzanne; Bajema, Ingeborg M; Bertsias, George K; Boumpas, Dimitrios T; Gordon, Caroline; Lightstone, Liz; Tesar, Vladimir; Jayne, David R

    2016-06-01

    In the past years, many (randomized) trials have been performed comparing the treatment strategies for lupus nephritis. In 2012, these data were incorporated in six different guidelines for treating lupus nephritis. These guidelines are European, American and internationally based, with one separate guideline for children. They offer information on different aspects of the management of lupus nephritis including induction and maintenance treatment of the different histological classes, adjunctive treatment, monitoring of the patient, definitions of response and relapse, indications for (repeat) renal biopsy, and additional challenges such as the presence of vascular complications, the pregnant SLE patient, treatment in children and adolescents and considerations about end-stage renal disease and transplantation. In this review, we summarize the guidelines, determine the common ground between them, highlight the differences and discuss recent literature. PMID:25920920

  7. ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

    PubMed Central

    Caster, Dawn J.; Korte, Erik A.; Nanda, Sambit K.; McLeish, Kenneth R.; Oliver, Rebecca K.; G'Sell, Rachel T.; Sheehan, Ryan M.; Freeman, Darrell W.; Coventry, Susan C.; Kelly, Jennifer A.; Guthridge, Joel M.; James, Judith A.; Sivils, Kathy L.; Alarcon-Riquelme, Marta E.; Scofield, R. Hal; Adrianto, Indra; Gaffney, Patrick M.; Stevens, Anne M.; Freedman, Barry I.; Langefeld, Carl D.; Tsao, Betty P.; Pons-Estel, Bernardo A.; Jacob, Chaim O.; Kamen, Diane L.; Gilkeson, Gary S.; Brown, Elizabeth E.; Alarcon, Graciela S.; Edberg, Jeffrey C.; Kimberly, Robert P.; Martin, Javier; Merrill, Joan T.; Harley, John B.; Kaufman, Kenneth M.; Reveille, John D.; Anaya, Juan-Manuel; Criswell, Lindsey A.; Vila, Luis M.; Petri, Michelle; Ramsey-Goldman, Rosalind; Bae, Sang-Cheol; Boackle, Susan A.; Vyse, Timothy J.; Niewold, Timothy B.; Cohen, Philip

    2013-01-01

    The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity. PMID:23970121

  8. Pro: Cyclophosphamide in lupus nephritis.

    PubMed

    Kallenberg, Cees G M

    2016-07-01

    Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up data available for low-dose pulse cyclophosphamide, the fact that compliance is guaranteed with this regimen and economic issues all favour the Euro-Lupus regimen in this author's opinion. For maintenance treatment, either azathioprine (AZA) or MMF may be used; AZA is preferred in case pregnancy is planned, while MMF is preferred when the disease relapses during use of AZA and, possibly, after successful induction of remission with MMF. PMID:27190359

  9. 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

  10. Rethinking biologics in lupus nephritis.

    PubMed

    Venuturupalli, S

    2016-09-01

    Lupus nephritis (LN) is a chronic and devastating complication of systemic lupus erythematosus. Despite advances in our understanding of LN and the availability of effective therapies, LN remains a difficult clinical problem, and progression to end stage renal disease remains a significant challenge. Though the advent of biologics has revolutionized the treatment of many rheumatological conditions, and several clinical trials of biologics have been conducted in LN, the promise of biologics remains unfulfilled. The experience gained from these initial clinical trials can help tailor approaches in future clinical trials, and the lessons learned can be applied to find a cure for this condition. PMID:27497255

  11. IL10 in Lupus Nephritis: Detection and relationship with disease activity

    PubMed Central

    Zeid, Sameh Abou; Khalifa, Ghada; Nabil, Malak

    2015-01-01

    Introduction Glomerulonephritis is a major determinant of the course and prognosis of systemic lupus erythematosus (SLE) and is evident in 40%–85% of patients. IL10, a cytokine produced by monocytes and-to a lesser extent-lymphocytes, has pleiotropic effects in immune regulation and inflammation. It enhances B cell survival, proliferation, differentiation, and antibody production; these effects play a role in autoimmune diseases. Among identified polymorphisms in the IL10 promoter, three linked single nucleotide polymorphisms (SNPs) of −1082 G/A, 819 T/C, and −592 A/C have been shown to influence the IL10 gene expression. Compared with the −592 C allele, the 592 A is associated with lower IL10 production in vitro. The objectives of this study were to investigate the −592 A/C polymorphism in patients with and without lupus nephritis and to assess its influence on IL10 secretion in vivo and its role in pathogenesis and clinicopathological characteristics of lupus nephritis. Methods This case control study was conducted on 40 SLE patients recruited for the study from those attending the nephrology department of the Theodor Bilharz Research Institute (outpatient clinic and inpatient ward) in 2013. Patients were divided into two groups, group I (SLE patients without evidence of nephritis) and group II (SLE patients with lupus nephritis). Data were analyzed using SPSS (version 12), a t-test, Chi square, ANOVA, and the Pearson product–moment correlation coefficient. Results Our study found an increase in IL10 serum in lupus nephritis patients compared to those without renal involvement (without statistical significance). No significant differences emerged in the level of IL10 serum among different pathological classes. Conclusion The IL10 gene (−592 A/C) polymorphism, though not associated with lupus nephritis’s susceptibility in the present study, does play a role. PMID:26816594

  12. 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

  13. Antiphospholipid Antibodies in Lupus Nephritis.

    PubMed

    Parodis, Ioannis; Arnaud, Laurent; Gerhardsson, Jakob; Zickert, Agneta; Sundelin, Birgitta; Malmström, Vivianne; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-01-01

    Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). It remains unclear whether antiphospholipid antibodies (aPL) alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204) or without (n = 294) LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous), before and after induction treatment (short-term outcomes). Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease (CKD) stage, after a median follow-up of 11.3 years (range: 3.3-18.8). Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all), but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1-2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are affected by

  14. Antiphospholipid Antibodies in Lupus Nephritis

    PubMed Central

    Arnaud, Laurent; Gerhardsson, Jakob; Zickert, Agneta; Sundelin, Birgitta; Malmström, Vivianne; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-01-01

    Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). It remains unclear whether antiphospholipid antibodies (aPL) alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204) or without (n = 294) LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous), before and after induction treatment (short-term outcomes). Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease (CKD) stage, after a median follow-up of 11.3 years (range: 3.3–18.8). Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all), but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1–2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are affected by

  15. Moderator's view: Cyclophosphamide in lupus nephritis.

    PubMed

    Tesar, Vladimir

    2016-07-01

    Mycophenolate mofetil was recently accepted as the effective induction treatment of lupus nephritis, with the potential to replace cyclophosphamide or at least expand our therapeutic armamentarium in patients with this lifelong disease often requiring repeated induction treatment of its relapses. Compared with cyclophosphamide, mycophenolate may be more effective in black patients, and the risk of gonadotoxicity may be significantly lower in mycophenolate-treated subjects. However, experience with mycophenolate in severe lupus nephritis is still limited and we also have insufficient data on the long-term outcome of mycophenolate-treated patients. Treatment with mycophenolate is more expensive than with cyclophosphamide, which may limit its use, especially in low- and middle-income countries. The efficacy of mycophenolate mofetil may be more dependent on the patient's compliance compared with intravenous cyclophosphamide pulses. Low-dose cyclophosphamide remains an effective and relatively safe induction treatment of active lupus nephritis, but to decrease its cumulative toxicity, repeated exposure to cyclophosphamide in relapsing patients should be (if possible) avoided. PMID:27190357

  16. Lupus Nephritis: The Evolving Role of Novel Therapeutics

    PubMed Central

    Rovin, Brad H.; Parikh, Samir V.

    2014-01-01

    Immune complex accumulation in the kidney is the hallmark of lupus nephritis and triggers a series of events that result in kidney inflammation and injury. Cytotoxic agents and corticosteroids are standard of care for lupus nephritis treatment, but are associated with considerable morbidity and suboptimal outcomes. Recently, there has been interest in using novel biologic agents and small molecules to treat lupus nephritis. These therapies can be broadly categorized as anti-inflammatory (laquinamod, anti–tumor necrosis factor–like weak inducer of apotosis, anti-C5, and retinoids), antiautoimmunity (anti-CD20, anti–interferon α, and costimulatory blockers), or both (anti–interleukin 6 and proteasome inhibitors). Recent lupus nephritis clinical trials applied biologics or small molecules of any category to induction treatment, seeking short-term end points of complete renal response. These trials in general have not succeeded. When lupus nephritis comes to clinical attention during the inflammatory stage of the disease, the autoimmune stage leading to kidney inflammation will have been active for some time. The optimal approach for using novel therapies may be to initially target kidney inflammation to preserve renal parenchyma, followed by suppression of autoimmunity. In this review, we discuss novel lupus nephritis therapies and how they fit into a combinatorial treatment strategy based on the pathogenic stage. PMID:24411715

  17. Do we still need renal biopsy in lupus nephritis?

    PubMed Central

    Cervera, Ricard

    2016-01-01

    The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment. PMID:27407281

  18. Increased urinary excretion of platelet activating factor in mice with lupus nephritis

    SciTech Connect

    Macconi, D.; Noris, M.; Benfenati, E.; Quaglia, R.; Pagliarino, G. ); Remuzzi, G. Ospedali Riuniti di Bergamo )

    1991-01-01

    Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-(1{prime},2{prime}-{sup 3}H)alkyl) is filtered through the glomerulus and excreted in the urine. The results show that: (1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, (2) PAF levels increased when animals started to develop high grade proteinuria, (3) after intravenous injection of ({sup 3}H) PAF In nephritic mice, a negligible amount of ({sup 3}H) ether lipid, corresponding to ({sup 3}H)1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.

  19. Lupus Nephritis: An Overview of Recent Findings

    PubMed Central

    de Zubiria Salgado, Alberto; Herrera-Diaz, Catalina

    2012-01-01

    Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. In susceptible individuals suffering of SLE, in situ formation and deposit of immune complexes (ICs) from apoptotic bodies occur in the kidneys as a result of an amplified epitope immunological response. IC glomerular deposits generate release of proinflammatory cytokines and cell adhesion molecules causing inflammation. This leads to monocytes and polymorphonuclear cells chemotaxis. Subsequent release of proteases generates endothelial injury and mesangial proliferation. Presence of ICs promotes adaptive immune response and causes dendritic cells to release type I interferon. This induces maturation and activation of infiltrating T cells, and amplification of Th2, Th1 and Th17 lymphocytes. Each of them, amplify B cells and activates macrophages to release more proinflammatory molecules, generating effector cells that cannot be modulated promoting kidney epithelial proliferation and fibrosis. Herein immunopathological findings of LN are reviewed. PMID:22536486

  20. The Role of Autophagy in Lupus Nephritis.

    PubMed

    Wang, Linlin; Law, Helen Ka Wai

    2015-01-01

    Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by the generation of immune responses to self-antigens. Lupus nephritis is one of the most common and severe complications in SLE patients. Though the pathogenesis of lupus nephritis has been studied extensively, unresolved questions are still left and new therapeutic methods are needed for disease control. Autophagy is a conserved catabolic process through which cytoplasmic constituents can be degraded in lysosome and reused. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In particular, autophagy can affect almost all parts of the immune system and is involved in autoimmune diseases. Based on genetic analysis, cell biology, and mechanism studies of the classic and innovative therapeutic drugs, there are growing lines of evidence suggesting the relationship between autophagy and lupus nephritis. In the present review, we summarize the recent publications investigating the relationship between autophagy and lupus nephritis and provide a new perspective towards the pathogenesis of lupus nephritis. PMID:26506346

  1. The Role of Autophagy in Lupus Nephritis

    PubMed Central

    Wang, Linlin; Law, Helen Ka Wai

    2015-01-01

    Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by the generation of immune responses to self-antigens. Lupus nephritis is one of the most common and severe complications in SLE patients. Though the pathogenesis of lupus nephritis has been studied extensively, unresolved questions are still left and new therapeutic methods are needed for disease control. Autophagy is a conserved catabolic process through which cytoplasmic constituents can be degraded in lysosome and reused. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In particular, autophagy can affect almost all parts of the immune system and is involved in autoimmune diseases. Based on genetic analysis, cell biology, and mechanism studies of the classic and innovative therapeutic drugs, there are growing lines of evidence suggesting the relationship between autophagy and lupus nephritis. In the present review, we summarize the recent publications investigating the relationship between autophagy and lupus nephritis and provide a new perspective towards the pathogenesis of lupus nephritis. PMID:26506346

  2. The persistent challenge of lupus nephritis.

    PubMed

    Valesini, Guido; Conti, Fabrizio

    2011-06-01

    Systemic lupus erythematosus has long been considered the prototypic autoimmune disease. Although the etiology remains enigmatic, there has been vigorous definition of the clinical features and the natural history. In this issue, we review the persistent challenge of lupus nephritis and, in particular, features of diagnosis as well as treatment options. It is clear that major therapeutic advances have occurred but there is still a considerable unmet need in the population. This issue does not review all the clinical problems of lupus nephritis, but rather attempts to place the most recent data in perspective for the clinician. PMID:20811786

  3. Natural history of "silent" lupus nephritis.

    PubMed

    Bennett, W M; Bardana, E J; Norman, D J; Houghton, D C

    1982-05-01

    Twenty patients with systemic lupus erythematosus but without evident renal involvement previously underwent percutaneous renal biopsy. Findings revealed almost universal pathologic evidence of nephritis. Included were three patients who had diffuse proliferative changes and five who had subendothelial electron dense deposits. Only four patients developed clinical renal disease during the follow-up period while no patient died or required dialysis. Using the Life Table Method, the cumulative percentage of patients free from any clinical renal disease was over 60% at 10 yr from the time of diagnosis of systemic lupus, and at 8 yr from the time of the original biopsy. It is concluded that silent lupus nephritis, regardless of histologic subtype, has a favorable prognosis. These data may not be applicable to patients with similar biopsies who have evidence of clinical lupus nephritis. PMID:7091151

  4. Novel Autoantigens Associated with Lupus Nephritis

    PubMed Central

    Onishi, Sachiko; Adnan, Endy; Ishizaki, Jun; Miyazaki, Tatsuhiko; Tanaka, Yuki; Matsumoto, Takuya; Suemori, Koichiro; Shudou, Masachika; Okura, Takafumi; Takeda, Hiroyuki; Sawasaki, Tatsuya; Yasukawa, Masaki; Hasegawa, Hitoshi

    2015-01-01

    Systemic lupus erythematosus (SLE) is characterized by production of a variety of autoantibodies. Although anti-double-stranded DNA (anti-dsDNA) antibodies contribute to the pathogenesis of lupus nephritis (LN), they are not sufficient for diagnosis and evaluation of disease activity. To obtain other autoantibodies associated with LN, we screened autoantigens reacting with the sera of LN patients by using an N-terminal biotinylated protein library created from a wheat cell-free protein production system. We screened 17 proteins that showed higher positive signals in the active phase than in the inactive phase of SLE, and higher positive signals in the serum of SLE patient with nephritis than in that of patient without nephritis. Of these, two LN-associated autoantigens, ribosomal RNA-processing protein 8 (RRP8) and spermatid nuclear transition protein 1 (TNP1) were identified by immunoprecipitation and immunofluorescence of renal tissues. Circulating anti-RRP8 and anti-TNP1 autoantibodies were recognized and deposited as an immune complex (IC) in glomeruli. IC was deposited preferentially in glomeruli rather than in other organs in C57BL/6 mice injected with RRP8 or TNP1. ELISA analysis of sera from patients with various rheumatic diseases demonstrated reactivity for RRP8 and TNP1 in 20% and 14.7% of SLE patients, respectively, whereas there was little or no reactivity in patients with other rheumatic diseases. Among SLE patients, 63.6% and 45.5% of those with LN were positive for anti-RRP8 and anti-TNP1 antibodies, compared with 12.5% and 9.4% of SLE patients without nephritis, respectively. Both proteins are cationic, and their respective antibodies did not cross-react with dsDNA. These proteins released from apoptotic cells form ICs with each autoantibody, and their ICs may become trapped at anionic sites in the glomerular basement membrane, leading to deposition in glomeruli. These autoantibodies may be useful for prediction of LN in subsets of SLE patients who

  5. A case of PRES in an active lupus nephritis patient after treatment of corticosteroid and cyclophosphamide.

    PubMed

    Jabrane, M; Ait Lahcen, Z; Fadili, W; Laouad, I

    2015-05-01

    Posterior reversible encephalopathy syndrome (PRES) is primarily a radiological diagnosis. The syndrome is characterized by headache, altered mental status, seizures, and bilateral posterior white matter edema in a nonvascular distribution on neuroimaging with resolution of findings usually in 7-14 days (Casey et al. in AJNR Am J Neuroradiol 21:1199-1206, 2000). In most cases, computed tomography of the brain will show hypodense lesions in the parieto-occipital lobe. Although this syndrome is uncommon, prompt and accurate recognition allows early treatment, which has been shown to produce favorable outcomes. It is hypothesized that the dysfunction can be caused by a failure of autoregulation systemic hypertension or by the cytotoxic effects of vasculitides and immunosuppressive drugs. The present report is a possible second case of cyclophosphamide-induced PRES in a 16-year-old girl with systemic lupus erythematous and lupus nephritis. The initial suspected diagnosis was an ischemic stroke, but it was later changed, with resolution of symptoms after management of the underlying cause. PMID:25387825

  6. Ofatumumab treatment in lupus nephritis patients.

    PubMed

    Haarhaus, Malena Loberg; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-08-01

    Rituximab is frequently used in systemic lupus erythematosus; however, side effects such as infusion-related reactions limit its use. In this case report, we describe, for the first time, treatment with ofatumumab in four patients with lupus nephritis. The treatment was well tolerated in three of the patients, and a reduction of proteinuria was seen in all cases. This emphasizes the importance of alternative B-cell-depleting therapies in patients with an initial good response to rituximab, but who develop side effects. PMID:27478595

  7. Ofatumumab treatment in lupus nephritis patients

    PubMed Central

    Haarhaus, Malena Loberg; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-01-01

    Rituximab is frequently used in systemic lupus erythematosus; however, side effects such as infusion-related reactions limit its use. In this case report, we describe, for the first time, treatment with ofatumumab in four patients with lupus nephritis. The treatment was well tolerated in three of the patients, and a reduction of proteinuria was seen in all cases. This emphasizes the importance of alternative B-cell-depleting therapies in patients with an initial good response to rituximab, but who develop side effects. PMID:27478595

  8. Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus

    PubMed Central

    Elshikha, Ahmed S.; Lu, Yuanqing; Chen, Mong-Jen; Akbar, Mohammad; Zeumer, Leilani; Ritter, Andrea; Elghamry, Hanaa; Mahdi, Mahmoud A.; Morel, Laurence; Song, Sihong

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans. PMID:27232337

  9. Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus.

    PubMed

    Elshikha, Ahmed S; Lu, Yuanqing; Chen, Mong-Jen; Akbar, Mohammad; Zeumer, Leilani; Ritter, Andrea; Elghamry, Hanaa; Mahdi, Mahmoud A; Morel, Laurence; Song, Sihong

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans. PMID:27232337

  10. Lupus Nephritis: Glycogen Synthase Kinase 3β Promotion of Renal Damage Through Activation of the NLRP3 Inflammasome in Lupus-Prone Mice

    PubMed Central

    Zhao, Jijun; Wang, Hongyue; Huang, Yuefang; Zhang, Hui; Wang, Shuang; Gaskin, Felicia; Yang, Niansheng; Fu, Shu Man

    2015-01-01

    Objective Glycogen synthase kinase 3β (GSK-3β) has been demonstrated to be involved in immune and inflammatory responses via multiple signaling pathways, leading to the production of proinflammatory cytokines. The purpose of this study was to investigate the role of GSK-3β in the pathogenesis of lupus nephritis in 2 mouse models. Methods Thiadiazolidinone 8 (TDZD-8), a selective inhibitor of GSK-3β, was administered intraperitoneally to 12-week-old MRL/lpr mice for 8 weeks or to 22-week-old (NZB × NZW)F1 mice for 12 weeks. The expression of GSK-3β and NLRP3 inflammasome components was analyzed. Proteinuria, biochemical parameters, proinflammatory cytokines, anti–double-stranded DNA (anti-dsDNA) antibody levels, and renal pathology were examined. In vitro, the effect of GSK-3β–directed small interfering RNA (siRNA) on NLRP3 inflammasome activation was evaluated in bone marrow–derived macrophages (BMMs) from the mice and in the J774A.1 macrophage cell line. Results The incidence of severe proteinuria and renal inflammation was significantly attenuated in both models, with a significant reduction in anti-dsDNA antibody production, immune complex deposition in the kidney, and circulating proinflammatory cytokine levels. TDZD-8 inhibited the activation of GSK-3β and caspase 1, with a concomitant decrease in interleukin-1β (IL-1β) synthesis. In vitro, GSK-3β siRNA transfection of mouse BMMs and the J774A.1 cell line with GSK-3β siRNA inhibited the expression of GSK-3β, the activation of caspase 1, and the production of IL-1β. Conclusion These results show that GSK-3β promotes lupus nephritis at least partly by activating the NLRP3/IL-1β pathway. The linking of GSK-3β to the NLRP3/IL-1β pathway is a novel observation in our study. Our results suggest that the GSK-3β/NLRP3/IL-1β pathway may be a potential therapeutic target for lupus in humans. PMID:25512114

  11. Appraisal of lupus nephritis by renal imaging with gallium-67

    SciTech Connect

    Bakir, A.A.; Lopez-Majano, V.; Hryhorczuk, D.O.; Rhee, H.L.; Dunea, G.

    1985-08-01

    To assess the activity of lupus nephritis, 43 patients with systemic lupus erythematosus (SLE) were studied by gallium imaging. Delayed renal visualization 48 hours after the gallium injection, a positive result, was noted in 25 of 48 scans. Active renal disease was defined by the presence of hematuria, pyuria (10 or more red blood cells or white blood cells per high-power field), proteinuria (1 g or more per 24 hours), a rising serum creatinine level, or a recent biopsy specimen showing proliferative and/or necrotizing lesions involving more than 20 percent of glomeruli. Renal disease was active in 18 instances, inactive in 23, and undetermined in seven (a total of 48 scans). Sixteen of the 18 scans (89 percent) in patients with active renal disease showed positive findings, as compared with only four of 23 scans (17 percent) in patients with inactive renal disease (p less than 0.001). Patients with positive scanning results had a higher rate of hypertension (p = 0.02), nephrotic proteinuria (p = 0.01), and progressive renal failure (p = 0.02). Mild mesangial nephritis (World Health Organization classes I and II) was noted only in the patients with negative scanning results (p = 0.02) who, however, showed a higher incidence of severe extrarenal SLE (p = 0.04). It is concluded that gallium imaging is a useful tool in evaluating the activity of lupus nephritis.

  12. A20 overexpression alleviates pristine-induced lupus nephritis by inhibiting the NF-κB and NLRP3 inflammasome activation in macrophages of mice

    PubMed Central

    Li, Min; Shi, Xiaowei; Qian, Tian; Li, Jian; Tian, Zhiqiang; Ni, Bing; Hao, Fei

    2015-01-01

    Background: Lupus nephritis is an autoimmune inflammatory disease and urgently needs effective anti-inflammation therapies. A20, tumor necrosis factor alpha induced protein 3 (TNFAIP3), is a key negative regulator of inflammation, however whether A20 can regulate lupus nephritis has not been clarified. This study aimed at investigating the potential therapeutic effect of A20 on renal inflammation in mouse pristine model oflupus. Methodology/Principal Findings: Female BALB/c mice were intraperitoneally injected with pristine to establish lupus renal injury. The levels of serum IL-1β, IL-6 and autoantibodies and the degrees of renal injury and CCL2 and F4/80 levels were measured. The levels of the NF-κB and NLRP3 inflammasome activation in peritoneal macrophages were determined. We found that injection with pristine increased the levels of serum IL-1β, IL-6, autoantibodies and CCL20 and F4/80 expression in the kidney and induced renal injury, accompanied by enhancing the NF-κB and NLRP3 inflammasome activation in macrophages of mice. In contrast, treatment with Ad-A20, but not with Ad-control, significantly mitigated pristine-induced inflammatory responses and renal injury,and reduced the NF-κB and NLRP3 inflammasome activation in macrophages in mice. Conclusion/Significance: Our data indicated that induction of A20 overexpression inhibited pristane induced lupus inflammation and renal injury in mice and may be a new therapeutic strategy for treatment of lupus nephritis. PMID:26770333

  13. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

    SYNOPSIS Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that mycophenolate mofetil may be similar to quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil. PMID:25034160

  14. Obstetric nephrology: lupus and lupus nephritis in pregnancy.

    PubMed

    Stanhope, Todd J; White, Wendy M; Moder, Kevin G; Smyth, Andrew; Garovic, Vesna D

    2012-12-01

    SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancy-related complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy. PMID:22879437

  15. The Value of a Panel of Autoantibodies for Predicting the Activity of Lupus Nephritis at Time of Renal Biopsy

    PubMed Central

    Moroni, Gabriella; Quaglini, Silvana; Radice, Antonella; Trezzi, Barbara; Raffiotta, Francesca; Messa, Piergiorgio; Sinico, Renato Alberto

    2015-01-01

    Few studies have correlated serum biomarkers with renal histology, the gold standard for renal activity, in lupus nephritis (LN). We tested a panel of autoantibodies and complement at the time of kidney biopsy and after treatment. Anti-dsDNA, anti-nucleosome, anti-ribosome P, and anti-C1q antibodies and C3/C4 were measured in 107 patients with LN at the time of renal biopsy and after 6–12 months and were correlated with clinical/histological parameters. At multivariate analysis, high titers of anti-C1q antibodies or of anti-dsDNA antibodies (P = 0.005, OR = 8.67, CI: 2.03–37.3) were the independent predictors that discriminate proliferative from nonproliferative LN. All the immunological parameters, except anti-ribosome, showed a significant correlation with activity index but not with chronicity index. Only anti-C1q showed a significant correlation with the amount of proteinuria (R = 0.2, P = 0.03). None of the immunological parameters were predictive of remission at 6 and 12 months. We found that anti-C1q alone or in combination with anti-dsDNA emerged as the most reliable test in differentiating proliferative and nonproliferative LN. Anti-C1q was the only test correlated with the clinical presentation of LN. After treatment, the titre of the autoantibodies was significantly reduced, but none was predictive of remission. PMID:25815344

  16. The value of a panel of autoantibodies for predicting the activity of lupus nephritis at time of renal biopsy.

    PubMed

    Moroni, Gabriella; Quaglini, Silvana; Radice, Antonella; Trezzi, Barbara; Raffiotta, Francesca; Messa, Piergiorgio; Sinico, Renato Alberto

    2015-01-01

    Few studies have correlated serum biomarkers with renal histology, the gold standard for renal activity, in lupus nephritis (LN). We tested a panel of autoantibodies and complement at the time of kidney biopsy and after treatment. Anti-dsDNA, anti-nucleosome, anti-ribosome P, and anti-C1q antibodies and C3/C4 were measured in 107 patients with LN at the time of renal biopsy and after 6-12 months and were correlated with clinical/histological parameters. At multivariate analysis, high titers of anti-C1q antibodies or of anti-dsDNA antibodies (P = 0.005, OR = 8.67, CI: 2.03-37.3) were the independent predictors that discriminate proliferative from nonproliferative LN. All the immunological parameters, except anti-ribosome, showed a significant correlation with activity index but not with chronicity index. Only anti-C1q showed a significant correlation with the amount of proteinuria (R = 0.2, P = 0.03). None of the immunological parameters were predictive of remission at 6 and 12 months. We found that anti-C1q alone or in combination with anti-dsDNA emerged as the most reliable test in differentiating proliferative and nonproliferative LN. Anti-C1q was the only test correlated with the clinical presentation of LN. After treatment, the titre of the autoantibodies was significantly reduced, but none was predictive of remission. PMID:25815344

  17. Con: Cyclophosphamide for the treatment of lupus nephritis.

    PubMed

    Mok, Chi Chiu

    2016-07-01

    Kidney involvement is a major determinant for morbidity and mortality in patients with systemic lupus erythematosus. The treatment target of lupus renal disease is to induce and maintain remission and to minimize disease or treatment-related comorbidities. Cyclophosphamide (CYC), in conjunction with glucocorticoids, has conventionally been used for the initial treatment of lupus nephritis. However, the major concerns of CYC are its toxicities, such as infertility, urotoxicity and oncogenicity, which are particularly relevant in women of childbearing age. As a result, maintenance therapy of lupus nephritis with an extended course of CYC pulses has largely been replaced by other immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine. Recent randomized controlled trials have demonstrated non-inferiority of MMF to pulse CYC as induction therapy of lupus nephritis. Although MMF as induction-maintenance therapy has been increasingly used in lupus nephritis, its efficacy in the long-term preservation of renal function remains to be elucidated. MMF is not necessarily less toxic than CYC. Meta-analyses of clinical trials show similar incidence of infective complications and gastrointestinal adverse events in both MMF- and CYC-based regimens. However, considering the reduction in gonadal toxicity and the risk of oncogenicity, MMF may be used as first-line therapy of lupus nephritis. Tacrolimus (TAC) has recently been shown to be equivalent to either MMF or CYC for inducing remission of lupus nephritis and may be considered as another non-CYC alternative. Combined low-dose MMF and TAC appears to be more effective than CYC pulses in Chinese patients with lupus nephritis and has the potential to replace the more toxic CYC regimens in high-risk patients. Currently, CYC still plays an important role in the management of lupus nephritis patients with impaired or rapidly deteriorating renal function, crescentic glomerulonephritis or as salvage therapy for

  18. Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation.

    PubMed

    Zhao, Jijun; Zhang, Hui; Huang, Yuefang; Wang, Hongyue; Wang, Shuang; Zhao, Chunmei; Liang, Yingjie; Yang, Niansheng

    2013-09-01

    Nuclear factor-kappa B (NF-κB) and NLRP3 inflammasome are involved in inflammation and autoimmunity. In vitro data have shown that Bay11-7082 selectively inhibits NLRP3 inflammasome activity independent of NF-κB activity. In this study, we evaluated the therapeutic effects of Bay11-7082 on murine lupus nephritis (LN) in vivo. Twelve-week-old MRL/lpr mice were treated with either Bay11-7082 (5mg/kg) or vehicle (DMSO/PBS buffer) by intraperitoneal injection thrice per week for 8 weeks. NLRP3 inflammasome formation and NF-κB activation were measured. Histopathology, immune complex deposits, proteinuria, renal function and production of anti-dsDNA antibody as well as inflammatory markers were evaluated. Bay11-7082 treatment inhibited renal NLRP3 inflammasome formation and NF-κB activation in vivo. Bay11-7082 decreased proteinuria, blood urea nitrogen, resulting in dramatically attenuated renal damage. Bay11-7082-treated mice had decreased serum anti-dsDNA level and less renal immune complex deposition. The IL-1β, TNF-α and chemokine (C-C Motif) ligand 2 (CCL2) levels and infiltration of macrophages as well as the mortality were significantly reduced by Bay11-7082 treatment. This study suggests that dual inhibition of NLRP3 inflammasome and NF-κB activation using Bay11-7082 or its analogues may be a promising therapeutic strategy for preventing the progression of LN. PMID:23770281

  19. A diagnostic dilemma: lupus nephritis or renal polyarteritis nodosa?

    PubMed

    Bhushan, Shashi; Abreo, Kenneth; Rodziewicz, Natalie; Gu, Xin; Singh, Neeraj

    2016-07-01

    Lupus nephritis and renal polyarteritis nodosa (PAN) are two distinct disorders that rarely overlap. Herein, we describe a patient who was initially diagnosed with lupus nephritis based on her clinical presentation, proteinuria, hematuria, positive anti-nuclear antibody, and a kidney biopsy. A month later, the patient presented with left flank pain and weakness. A CT scan of the abdomen and pelvis showed a perinephric hematoma and the renal arteriogram revealed numerous microaneurysms within the kidney consistent with renal PAN. This case elucidates the diagnostic and management dilemmas that confront physicians taking care of patients with overlapping features of lupus nephritis and renal PAN and also points to the possible role of lupus nephritis in pathogenesis of renal PAN. PMID:27055352

  20. Intravenous Immunoglobulin in the Management of Lupus Nephritis

    PubMed Central

    Wenderfer, Scott E.; Thacker, Trisha

    2012-01-01

    The occurrence of nephritis in patients with systemic lupus erythematosus is associated with increased morbidity and mortality. The pathogenesis of lupus nephritis is complex, involving innate and adaptive cellular and humoral immune responses. Autoantibodies in particular have been shown to be critical in the initiation and progression of renal injury, via interactions with both Fc-receptors and complement. One approach in the management of patients with lupus nephritis has been the use of intravenous immunoglobulin. This therapy has shown benefit in the setting of many forms of autoantibody-mediated injury; however, the mechanisms of efficacy are not fully understood. In this paper, the data supporting the use of immunoglobulin therapy in lupus nephritis will be evaluated. In addition, the potential mechanisms of action will be discussed with respect to the known involvement of complement and Fc-receptors in the kidney parenchyma. Results are provocative and warrant additional clinical trials. PMID:23056926

  1. Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies

    PubMed Central

    Yung, Susan; Chan, Tak Mao

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortality that affects over half of the SLE population during the course of disease. The etiology of lupus nephritis is multifactorial and remains to be fully elucidated. Accumulating evidence suggests that in addition to forming immune complexes and triggering complement activation, anti-dsDNA antibodies contribute to the pathogenesis of lupus nephritis through binding, either directly or indirectly, to cross-reactive antigens or chromatin materials, respectively, to resident renal cells and/or extracellular matrix components, thereby triggering downstream cellular activation and proliferation as well as inflammatory and fibrotic processes. Several cross-reactive antigens that mediate anti-dsDNA antibody binding have been identified, such as annexin II and alpha-actinin. This review discusses the mechanisms through which anti-dsDNA antibodies contribute to immunopathogenesis in lupus nephritis. Corticosteroids combined with either mycophenolic acid (MPA) or cyclophosphamide is the current standard of care immunosuppressive therapy for severe lupus nephritis. This review also discusses recent data showing distinct effects of MPA and cyclophosphamide on inflammatory and fibrotic processes in resident renal cells. PMID:26441980

  2. Glomerular expression of myxovirus resistance protein 1 in human mesangial cells: possible activation of innate immunity in the pathogenesis of lupus nephritis.

    PubMed

    Watanabe, Shojiro; Imaizumi, Tadaatsu; Tsuruga, Kazushi; Aizawa, Tomomi; Ito, Tatsuya; Matsumiya, Tomoh; Yoshida, Hidemi; Joh, Kensuke; Ito, Etsuro; Tanaka, Hiroshi

    2013-12-01

    Since viral infections activate type I interferon (IFN) pathways and cause subsequent release of IFN-dependent proinflammatory chemokines and cytokines, the innate immune system plays an important role in the pathogenesis of lupus nephritis (LN). It has been reported that human myxovirus resistance protein 1 (Mx1), a type I IFN-dependent transcript, acts against a wide range of RNA viruses. Although the expression of Mx1 in biopsy specimens obtained from patients with dermatomyositis and cutaneous lupus has been described, the expression of Mx1 in human mesangial cells (MCs) has remained largely unknown. We treated normal human MCs in culture with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expression of Mx1 by reverse transcription-polymerase chain reaction and western blotting. To elucidate the poly IC-signalling pathway, we subjected the cells to RNA interference against IFN-β. We also conducted an immunofluorescence study to examine mesangial Mx1 expression in biopsy specimens from patients with LN. Poly IC-induced Mx1 expression in MCs are shown both time- and dose-dependently, and RNA interference against IFN-β inhibited poly IC-induced Mx1 expression. Intense glomerular Mx1 expression was observed in biopsy specimens from patients with LN, whereas negative staining occurred in specimens from patients with IgA nephropathy or purpura nephritis. These preliminary observations support, at least in part, the theory of innate immune system activation in the pathogenesis of LN. PMID:24674141

  3. Lupus nephritis in Egyptian children: a 16-year experience.

    PubMed

    Elmougy, Atef; Sarhan, Amr; Hammad, Ayman; El-Refaey, Ahmed; Zedan, Mohammed; Eid, Riham; Laimon, Wafaa; Limon, Wafaa; Elrahman, Ashraf Abd; Elhussieni, Fatma; El-Sherbeny, Enas; Bakr, Ashraf

    2015-10-01

    We retrospectively evaluated the clinical features, histo-pathological patterns, treatment modalities, and outcome of children and adolescents with lupus nephritis (LN), followed-up in Lupus Clinic, Pediatric Nephrology Unit, Mansoura University Children's Hospital between January 1997 and December 2012. Out of 194 patients diagnosed with systemic lupus erythematosus (SLE), LN was reported in 136 (70 %) patient, they were 27 males (20 %) and 109 females (80 %). The mean age at presentation was 12.5 ± 2.9 years, the mean duration of follow up was 4.1 years (range 2 months-12 years). Hematuria was present in 79 patients (58 %), proteinuria in 126 (92.6 %), 38 of them were in nephrotic range, while renal impairment was documented in 20 patients (15 %). Renal biopsy was done in 132 patients; diagnosis of class II, III, IV, V were 23, 25, 39, and 2 % respectively. Second renal biopsy was indicated in 58 patients (insufficient first biopsy 2, follow up in 45, lupus flare in 8, no response to therapy in 3 patients), while the third one was needed in only eight patients. Steroids were the commonest initial medications; used in 128 patients (63 alone and 65 with others) and cyclophosphamide was used in 64 patients. At the last follow-up visit; 19 % of patients lost follow-up, 45 % had complete remission, 21 % still had active disease, 1 % had end-stage renal disease, and 11 % died. In conclusion, in Egypt, childhood SLE is associated with frequent and severe nephritis at presentation, and this may be attributed to genetic, ethnic, or environmental factors. PMID:25491938

  4. Lupus Nephritis: Animal Modeling of a Complex Disease Syndrome Pathology

    PubMed Central

    McGaha, Tracy L; Madaio, Michael P.

    2014-01-01

    Nephritis as a result of autoimmunity is a common morbidity associated with Systemic Lupus Erythematosus (SLE). There is substantial clinical and industry interest in medicinal intervention in the SLE nephritic process; however, clinical trials to specifically treat lupus nephritis have not resulted in complete and sustained remission in all patients. Multiple mouse models have been used to investigate the pathologic interactions between autoimmune reactivity and SLE pathology. While several models bear a remarkable similarity to SLE-driven nephritis, there are limitations for each that can make the task of choosing the appropriate model for a particular aspect of SLE pathology challenging. This is not surprising given the variable and diverse nature of human disease. In many respects, features among murine strains mimic some (but never all) of the autoimmune and pathologic features of lupus patients. Although the diversity often limits universal conclusions relevant to pathogenesis, they provide insights into the complex process that result in phenotypic manifestations of nephritis. Thus nephritis represents a microcosm of systemic disease, with variable lesions and clinical features. In this review, we discuss some of the most commonly used models of lupus nephritis (LN) and immune-mediated glomerular damage examining their relative strengths and weaknesses, which may provide insight in the human condition. PMID:25722732

  5. A pathophysiology-based approach to the diagnosis and treatment of lupus nephritis.

    PubMed

    Anders, Hans-Joachim; Rovin, Brad

    2016-09-01

    Lupus is no longer an unknown chameleon of medicine. Significant progress has been made on unraveling the pathogenesis of lupus and lupus nephritis, and how to treat the disease. Here we provide an update on the pathophysiology of lupus and its related kidney disease, consider areas of controversy in disease management, and discuss the unmet needs of lupus nephritis and how to address these needs. We focus on rethinking how innovative therapies for lupus nephritis should be evaluated and evolving strategies to more efficiently mitigate irreversible nephron loss in patients with lupus nephritis. PMID:27378475

  6. Why do patients with lupus nephritis die?

    PubMed Central

    Correia, P; Cameron, J S; Lian, J D; Hicks, J; Ogg, C S; Williams, D G; Chantler, C; Haycock, D G

    1985-01-01

    Over 20 years 42 of 138 patients with systemic lupus erythematosus "died"--that is, suffered actual death or went into terminal renal failure, or both; data from 41 were available for analysis. In most patients the causes of death were multiple. Twenty seven patients went into terminal renal failure, of whom 25 were offered dialysis treatment. Three regained renal function later, 12 survived on dialysis or with functioning kidney allografts--almost all with inactive lupus--but 13 died after starting dialysis, most within a few weeks or months. The principal causes were active lupus or infection. In those patients with renal failure after rapid deterioration in renal function (n = 14) there were nine deaths, while of 10 patients with a slow evolution into renal failure, only four died. Four patients with impaired and 10 with normal renal function died, again most often from complications of lupus or from infection. Vascular disease was a major cause of death in seven patients, all but two of whom were young; of 15 postmortem examinations, eight showed severe coronary artery atheroma, and three surviving patients required coronary bypass operations. Analysis of the timing of death or entry into renal failure showed that in 12 out of 13 patients who died within two years of onset the lupus was judged to be active, while this was true in only eight out of 19 patients who died later. Six of the seven vascular deaths occurred later than two years from onset, while only nine of 26 renal "deaths" occurred before two years; deaths from infections (n = 13) were distributed equally. Despite this and aggressive treatment of active disease, the principal cause of actual death was uncontrolled lupus. PMID:3917713

  7. Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus nephritis in mice.

    PubMed

    Grossman, Tamar R; Hettrick, Lisa A; Johnson, Robert B; Hung, Gene; Peralta, Raechel; Watt, Andrew; Henry, Scott P; Adamson, Peter; Monia, Brett P; McCaleb, Michael L

    2016-06-01

    Systemic lupus erythematosus is an autoimmune disease that manifests in widespread complement activation and deposition of complement fragments in the kidney. The complement pathway is believed to play a significant role in the pathogenesis and in the development of lupus nephritis. Complement factor B is an important activator of the alternative complement pathway and increasing evidence supports reducing factor B as a potential novel therapy to lupus nephritis. Here we investigated whether pharmacological reduction of factor B expression using antisense oligonucleotides could be an effective approach for the treatment of lupus nephritis. We identified potent and well tolerated factor B antisense oligonucleotides that resulted in significant reductions in hepatic and plasma factor B levels when administered to normal mice. To test the effects of factor B antisense oligonucleotides on lupus nephritis, we used two different mouse models, NZB/W F1 and MRL/lpr mice, that exhibit lupus nephritis like renal pathology. Antisense oligonucleotides mediated reductions in circulating factor B levels were associated with significant improvements in renal pathology, reduced glomerular C3 deposition and proteinuria, and improved survival. These data support the strategy of using factor B antisense oligonucleotides for treatment of lupus nephritis in humans. PMID:26307001

  8. Podocyte-associated mRNA profiles in kidney tissue and in urine of patients with active lupus nephritis

    PubMed Central

    dos Santos, Mariane; Bringhenti, Rafael N; Rodrigues, Patrícia G; do Nascimento, Jonathan F; Pereira, Sane V; Zancan, Rafael; Monticielo, Odirlei A; Gasparin, Andrese A; de Castro, Waldir P; Veronese, Francisco V

    2015-01-01

    Aim: Glomerular deposition of immune complexes and inflammation induce podocyte injury in lupus nephritis (LN). This study hypothesized that the severity of the histological lesions of LN affects podocyte-associated mRNAs profiles in kidney tissue and in urine. Methods: Thirty-three patients with LN were grouped according to the presence of mild mesangial (classes I and II) or moderate-to-severe immune complex deposition, proliferation and/or inflammation (classes III, IV and V) in kidney biopsy. Tissue and urine mRNA of nephrin, podocin, podocalyxin, α-actinin-4, transient receptor potential cation channel 6, and of growth factors VEGF-A and TGF-β1 and the transcription factor FOXP3 were measured using real time polymerase chain reaction. These mRNAs were correlated with histological severity of LN, extent of glomerular immune deposits, and tissue infiltrating cells. Results: Podocyte-associated mRNAs were inhibited in renal tissue of patients with LN irrespective of histological class when compared to controls. However, significantly higher expression of podocyte mRNAs in urine, including those of growth factors and FOXP3, were found in patients with moderate-to-severe nephritis, mostly in class III and IV proliferative forms. The number of invading CD8+ T cells, B cells and macrophages correlated positively with urine podocyte-associated mRNAs. Urine podocyte mRNAs also correlated with proteinuria. Conclusions: Inhibition of podocyte-associated mRNAs in kidney tissue suggests that podocyte injury occurs regardless of class severity of LN. Increased urinary excretion of podocyte mRNAs, mostly in patients with moderate-to-severe lesions, may reflect a greater burden of glomerular damage with detachment of podocytes into the urine. PMID:26191151

  9. MicroRNAs Implicated in the Immunopathogenesis of Lupus Nephritis

    PubMed Central

    Chafin, Cristen B.; Reilly, Christopher M.

    2013-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the deposition of immune complexes due to widespread loss of immune tolerance to nuclear self-antigens. Deposition in the renal glomeruli results in the development of lupus nephritis (LN), the leading cause of morbidity and mortality in SLE. In addition to the well-recognized genetic susceptibility to SLE, disease pathogenesis is influenced by epigenetic regulators such as microRNAs (miRNAs). miRNAs are small, noncoding RNAs that bind to the 3′ untranslated region of target mRNAs resulting in posttranscriptional gene modulation. miRNAs play an important and dynamic role in the activation of innate immune cells and are critical in regulating the adaptive immune response. Immune stimulation and the resulting cytokine milieu alter miRNA expression while miRNAs themselves modify cellular responses to stimulation. Here we examine dysregulated miRNAs implicated in LN pathogenesis from human SLE patients and murine lupus models. The effects of LN-associated miRNAs in the kidney, peripheral blood mononuclear cells, macrophages, mesangial cells, dendritic cells, and splenocytes are discussed. As the role of miRNAs in immunopathogenesis becomes delineated, it is likely that specific miRNAs may serve as targets for therapeutic intervention in the treatment of LN and other pathologies. PMID:23983769

  10. 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

  11. 77 FR 38305 - Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus-Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... a notice published in the Federal Register of June 22, 2010 (75 FR 35492), FDA announced the... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Withdrawal of Guidance AGENCY: Food...

  12. A77 1726, the active metabolite of leflunomide, attenuates lupus nephritis by promoting the development of regulatory T cells and inhibiting IL-17-producing double negative T cells.

    PubMed

    Qiao, Guilin; Yang, Lifen; Li, Zhenping; Williams, James W; Zhang, Jian

    2015-04-01

    Lupus nephritis (LN) is a challenging problem that affects 50% of patients with systemic lupus erythematosus (SLE) without effective therapy. Here, we report that A77 1726, the active metabolite of leflunomide, effectively inhibits development of LN and attenuates the generalized autoimmune features. A77 1726 suppresses the expansion of double negative (DN) T cells, and inhibits T and B cell activation. Intriguingly, A77 1726 treatment significantly increases CD4(+)Foxp3(+) regulatory T cells but suppresses potential "pathogenic" IL-17-producing DN T cells in lymph nodes. In vitro experiment shows that A77 1726 potentiates the conversion of naive CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) inducible regulatory T cells (iTregs) by inhibiting Akt. Taken together, our data indicate that the therapeutic effects of A77 1726 in murine LN are mediated, at least in part, by augmenting iTregs which suppress pathogenic IL-17-producing DN T cells through an Akt-dependent mechanism. PMID:25638413

  13. Outcome of the acute glomerular injury in proliferative lupus nephritis

    SciTech Connect

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. )

    1989-09-01

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

  14. P2X7 Blockade Attenuates Murine Lupus Nephritis by Inhibiting Activation of the NLRP3/ASC/Caspase 1 Pathway

    PubMed Central

    Zhao, Jijun; Wang, Hongyue; Dai, Chao; Wang, Hongyang; Zhang, Hui; Huang, Yuefang; Wang, Shuang; Gaskin, Felicia; Yang, Niansheng; Fu, Shu Man

    2014-01-01

    Objective The NLRP3 inflammasome plays key roles in inflammation and autoimmunity, and puriner-gic receptor P2X7 has been proposed to be upstream of NLRP3 activation. The aim of the present study, using murine models, was to investigate whether the P2X7/ NLRP3 inflammasome pathway contributes to the pathogenesis of lupus nephritis (LN). Methods MRL/lpr mice were treated with the selective P2X7 antagonist brilliant blue G (BBG) for 8 weeks. Following treatment, the severity of renal lesions, production of anti-double-stranded DNA (anti-dsDNA) antibodies, rate of survival, activation of the NLRP3/ ASC/caspase 1 inflammasome pathway, and ratio of Thl7 cells to Treg cells were evaluated. P2X7-targeted small interfering RNA (siRNA) was also used for in vivo intervention. Similar evaluations were carried out in NZM2328 mice, a model of LN in which the disease was accelerated by administration of adenovirus-expressing interferon-α (AdIFNα). Results Significant up-regulation of P2X7/NLRP3 inflammasome signaling molecules was detected in the kidneys of MLR/lpr mice as compared with normal control mice. Blockade of P2X7 activation by BBG suppressed NLRP3/ASC/caspase 1 assembly and the subsequent release of interleukin-1β (IL-1β), resulting in a significant reduction in the severity of nephritis and circulating anti-dsDNA antibodies. The lifespan of the treated mice was significantly prolonged. BBG treatment reduced the serum levels of IL-1β and IL-17 and the Thl7:Treg cell ratio. Similar results were obtained by specific siRNA silencing of P2X7 in vivo. The effectiveness of BBG treatment in modulating LN was confirmed in NZM2328 mice with AdIFNα-accelerated disease. Conclusion Activation of the P2X7 signaling pathway accelerates murine LN by activating the NLRP3/ASC/caspase 1 inflammasome, resulting in increased IL-1β production and enhanced Thl7 cell polarization. Thus, targeting of the P2X7/NLRP3 pathway should be considered as a novel therapeutic strategy in

  15. Lupus nephritis: clinicopathological study of 162 cases in Thailand.

    PubMed Central

    Parichatikanond, P; Francis, N D; Malasit, P; Laohapand, T; Nimmannit, S; Singchoovong, L; Nilwarangkur, S; Chrirawong, P; Vanichakarn, S

    1986-01-01

    One hundred and sixty two cases of lupus nephritis biopsied over three years in Thailand were studied. A pattern of clinical and histological renal disease very similar to that seen in the United States or Europe emerged. The predominant histological type was World Health Organisation class IV (diffuse proliferative; 58.6%). Patients with renal insufficiency (creatinine greater than or equal to 2 mg/100 ml) or hypertension at the time of biopsy had a considerably worse three year survival. Certain features such as sclerotic glomeruli, tubular atrophy, and an interstitial mononuclear cell infiltrate were significantly associated with a worse outcome (0.05 greater than p greater than 0.01), and patients who died with poor renal function had significantly higher chronicity scores than those in other groups (p less than 0.05). These findings emphasise the importance of chronic renal damage in the morbidity and mortality of patients with lupus nephritis. PMID:3485117

  16. Chemokines and Chemokine Receptors in the Development of Lupus Nephritis

    PubMed Central

    2016-01-01

    Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN. PMID:27403037

  17. Chemokines and Chemokine Receptors in the Development of Lupus Nephritis.

    PubMed

    Liao, Xiaofeng; Pirapakaran, Tharshikha; Luo, Xin M

    2016-01-01

    Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN. PMID:27403037

  18. Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic lupus erythematosus

    PubMed Central

    Thurman, Joshua M.; Serkova, Natalie J.

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple different organs, including the kidneys and central nervous system (CNS). Conventional radiological examinations in SLE patients include volumetric/ anatomical computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US). The utility of these modalities is limited, however, due to the complexity of the disease. Furthermore, standard CT and MRI contrast agents are contraindicated in patients with renal impairment. Various radiologic methods are currently being developed to improve disease characterization in patients with SLE beyond simple anatomical endpoints. Physiological non-contrast MRI protocols have been developed to assess tissue oxygenation, glomerular filtration, renal perfusion, interstitial diffusion, and inflammation-driven fibrosis in lupus nephritis (LN) patients. For neurological symptoms, vessel size imaging (VSI, an MRI approach utilizing T2-relaxing iron oxide nanoparticles) has shown promise as a diagnostic tool. Molecular imaging probes (mostly for MRI and nuclear medicine imaging) have also been developed for diagnosing SLE with high sensitivity, and for monitoring disease activity. This paper reviews the challenges in evaluating disease activity in patients with LN and neuropsychiatric systemic lupus erythematosus (NPSLE). We describe novel MRI and positron-emission tomography (PET) molecular imaging protocols using targeted iron oxide nanoparticles and radioactive ligands, respectively, for detection of SLE-associated inflammation. PMID:26309728

  19. Treatment of lupus nephritis with total lymphoid irradiation. Observations during a 12-79-month followup

    SciTech Connect

    Strober, S.; Farinas, M.C.; Field, E.H.; Solovera, J.J.; Kiberd, B.A.; Myers, B.D.; Hoppe, R.T.

    1988-07-01

    Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.

  20. Reducing progression of experimental lupus nephritis via inhibition of the B7/CD28 signaling pathway.

    PubMed

    Huang, Li; Kong, Yong; Wang, Jing; Sun, Jie; Shi, Qin; Qiu, Yu-Hua

    2015-09-01

    The aim of the present study was to evaluate the effects of the B7/cluster of differentiation (CD)28 signaling pathway on experimental lupus nephritis and examine the molecular mechanism involved by inhibiting the B7/CD28 signaling pathway. A lupus nephritis model in C57BL/6 J mice was induced via intraperitoneal injection of pristane. A recombinant B7‑1 short hairpin RNA (shRNA) lentivirus vector was constructed by synthesis and splicing. A neutralizing mouse anti‑human B7‑1 antibody termed 4E5 was also prepared. The mouse model of lupus nephritis was treated with B7‑1 shRNA and 4E5 via injection through the tail vein. The silencing effects of B7‑1 shRNA lentiviral infection on target molecules were evaluated using immunofluorescence and flow cytometry. The levels of protein in the urine were detected using Albustix test paper each month over 10 months. The concentration of interleukin (IL)‑4 and interferon‑γ in the serum was determined using an ELISA. The immune complex (IC) deposits in the kidney were analyzed using direct immunofluorescence. The results demonstrated that the C57BL/6 J mouse lupus nephritis model was successfully constructed with immune cells activated in the spleen of the mice, increases in the concentration of anti‑nuclear antibody (ANA) and anti‑double stranded DNA antibodies as well as positive IC formation. Following B7‑1 shRNA lentivirus or 4E5 treatment, CD11b+B7‑1+, CD11c+B7‑1+ and CD21+B7‑1+ cells in the spleen of the mice were significantly reduced. The concentration of ANA and IL‑4 in the serum was also decreased. The concentration of urine protein was reduced and it was at its lowest level in the 4E5 early intervention group. It was also revealed that the immunofluorescence intensity of the IC deposits was weak in the 4E5 early intervention group. In conclusion, inhibiting the B7‑1/CD28 signaling pathway is able to alleviate experimental lupus nephritis and provides an experimental basis for the

  1. Reducing progression of experimental lupus nephritis via inhibition of the B7/CD28 signaling pathway

    PubMed Central

    HUANG, LI; KONG, YONG; WANG, JING; SUN, JIE; SHI, QIN; QIU, YU-HUA

    2015-01-01

    The aim of the present study was to evaluate the effects of the B7/cluster of differentiation (CD)28 signaling pathway on experimental lupus nephritis and examine the molecular mechanism involved by inhibiting the B7/CD28 signaling pathway. A lupus nephritis model in C57BL/6 J mice was induced via intraperitoneal injection of pristane. A recombinant B7-1 short hairpin RNA (shRNA) lentivirus vector was constructed by synthesis and splicing. A neutralizing mouse anti-human B7-1 antibody termed 4E5 was also prepared. The mouse model of lupus nephritis was treated with B7-1 shRNA and 4E5 via injection through the tail vein. The silencing effects of B7-1 shRNA lentiviral infection on target molecules were evaluated using immunofluorescence and flow cytometry. The levels of protein in the urine were detected using Albustix test paper each month over 10 months. The concentration of interleukin (IL)-4 and interferon-γ in the serum was determined using an ELISA. The immune complex (IC) deposits in the kidney were analyzed using direct immunofluorescence. The results demonstrated that the C57BL/6 J mouse lupus nephritis model was successfully constructed with immune cells activated in the spleen of the mice, increases in the concentration of anti-nuclear antibody (ANA) and anti-double stranded DNA antibodies as well as positive IC formation. Following B7-1 shRNA lentivirus or 4E5 treatment, CD11b+B7-1+, CD11c+B7-1+ and CD21+B7-1+ cells in the spleen of the mice were significantly reduced. The concentration of ANA and IL-4 in the serum was also decreased. The concentration of urine protein was reduced and it was at its lowest level in the 4E5 early intervention group. It was also revealed that the immunofluorescence intensity of the IC deposits was weak in the 4E5 early intervention group. In conclusion, inhibiting the B7-1/CD28 signaling pathway is able to alleviate experimental lupus nephritis and provides an experimental basis for the therapeutic use of blocking the B7

  2. Unmet medical needs in lupus nephritis: solutions through evidence-based, personalized medicine

    PubMed Central

    Anders, Hans-Joachim; Weidenbusch, Marc; Rovin, Brad

    2015-01-01

    Lupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy. This review discusses the underlying reasons for these unmet medical needs and options of how to overcome them in the future. PMID:26413272

  3. Unmet medical needs in lupus nephritis: solutions through evidence-based, personalized medicine.

    PubMed

    Anders, Hans-Joachim; Weidenbusch, Marc; Rovin, Brad

    2015-10-01

    Lupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy. This review discusses the underlying reasons for these unmet medical needs and options of how to overcome them in the future. PMID:26413272

  4. Remission and withdrawal of therapy in lupus nephritis.

    PubMed

    Moroni, Gabriella; Raffiotta, Francesca; Ponticelli, Claudio

    2016-08-01

    There is agreement that early diagnosis and aggressive treatment of lupus nephritis exacerbations are of paramount importance to achieve remission and prevent the development of irreversible lesions. There is less agreement about the optimal duration of maintenance treatment. Instead, the prolonged exposure to corticosteroids and/or immunosuppressive drugs can cause invalidating or even life-threatening complications. It is still unclear if these drugs can be safely withdrawn in lupus patients. We were able to completely withdraw therapy in around 1/3 of our patients after a follow-up of 5 years or more; 60 % of them never had to start therapy again. Based on our own experience, discontinuation of therapy should be applied only in selected cases, i.e. patients who received maintenance therapy for at least 5 years and are in complete renal remission for at least 3 years. Antimalarial agents are helpful in maintaining the remission after withdrawal of therapy. However, to achieve these goals, drugs should be tapered off very slowly and under strict surveillance. If all these prerequisites are satisfied, the withdrawal of therapy in patients with lupus nephritis may be considered safe, may improve the patients' quality of life and may reduce the damage accrual. PMID:27146861

  5. Calcineurin inhibitors may be a reasonable alternative to cyclophosphamide in the induction treatment of active lupus nephritis: A systematic review and meta-analysis

    PubMed Central

    YANG, MIN; LI, MIN; HE, WEI; WANG, BIN; GU, YONG

    2014-01-01

    Although the accepted standard of care during the induction treatment of active lupus nephritis (LN) has been cyclophosphamide (CYC), recent trials suggest that calcineurin inhibitors (CNIs), which include cyclosporine A (CsA) and tacrolimus (TAC), may be just as, or even more, effective and less toxic than CYC. A systematic review and meta-analysis were performed to evaluate the clinical effects of CNIs on active LN compared with those of CYC. In the present study, clinical trials that compared CNIs with CYC in the induction therapy of active LN were searched in the Cochrane Library, Ovid and PubMed databases. The clinical data on renal remission and side-effects were collected and analyzed. The relative risk (RR) and 95% confidence intervals (CIs) were calculated. As a result, six controlled trials involving 265 patients were included in the meta-analysis, four of which compared TAC (treatment group) with CYC (control group), and the other two compared CsA (treatment group) with CYC (control group). CNIs were superior to CYC for higher complete remission (RR=1.56, 95% CI 1.14–2.15, Z=2.74, P=0.006) and better overall response/total remission (RR=1.23, 95% CI 1.07–1.42, Z=2.87, P=0.004) and had fewer side-effects. Among the CNIs, TAC demonstrated more favorable results than CsA. Therefore, it was concluded that CNIs may be a reasonable alternative to CYC in the induction treatment of active LN. However, large-scale, multicenter, well-designed clinical trials should be adopted to further confirm this conclusion. PMID:24926363

  6. Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy

    PubMed Central

    Li, Qiu-Yu; Yu, Feng; Zhou, Fu-De; Zhao, Ming-Hui

    2016-01-01

    Abstract The aim of this study was to evaluate the efficacy of plasmapheresis in patients with lupus nephritis-combined thrombotic microangiopathy (TMA) in a Chinese cohort. Clinical and therapeutic data of patients with lupus nephritis–combined TMA were collected retrospectively. A comparison between those with and without plasmapheresis was performed. Seventy patients with renal biopsy-proven TMA in lupus nephritis were treated with conventional combined corticosteroid and immunosuppressive agents as induction therapy, 9 of the 70 patients received additional plasmapheresis. The plasmapheresis group presented with more severe SLE and renal activity indices, including a significant higher ratio of neurologic disorder (P = 0.025), lower level of platelet count (P = 0.009), higher value of serum creatinine (P = 0.038), higher percentage of anti-cardiolipin antibodies positive (P = 0.001), and higher Systemic Lupus Erythematosus Disease Activity Index scores (P = 0.012), than that of the nonplasmapheresis group. However, the plasmapheresis group had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.03). As the baseline data were significantly different between the 2 groups, the propensity score match was further designed to avoid retrospective bias. After re-analysis, the plasmapheresis group still had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.018). More importantly, the plasmapheresis group had significant less composite endpoints than that of the nonplasmapheresis group (P = 0.005). Our study suggested that additional plasmapheresis on conventional induction therapy may benefit patients with lupus nephritis-combined TMA, which warrants further explorations. PMID:27149490

  7. Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis: A Large Multicenter Cross-Sectional Study.

    PubMed

    Pang, Yun; Tan, Ying; Li, Yongzhe; Zhang, Jianchun; Guo, Yongbing; Guo, Zhiling; Zhang, Chengying; Yu, Feng; Zhao, Ming-Hui

    2016-01-01

    Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0

  8. Treatment of intractable lupus nephritis with total lymphoid irradiation

    SciTech Connect

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-04-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

  9. Clearing the complexity: immune complexes and their treatment in lupus nephritis

    PubMed Central

    Toong, Catherine; Adelstein, Stephen; Phan, Tri Giang

    2011-01-01

    Systemic lupus erythematosus (SLE) is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies) and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control. PMID:21694945

  10. Resistin as a potential marker of renal disease in lupus nephritis.

    PubMed

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-03-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  11. Resistin as a potential marker of renal disease in lupus nephritis

    PubMed Central

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-01-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  12. Association of STAT4 Polymorphism with Severe Renal Insufficiency in Lupus Nephritis

    PubMed Central

    Bolin, Karin; Sandling, Johanna K.; Zickert, Agneta; Jönsen, Andreas; Sjöwall, Christopher; Svenungsson, Elisabet; Bengtsson, Anders A.; Eloranta, Maija-Leena; Rönnblom, Lars; Syvänen, Ann-Christine; Gunnarsson, Iva; Nordmark, Gunnel

    2013-01-01

    Lupus nephritis is a cause of significant morbidity in systemic lupus erythematosus (SLE) and its genetic background has not been completely clarified. The aim of this investigation was to analyze single nucleotide polymorphisms (SNPs) for association with lupus nephritis, its severe form proliferative nephritis and renal outcome, in two Swedish cohorts. Cohort I (n = 567 SLE cases, n =  512 controls) was previously genotyped for 5676 SNPs and cohort II (n = 145 SLE cases, n = 619 controls) was genotyped for SNPs in STAT4, IRF5, TNIP1 and BLK. Case-control and case-only association analyses for patients with lupus nephritis, proliferative nephritis and severe renal insufficiency were performed. In the case-control analysis of cohort I, four highly linked SNPs in STAT4 were associated with lupus nephritis with genome wide significance with p = 3.7×10−9, OR 2.20 for the best SNP rs11889341. Strong signals of association between IRF5 and an HLA-DR3 SNP marker were also detected in the lupus nephritis case versus healthy control analysis (p <0.0001). An additional six genes showed an association with lupus nephritis with p <0.001 (PMS2, TNIP1, CARD11, ITGAM, BLK and IRAK1). In the case-only meta-analysis of the two cohorts, the STAT4 SNP rs7582694 was associated with severe renal insufficiency with p  = 1.6×10−3 and OR 2.22. We conclude that genetic variations in STAT4 predispose to lupus nephritis and a worse outcome with severe renal insufficiency. PMID:24386384

  13. Insights into the epidemiology and management of lupus nephritis from the US rheumatologist's perspective.

    PubMed

    Hoover, Paul J; Costenbader, Karen H

    2016-09-01

    Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus that disproportionately affects nonwhites and those in lower socioeconomic groups. This review discusses recent data on the incidence, prevalence, and outcomes of patients with lupus nephritis with a focus on low-income US Medicaid patients. We also review recent guidelines on diagnosis, treatment, and screening for new onset and relapses of lupus nephritis. Finally, we discuss the management of lupus nephritis from a rheumatologist's perspective, including vigilance for the common adverse events related to disease and treatment, and we review prevention and new treatment strategies. PMID:27344205

  14. Genetic contributions of nonautoimmune SWR mice toward lupus nephritis.

    PubMed

    Xie, S; Chang, S; Yang, P; Jacob, C; Kaliyaperumal, A; Datta, S K; Mohan, C

    2001-12-15

    (SWR x New Zealand Black (NZB))F(1) (or SNF(1)) mice succumb to lupus nephritis. Although several NZB lupus susceptibility loci have been identified in other crosses, the potential genetic contributions of SWR to lupus remain unknown. To ascertain this, a panel of 86 NZB x F(1) backcross mice was immunophenotyped and genome scanned. Linkage analysis revealed four dominant SWR susceptibility loci (H2, Swrl-1, Swrl-2, and Swrl-3) and a recessive NZB locus, Nba1. Early mortality was most strongly linked to the H2 locus on chromosome (Chr) 17 (log likelihood of the odds (LOD) = 4.59 - 5.38). Susceptibility to glomerulonephritis was linked to H2 (Chr 17, LOD = 2.37 - 2.70), Swrl-2 (Chr 14, 36 cM, LOD = 2.48 - 2.71), and Nba1 (Chr 4, 75 cM, LOD = 2.15 - 2.23). IgG antinuclear autoantibody development was linked to H2 (Chr 17, LOD = 4.92 - 5.48), Swrl-1 (Chr 1, 86 cM, colocalizing with Sle1 and Nba2, LOD = 2.89 - 2.91), and Swrl-3 (Chr 18, 14 cM, LOD = 2.07 - 2.13). For each phenotype, epistatic interaction of two to three susceptibility loci was required to attain the high penetrance levels seen in the SNF(1) strain. Although the SWR contributions H2, Swrl-1, and Swrl-2 map to loci previously mapped in other strains, often linked to very similar phenotypes, Swrl-3 appears to be a novel locus. In conclusion, lupus in the SNF(1) strain is truly polygenic, with at least four dominant contributions from the SWR strain. The immunological functions and molecular identities of these loci await elucidation. PMID:11739537

  15. Renal flare prediction and prognosis in lupus nephritis Hispanic patients.

    PubMed

    Mejía-Vilet, J M; Córdova-Sánchez, B M; Arreola-Guerra, J M; Morales-Buenrostro, L E; Uribe-Uribe, N O; Correa-Rotter, R

    2016-03-01

    We performed a retrospective cohort analysis focusing on lupus nephritis renal flare incidence and outcome predictors. One hundred and eighteen patients with biopsy-proven lupus nephritis were segregated by induction/maintenance regimes. The primary outcome was the proportion of patients experiencing renal flare. Secondary assessment included doubling of serum creatinine and development of end-stage renal disease. After a median follow-up of 31 months (interquartile range 21-46) from the date of response to induction therapy, 47 patients (39.8%) developed a renal flare. Azathioprine-maintained patients had a higher risk of renal flare compared with mycophenolate mofetil-maintained patients (hazard ratio 2.53, 95% confidence interval 1.39-4.59, p < 0.01). Age (hazard ratio 0.96, 0.92-0.99, p = 0.03), serum creatinine at presentation (hazard ratio 1.76, 1.13-2.76, p = 0.01), complete remission after induction therapy (hazard ratio 0.28, 0.14-0.56, p < 0.001) and azathioprine maintenance therapy (hazard ratio 4.78, 2.16-10.6, p < 0.001) were associated with renal flare on multivariate analysis. Ten patients progressed to end-stage renal disease (8.5%) by a median 32.5 months. Age (hazard ratio 0.88, 0.77-0.99, p = 0.05), complete remission after induction therapy (hazard ratio 0.08, 0.01-0.94, p = 0.04) and severe nephritic flare (hazard ratio 13.6, 1.72-107.7, p = 0.01) were associated with end-stage renal disease development. Azathioprine maintenance therapy is associated with a higher incidence of relapse in the Mexican-mestizo population. Younger age and nephritic flares predict development of end-stage renal disease. PMID:26405028

  16. Insulin-Like Growth Factor Binding Protein-4 as a Marker of Chronic Lupus Nephritis

    PubMed Central

    Han, Jie; Ye, Yujin; Singh, Sandeep; Zhou, Jinchun; Li, Yajuan; Ding, Huihua; Li, Quan-zhen; Zhou, Xin; Putterman, Chaim; Saxena, Ramesh; Mohan, Chandra

    2016-01-01

    Kidney biopsy remains the mainstay of Lupus Nephritis (LN) diagnosis and prognostication. The objective of this study is to identify non-invasive biomarkers that closely parallel renal pathology in LN. Previous reports have demonstrated that serum Insulin-like growth factor binding protein 4 (IGFBP-4) was increased in diabetic nephropathy in both animal models and patients. We proceeded to assess if IGFBP4 could be associated with LN. We performed ELISA using the serum of 86 patients with LN. Normal healthy adults (N = 23) and patients with other glomerular diseases (N = 20) served as controls. Compared to the healthy controls or other glomerular disease controls, serum IGFBP-4 levels were significantly higher in the patients with LN. Serum IGFBP-4 did not correlate well with systemic lupus erythematosus disease activity index (SLEDAI), renal SLEDAI or proteinuria, but it did correlate with estimated glomerular filtration rate (R = 0.609, P < 0.0001). Interestingly, in 18 patients with proliferative LN whose blood samples were obtained at the time of renal biopsy, serum IGFBP-4 levels correlated strongly with the chronicity index of renal pathology (R = 0.713, P < 0.001). IGFBP-4 emerges a potential marker of lupus nephritis, reflective of renal pathology chronicity changes. PMID:27019456

  17. Intracranial hypertension: A rare presentation of lupus nephritis

    PubMed Central

    Yadav, Praveen; Nair, Anishkumar; Cherian, Ajith; Sibi, N. S.; Kumar, Ashwini

    2010-01-01

    A 14-year-old male presented with bilateral papilledema, growth retardation and absent secondary sexual characters. He had a past history of fever, headache and fatigue of 6 months duration. The diagnosis of intracranial hypertension (IH) was confirmed by an increased intracranial pressure and normal neuroimaging studies of the brain, except for partial empty sella, prominent perioptic cerebrospinal fluid (CSF) spaces and buckling of optic nerves. Evaluation showed erythrocyte sedimentation rate (ESR) of 150 mm/hr, positive antinuclear antibody (ANA), anti dsDNA and anti ribosomal P protein. Renal biopsy revealed diffuse segmental proliferative lupus nephritis (LN) class IV S (A) confirming the diagnosis of systemic lupus erythematosus (SLE). Treatment of LN with intravenous pulse methyl prednisolone and cyclophosphamide was effective in normalizing the CSF pressure, resulting in express and dramatic resolution of symptomatology. In a case of IH, SLE must be considered. IH, growth retardation and absence of sexual characters may be presenting manifestations of a chronic systemic inflammatory disease like SLE. These manifestations may act as a pointer to associated advanced grades of LN, which can be totally asymptomatic and missed without a renal biopsy. PMID:21559160

  18. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

    PubMed

    Zavada, J; Pesickova, Ss; Rysava, R; Olejarova, M; Horák, P; Hrncír, Z; Rychlík, I; Havrda, M; Vítova, J; Lukác, J; Rovensky, J; Tegzova, D; Böhmova, J; Zadrazil, J; Hána, J; Dostál, C; Tesar, V

    2010-10-01

    Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300) PMID:20605876

  19. Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis

    PubMed Central

    Frieri, Marianne; Heuser, William; Bliss, Joshua

    2015-01-01

    Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis. Lupus nephritis is a major complication of systemic lupus erythematosus (SLE) that can lead to significant illness or even death without proper intervention and treatment. With vast implications through a novel mechanism, belimumab offers a new standard of treatment for physicians in the complications associated with SLE, specifically lupus nephritis. By targeting B cell signaling and maturation, belimumab is able to mitigate the underlying pathological complications surrounding SLE. Phase 3 clinical trials with belimumab have depicted clinically efficacious applications, suggesting belimumab as a revolutionary breakthrough in the treatment armamentarium for practicing clinicians. This article explains the precise mechanism of action of belimumab on the soluble protein BlyS that plays a major role in the pathogenesis of lupus nephritis. In addition, the extensive pharmacokinetics and clinical implications are exemplified in this review with belimumab's comparison with standard therapeutic guidelines for the treatment of lupus nephritis. PMID:25969652

  20. Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor.

    PubMed Central

    Rajagopalan, S; Zordan, T; Tsokos, G C; Datta, S K

    1990-01-01

    The antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. In spite of this obstacle, we show that T helper (Th) cell lines that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (approximately 15%) of these lines had the ability to selectively augment the production of pathogenic anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the alpha beta T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the alpha beta TCR and 7 expressing the gamma delta TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients' B cells were involved in stimulating an autoreactive proliferation of the gamma delta Th cells. These studies demonstrate a novel helper activity of certain gamma delta T cells in a spontaneous autoimmune response. Images PMID:2144899

  1. Long-term outcomes of end-stage kidney disease for patients with lupus nephritis.

    PubMed

    Zhang, Lei; Lee, Gavin; Liu, Xusheng; Pascoe, Elaine M; Badve, Sunil V; Boudville, Neil C; Clayton, Philip A; Hawley, Carmel M; Kanellis, John; McDonald, Stephen P; Peh, Chen Au; Polkinghorne, Kevan R; Johnson, David W

    2016-06-01

    Patient outcomes in end-stage kidney disease (ESKD) secondary to lupus nephritis have not been well described. To help define this we compared dialysis and transplant outcomes of patients with ESKD due to lupus nephritis to all other causes. All patients diagnosed with ESKD who commenced renal replacement therapy in Australia and New Zealand (1963-2012) were included. Clinical outcomes were evaluated in both a contemporary cohort (1998-2012) and the entire 50-year cohort. Of 64,160 included patients, 744 had lupus nephritis as the primary renal disease. For the contemporary cohort of 425 patients with lupus nephritis, the 5-year dialysis patient survival rate was 69%. Of 176 contemporary patients with lupus nephritis who received their first renal allograft, the 5-year patient, overall renal allograft, and death-censored renal allograft survival rates were 95%, 88%, and 93%, respectively. Patients with lupus nephritis had worse dialysis patient survival (adjusted hazard ratio 1.33, 95% confidence interval 1.12-1.58) and renal transplant patient survival (adjusted hazard ratio 1.87, 95% confidence interval 1.18-2.98), but comparable overall renal allograft survival (adjusted hazard ratio 1.19, 95% confidence interval 0.84-1.68) and death-censored renal allograft survival (adjusted hazard ratio 1.05, 95% confidence interval 0.68-1.62) compared with ESKD controls. Similar results were found in the entire cohort and when using competing-risks analysis. Thus, the ESKD of lupus nephritis was associated with worse dialysis and transplant patient survival but comparable renal allograft survival compared with other causes of ESKD. PMID:27165824

  2. LAPping up dead cells to prevent lupus nephritis: a novel role for noncanonical autophagy in autoimmunity.

    PubMed

    Leventhal, Jeremy S; Ross, Michael J

    2016-08-01

    The mechanisms underlying the development of systemic lupus erythematosus and lupus nephritis remain poorly understood. A recent study demonstrates that deficiencies in the immune system's ability to degrade scavenged dead cells via noncanonical autophagy is sufficient to break immune tolerance and produce features commonly seen in lupus, including circulating autoantibodies, inflammatory cytokines, and nephritis. This work provides a possible mechanism for the association of polymorphisms in autophagy genes with the risk of lupus. PMID:27418084

  3. Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

    PubMed Central

    2012-01-01

    Introduction Microthrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN. Methods Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data. Results Microthrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome. Conclusions Microthrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series. PMID:22640796

  4. Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy: A Case Series Study.

    PubMed

    Li, Qiu-Yu; Yu, Feng; Zhou, Fu-De; Zhao, Ming-Hui

    2016-05-01

    The aim of this study was to evaluate the efficacy of plasmapheresis in patients with lupus nephritis-combined thrombotic microangiopathy (TMA) in a Chinese cohort.Clinical and therapeutic data of patients with lupus nephritis-combined TMA were collected retrospectively. A comparison between those with and without plasmapheresis was performed.Seventy patients with renal biopsy-proven TMA in lupus nephritis were treated with conventional combined corticosteroid and immunosuppressive agents as induction therapy, 9 of the 70 patients received additional plasmapheresis. The plasmapheresis group presented with more severe SLE and renal activity indices, including a significant higher ratio of neurologic disorder (P = 0.025), lower level of platelet count (P = 0.009), higher value of serum creatinine (P = 0.038), higher percentage of anti-cardiolipin antibodies positive (P = 0.001), and higher Systemic Lupus Erythematosus Disease Activity Index scores (P = 0.012), than that of the nonplasmapheresis group. However, the plasmapheresis group had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.03). As the baseline data were significantly different between the 2 groups, the propensity score match was further designed to avoid retrospective bias. After re-analysis, the plasmapheresis group still had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.018). More importantly, the plasmapheresis group had significant less composite endpoints than that of the nonplasmapheresis group (P = 0.005).Our study suggested that additional plasmapheresis on conventional induction therapy may benefit patients with lupus nephritis-combined TMA, which warrants further explorations. PMID:27149490

  5. HMGB1: a smoking gun in lupus nephritis?

    PubMed Central

    2012-01-01

    High-mobility group box 1 protein (HMGB1) is a prototypic alarmin that is released from activated and dying cells. Because of its proinflammatory activities, HMGB1 could mediate key events in the pathogenesis of systemic lupus erythematosus, a possibility supported by elevations of HMGB1 in patient blood and increased expression in renal biopsies. The biology of HMGB1 is complicated, however, and its activity is dependent on redox state as well as binding to other molecules such as cytokines. Defining more precisely the role of HMGB1 in lupus will require treatment studies to block the activity of this alarmin in animal models and ultimately patients. PMID:22423653

  6. Identification of unique microRNA signature associated with lupus nephritis.

    PubMed

    Te, Jeannie L; Dozmorov, Igor M; Guthridge, Joel M; Nguyen, Kim L; Cavett, Joshua W; Kelly, Jennifer A; Bruner, Gail R; Harley, John B; Ojwang, Joshua O

    2010-01-01

    MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression. In this study we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in peripheral blood mononuclear cells (PBMCs) and Epstein-Barr Virus (EBV)-transformed cell lines obtained from lupus nephritis affected patients and unaffected controls. TaqMan-based stem-loop real-time polymerase chain reaction was used for validation. Microarray analysis of miRNA expressed in both African American (AA) and European American (EA) derived lupus nephritis samples revealed 29 and 50 differentially expressed miRNA, respectively, of 850 tested. There were 18 miRNA that were differentially expressed in both racial groups. When samples from both racial groups and different specimen types were considered, there were 5 primary miRNA that were differentially expressed. We have identified 5 miRNA; hsa-miR-371-5P, hsa-miR-423-5P, hsa-miR-638, hsa-miR-1224-3P and hsa-miR-663 that were differentially expressed in lupus nephritis across different racial groups and all specimen types tested. Hsa-miR-371-5P, hsa-miR-1224-3P and hsa-miR-423-5P, are reported here for the first time to be associated with lupus nephritis. Our work establishes EBV-transformed B cell lines as a useful model for the discovery of miRNA as biomarkers for SLE. Based on these findings, we postulate that these differentially expressed miRNA may be potential novel biomarkers for SLE as well as help elucidate pathogenic mechanisms of lupus nephritis. The investigation of miRNA profiles in SLE may lead to the discovery and development of novel methods to diagnosis, treat and prevent SLE. PMID:20485490

  7. Monocyte Chemotactic Protein-1, Fractalkine, and Receptor for Advanced Glycation End Products in Different Pathological Types of Lupus Nephritis and Their Value in Different Treatment Prognoses

    PubMed Central

    Lan, Lan; Han, Fei; Lang, Xiabing; Chen, Jianghua

    2016-01-01

    Background Early diagnosis is important for the outcome of lupus nephritis (LN). However, the pathological type of lupus nephritis closely related to the clinical manifestations; therefore, the treatment of lupus nephritis depends on the different pathological types. Objective To assess the level of monocyte chemotactic protein (MCP-1), fractalkine (Fkn), and receptor for advanced glycation end product (RAGE) in different pathological types of lupus nephritis and to explore the value of these biomarkers for predicting the prognosis of lupus nephritis. Methods Patients included in this study were assessed using renal biopsy. Class III and class IV were defined as the proliferative group, class V as non-proliferative group, and class V+III and class V+IV as the mixed group. During the follow-up, 40 of 178 enrolled patients had a poor response to the standard immunosuppressant therapy. The level of markers in the different response groups was tested. Results The levels of urine and serum MCP-1, urine and serum fractalkine, and serum RAGE were higher in the proliferative group, and lower in the non-proliferative group, and this difference was significant. The levels of urine and serum MCP-1 and serum RAGE were lower in the poor response group, and these differences were also significant. The relationship between urine MCP-1 and urine and serum fractalkine with the systemic lupus erythematosus disease activity index was evaluated. Conclusion The concentration of cytokines MCP-1, fractalkine, and RAGE may be correlated with different pathology type of lupus nephtitis. Urine and serum MCP-1 and serum RAGE may help in predicting the prognosis prior to standard immunosuppressant therapy. PMID:27458981

  8. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis

    PubMed Central

    Alba, P; Bento, L; Cuadrado, M; Karim, Y; Tungekar, M; Abbs, I; Khamashta, M; D'Cruz, D; Hughes, G

    2003-01-01

    Background: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial. Objective: To study the immunological and demographic factors associated with the development of LN. Patients and methods: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing. Results: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes. Conclusions: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN. PMID:12759294

  9. [Clinical guideline for the treatment of lupus nephritis and single-centre results of mycofenolate mofetil among patients with lupus nephritis in the National Institute of Rheumatology and Physiotherapy, Budapest].

    PubMed

    Szabó, Melinda Zsuzsanna; Kiss, Emese

    2016-08-01

    The authors present the latest guideline for the treatment of lupus nephritis and their own single-centre results with mycofenolate mofetil treated lupus nephritis. Lupus nephritis and mainly its proliferative form is a frequent and potentially life-threatening manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. The treatment of lupus nephritis greatly improved in the last decades; mycofenolate mofetil has become an alternative of cyclophosphamide both in remission induction and as a maintenance regimen as well in the treatment of Class III and IV glomerulonephritis. The authors ordered mycofenolate mofetil for 25 patients with lupus nephritis so far. Histologically most of them had Class III (A/C) or IV (A) glomerulonephritis (30-30%), and only 16% of the patients had renal impairment at that time. Mycofenolate mofetil given after glucocorticoid and cyclophosphamide induction therapy reduced the daily proteinuria from 3.18 grs to 1.06 grs. Complete remission could be achieved in 24% and partial remission in 48% of the patients. The authors conclude that mycofenolate mofetil is effective in the therapy of lupus nephritis. Orv. Hetil., 2016, 157(35), 1385-1393. PMID:27569461

  10. Mycophenolate mofetil versus azathioprine for maintenance treatment of lupus nephritis.

    PubMed

    Kaballo, Babikir G; Ahmed, Ahmed Elias; Nur, Musa Mohammed; Khalid, Ismail Osman; Abu-Aisha, Hasan

    2016-01-01

    To compare the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) drugs in the maintenance therapy of lupus nephritis (LN) patients, we studied 81 Sudanese patients with LN (32 in Class III, 34 in Class IV, and 15 in combined Class V + IV of the ISN/RPS 2003 Classification). All patients received induction therapy consisting of monthly intravenous pulse doses of cyclophosphamide (CYC) (500 mg/m 2 of body-surface area) for six months, plus three consecutive pulses of intravenous methylprednisolone 15 mg/kg/day of body weight (maximum 500 mg). Subsequently, 41 (50.6%) patients were randomized into a group that received oral MMF (22 mg/kg/day), and 40 (49.4%) patients randomized to a group that received oral AZA (2 mg/kg/day). All patients initially received oral prednisone (1 mg/kg of body weight daily) for four weeks. The baseline characteristics of the two groups were similar. Total remission rate was 75.3% (80.5% in MMF and 70% in AZA), complete remission rate of 54.3% (56.1% with MMF and 52.5% with AZA), and a partial remission rate of 21% (24.4% with MMF and 17.5% with AZA) over 29 months. During maintenance therapy, six patients died (four in the AZA group and two in the MMF group), and end-stage renal disease (ESRD) developed in five patients (three in the AZA group and two in the MMF group). During the 36-months of the study, both groups had comparable event-free survival rate for the composite end point of death or ESRD and rate of relapse-free survival. Furthermore, both groups had no significant differences in terms of frequency of hospitalization, amenorrhea, infection, nausea, and vomiting. We conclude that our study showed that short-term therapy with intravenous CYC followed by maintenance therapy with oral MMF or AZA had similar efficacy and safety for the treatment of patients with moderate to severe LN. PMID:27424688

  11. The SLAM family member CD48 (Slamf2) protects lupus-prone mice from autoimmune nephritis

    PubMed Central

    Koh, Anna E.; Njoroge, Sarah W.; Feliu, Marianela; Cook, Alexis; Selig, Martin K.; Latchman, Yvette E.; Sharpe, Arlene H.; Colvin, Robert B.; Paul, Elahna

    2011-01-01

    Polymorphisms in the SLAM family of leukocyte cell surface regulatory molecules have been associated with lupus-like phenotypes in both humans and mice. The murine Slamf gene cluster lies within the lupus-associated Sle1b region of mouse chromosome 1. Non-autoreactive C57BL/6 (B6) mice that have had this region replaced by syntenic segments from other mouse strains (i.e. 129, NZB and NZW) are B6 congenic strains that spontaneously produce non-nephritogenic lupus-like autoantibodies. We have recently reported that genetic ablation of the SLAM family member CD48 (Slamf2) drives full-blown autoimmune disease with severe proliferative glomerulonephritis (CD48GN) in B6 mice carrying 129 sequences of the Sle1b region (B6.129CD48-/-). We also discovered that BALB/c mice with the same 129-derived CD48-null allele (BALB.129CD48-/-) have neither nephritis nor anti-DNA autoantibodies, indicating that strain specific background genes modulate the effects of CD48 deficiency. Here we further examine this novel model of lupus nephritis in which CD48 deficiency transforms benign autoreactivity into fatal nephritis. CD48GN is characterized by glomerular hypertrophy with mesangial expansion, proliferation and leukocytic infiltration. Immune complexes deposit in mesangium and in sub-endothelial, sub-epithelial and intramembranous sites along the glomerular basement membrane. Afflicted mice have low grade proteinuria, intermittent hematuria and their progressive renal injury manifests with elevated urine NGAL levels and with uremia. In contrast to the lupus-like B6.129CD48-/- animals, neither BALB.129CD48-/- mice nor B6 × BALB/c F1.129CD48-/- progeny have autoimmune traits, indicating that B6-specific background genes modulate the effect of CD48 on lupus nephritis in a recessive manner. PMID:21561736

  12. Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans.

    PubMed

    Liu, Kui; Li, Quan-Zhen; Delgado-Vega, Angelica M; Abelson, Anna-Karin; Sánchez, Elena; Kelly, Jennifer A; Li, Li; Liu, Yang; Zhou, Jinchun; Yan, Mei; Ye, Qiu; Liu, Shenxi; Xie, Chun; Zhou, Xin J; Chung, Sharon A; Pons-Estel, Bernardo; Witte, Torsten; de Ramón, Enrique; Bae, Sang-Cheol; Barizzone, Nadia; Sebastiani, Gian Domenico; Merrill, Joan T; Gregersen, Peter K; Gilkeson, Gary G; Kimberly, Robert P; Vyse, Timothy J; Kim, Il; D'Alfonso, Sandra; Martin, Javier; Harley, John B; Criswell, Lindsey A; Wakeland, Edward K; Alarcón-Riquelme, Marta E; Mohan, Chandra

    2009-04-01

    Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus. PMID:19307730

  13. Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

    PubMed Central

    Liu, Kui; Li, Quan-Zhen; Delgado-Vega, Angelica M.; Abelson, Anna-Karin; Sánchez, Elena; Kelly, Jennifer A.; Li, Li; Liu, Yang; Zhou, Jinchun; Yan, Mei; Ye, Qiu; Liu, Shenxi; Xie, Chun; Zhou, Xin J.; Chung, Sharon A.; Pons-Estel, Bernardo; Witte, Torsten; de Ramón, Enrique; Bae, Sang-Cheol; Barizzone, Nadia; Sebastiani, Gian Domenico; Merrill, Joan T.; Gregersen, Peter K.; Gilkeson, Gary G.; Kimberly, Robert P.; Vyse, Timothy J.; Kim, Il; D’Alfonso, Sandra; Martin, Javier; Harley, John B.; Criswell, Lindsey A.; Wakeland, Edward K.; Alarcón-Riquelme, Marta E.; Mohan, Chandra

    2009-01-01

    Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody–induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody–induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody–induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody–induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody–induced nephritis and lupus. PMID:19307730

  14. "Kill" the messenger: Targeting of cell-derived microparticles in lupus nephritis.

    PubMed

    Nielsen, Christoffer T; Rasmussen, Niclas S; Heegaard, Niels H H; Jacobsen, Søren

    2016-07-01

    Immune complex (IC) deposition in the glomerular basement membrane (GBM) is a key early pathogenic event in lupus nephritis (LN). The clarification of the mechanisms behind IC deposition will enable targeted therapy in the future. Circulating cell-derived microparticles (MPs) have been proposed as major sources of extracellular autoantigens and ICs and triggers of autoimmunity in LN. The overabundance of galectin-3-binding protein (G3BP) along with immunoglobulins and a few other proteins specifically distinguish circulating MPs in patients with systemic lupus erythematosus (SLE), and this is most pronounced in patients with active LN. G3BP co-localizes with deposited ICs in renal biopsies from LN patients supporting a significant presence of MPs in the IC deposits. G3BP binds strongly to glomerular basement membrane proteins and integrins. Accordingly, MP surface proteins, especially G3BP, may be essential for the deposition of ICs in kidneys and thus for the ensuing formation of MP-derived electron dense structures in the GBM, and immune activation in LN. This review focuses on the notion of targeting surface molecules on MPs as an entirely novel treatment strategy in LN. By targeting MPs, a double hit may be achieved by attenuating both the autoantigenic fueling of immune complexes and the triggering of the adaptive immune system. Thereby, early pathogenic events may be blocked in contrast to current treatment strategies that primarily target and modulate later events in the cellular and humoral immune response. PMID:26970484

  15. Case report: successful treatment of membranous lupus nephritis with belimumab in an African female immigrant.

    PubMed

    De Scheerder, Marie-Angélique; Boey, O; Mahieu, E; Vanuytsel, J; Bogaert, Anne-Marie

    2016-06-01

    We describe the case of a 26-year-old African female who was treated successfully with belimumab in a case of severe membranous lupus nephritis and retinal vasculitis, resistant to first line therapy. She presented initially with chronic dacryoadenitis and screening showed nephrotic-range proteinuria. Biopsy of the kidney confirmed the diagnosis of membranous lupus nephritis. Clinical features (joint pain, dacryoadenitis, retinal vasculitis and lupus nephritis) in combination with serology (positive anti-double-stranded DNA (ds-DNA) antibodies, hypocomplementemia) confirmed the diagnosis of systemic lupus erythematosus (SLE). Treatment was immediately initiated with glucocorticosteroids (GCS), mycophenolate mofetil (MMF) and hydroxychloroquine sulphate (Plaquenil®). Tacrolimus was associated but no effect was observed with the proteinuria remaining in the nephrotic range and secondary effects of the glucocorticosteroids becoming a real concern. The patient was started on add-on belimumab with quasi-immediate effect on the proteinuria, making it possible to decrease the dosage of the other immunosuppressants and gradually stop them, even the GCS. The patient is currently in complete remission after 3 years of treatment with belimumab. We were able to stop immunosuppressive treatment but will keep her on antimalarial treatment as the most recent guidelines in treatment of SLE recommend. PMID:26712500

  16. B cells are required for lupus nephritis in the polygenic, Fas-intact MRL model of systemic autoimmunity.

    PubMed

    Chan, O T; Madaio, M P; Shlomchik, M J

    1999-10-01

    B cells are required for both the expression of lupus nephritis and spontaneous T cell activation/memory cell accumulation in MRL-Faslpr mice (MRL/lpr). Autoimmunity in the MRL/lpr strain is the result of Fas-deficiency and multiple background genes; however, the precise roles of background genes vs Fas-deficiency have not been fully defined. Fas-deficiency (i.e., the lpr defect) is required in B cells for optimal autoantibody expression, raising the possibility that the central role for B cells in MRL/lpr mice may not extend to MRL/+ mice and, thus, to lupus models that do not depend on Fas-deficiency ("polygenic lupus"). To address this issue, B cell-deficient, Fas-intact MRL/+ mice (JHd-MRL/) were created; and disease was evaluated in aged animals (>9 mo). The JHd-MRL/+ animals did not develop nephritis or vasculitis at a time when the B cell-intact littermates had severe disease. In addition, while activated/memory CD4+ and CD8+ T cells accumulated in B cell-intact mice, such accumulation was substantially inhibited in the absence of B cells. This effect appeared to be restricted to the MRL strain because it was not seen in B cell-deficient BALB/c mice (JHd-BALB) of similar ages. The results indicate that B cells are essential in promoting systemic autoimmunity in a Fas-independent model. Therefore, B cells have an important role in pathogenesis, generalizable to lupus models that depend on multiple genes even when Fas expression is intact. The results provide further rationale for B cell suppression as therapy for systemic lupus erythematosus. PMID:10490951

  17. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway.

    PubMed

    Liu, Zhiqin; Xue, Leixi; Liu, Zhichun; Huang, Jun; Wen, Jian; Hu, Ji; Bo, Lin; Yang, Ru

    2016-01-01

    This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells) were used for in vitro experiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK-shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-β1, p-p38 MAPK, p-Smad2, COL-1, and α-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-β1, p-p38 MAPK, p-SMAD2, α-SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E-cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-β1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway. PMID:27365897

  18. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway

    PubMed Central

    Liu, Zhiqin; Xue, Leixi; Liu, Zhichun; Huang, Jun; Wen, Jian; Hu, Ji; Bo, Lin; Yang, Ru

    2016-01-01

    This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells) were used for in vitro experiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK-shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-β1, p-p38 MAPK, p-Smad2, COL-1, and α-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-β1, p-p38 MAPK, p-SMAD2, α-SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E-cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-β1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway. PMID:27365897

  19. Multi-antibody composition in lupus nephritis: isotype and antigen specificity make the difference.

    PubMed

    Bonanni, Alice; Vaglio, Augusto; Bruschi, Maurizio; Sinico, Renato Alberto; Cavagna, Lorenzo; Moroni, Gabriella; Franceschini, Franco; Allegri, Landino; Pratesi, Federico; Migliorini, Paola; Candiano, Giovanni; Pesce, Giampaola; Ravelli, Angelo; Puppo, Francesco; Martini, Alberto; Tincani, Angela; Ghiggeri, Gian Marco

    2015-08-01

    Research on autoimmune processes involved in glomerulonephritis has been for years based on experimental models. Recent progress in proteomics has radically modified perspectives: laser microdissection and proteomics were crucial for an in vivo analysis of autoantibodies eluted from human biopsies. Lupus nephritis has been the subject of recent independent researches. Main topics have been the definition of renal autoimmune components in human lupus biopsies; methods were laser capture of glomeruli and/or of single cells (CD38+ or Ki-67+) from tubulointerstitial areas as starting step followed by elution and characterization of renal antibodies by proteomics. The innovative approach highlighted different panels of autoantibodies deposited in glomeruli and in tubulo-interstitial areas that actually represented the unique autoimmune components in these patients. IgG2 was the major isotype; new podocyte proteins (αenolase, annexin AI) and already known implanted molecules (DNA, histone 3, C1q) were their target antigens in glomeruli. Vimentin was the antigen in tubulo-interstitial areas. Matching renal autoantibodies with serum allowed the definition of a typical autoantibody serum map that included the same anti-αenolase, anti-annexin AI, anti-DNA, and anti-histone 3 IgG2 already detected in renal tissue. Serum levels of specific autoantibodies were tenfold increased in patients with lupus nephritis allowing a clear differentiation from both rheumatoid arthritis and other glomerulonephritis. In all cases, targeted antigens were characterized as components of lupus NETosis. Matching renal/serum autoantibody composition in vivo furnishes new insights on human lupus nephritis and allows to refine composition of circulating antibodies in patients with lupus. A thoughtful passage from bench to bedside of new knowledge would expand our clinical and therapeutic opportunities. PMID:25888464

  20. A Rare Presentation of Lupus Nephritis Flare up with Posterior Reversible Leucoencephalopathy.

    PubMed

    Mani, S Hima; Shivaprasad, S M; Umesh, L

    2016-01-01

    Systemic lupus erythematosus (SLE) is associated with various neurologic or psychiatric abnormalities and Posterior Reversible Leuco Encephalopathy Syndrome (PRES) is very rare neurological manifestation in SLE. PRES is associated with various clinical manifestations, like, seizures, visual loss, headaches, vomiting altered mental status and rarely focal neurological deficits. Other predisposing condition associated with PRES is eclampsia, accelerated hypertension, uraemia, transplantation, autoimmune diseases and/or use of immunosuppressive drugs. It is important to recognise PRES since it is a potentially reversible. We describe an unusual case of PRES caused by uraemia during lupus flare up in a patient with biopsy proven class IV lupus nephritis who presented with features of asymmetrical quadriparesis which completely reversed after haemodialysis sessions and treating lupus flare up. In our case she presented with quadriparesis which is a rare presentation and hypertensive encephalopathy was not present. PMID:26894110

  1. Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis

    PubMed Central

    SALIMI, SAEEDEH; NOORA, MEHRANGIZ; NABIZADEH, SIMA; REZAEI, MAHNAZ; SHAHRAKI, HOSSAIN; MILAD, MOHAMMADOO-KHORASSANI; NAGHAVI, ANOOSH; FARAJIAN-MASHHADI, FARZANEH; ZAKERI, ZAHRA; SANDOUGHI, MAHNAZ

    2016-01-01

    Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6±22 vs. 35.6±15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and SLE susceptibility. PMID:26998275

  2. Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

    PubMed

    Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

    2012-05-01

    Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results. PMID:21258801

  3. Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

    PubMed Central

    Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

    2015-01-01

    Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

  4. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis.

    PubMed

    Dieker, Jürgen; Schlumberger, Wolfgang; McHugh, Neil; Hamann, Philip; van der Vlag, Johan; Berden, Jo H

    2015-11-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system. PMID:26597199

  5. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

    PubMed

    Bastian, H M; Roseman, J M; McGwin, G; Alarcón, G S; Friedman, A W; Fessler, B J; Baethge, B A; Reveille, J D

    2002-01-01

    The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95

  6. Analysis of the effectiveness and safety of rituximab in patients with refractory lupus nephritis: a chart review.

    PubMed

    Contis, Anne; Vanquaethem, Helene; Truchetet, Marie-Elise; Couzi, Lionel; Rigothier, Claire; Richez, Christophe; Lazaro, Estibaliz; Duffau, Pierre

    2016-02-01

    Lupus nephritis is a life-threatening complication of systemic lupus erythematosus. The standard treatment for this condition, including corticosteroids and cyclophosphamide, results in a 70 % remission rate at 12 months, but it is also associated with significant morbidity. Rituximab, a chimeric anti-CD20 antibody, could be useful, given the central role of B cells in the pathogenesis of systemic lupus erythematosus. Case reports and retrospective series have reported that rituximab is effective for refractory lupus nephritis. However, the double-blind, placebo-controlled LUNAR trial failed to meet its end point. We studied clinical, biological, and immunological data on 17 patients who received rituximab as an induction treatment for refractory lupus nephritis at the University Hospital Center of Bordeaux. A complete treatment response was defined as a normal serum creatinine with inactive urinary sediment and 24-h urinary albumin <0.5 g and a partial response (PR) as a >50 % improvement in all of the renal parameters that were abnormal at baseline, with no deterioration in any parameter. Seventeen patients received rituximab as induction treatment for lupus nephritis refractory to standard treatment by cyclophosphamide. After a follow-up of 12 months, complete or partial renal remission was achieved in 53 % patients. Rituximab therapy resulted in a significant improvement in proteinuria and steroid dose tapering in all patients. Rituximab should be considered as a treatment option for refractory lupus glomerulonephritis. PMID:26762196

  7. Elevated expressions of myeloid-related proteins-8 and -14 are danger biomarkers for lupus nephritis.

    PubMed

    Tantivitayakul, P; Benjachat, T; Somparn, P; Leelahavanichkul, A; Kittikovit, V; Hirankarn, N; Pisitkun, T; Avihingsanon, Y

    2016-01-01

    Myeloid-related proteins, MRP-8 and -14, which have been identified as molecules that mediate the danger signaling in innate immune response, are also known as the DAMPs (damage associated molecular pattern molecules). The proteins were found in infiltrating macrophages and neutrophils at inflammatory sites. Their expression was correlated with severe forms of glomerulonephritis. Therefore, this study examined whether or not MRP-8 and -14 can be used as biomarkers for identifying severely active lupus nephritis (LN). Total blood leukocyte samples and renal biopsy tissues from a prospective cohort of LN patients were used to determine mRNA and protein expression levels of MRP-8 and -14. The mRNA levels of MRP-8 and -14 in total blood leukocytes were significantly higher in active LN patients than quiescent LN patients and healthy controls. Moreover, the mRNA levels of MRP-8 and -14 in the total blood leukocytes and kidney tissues were significantly correlated with therapeutic response and the mRNA expression levels in the kidney were associated with an early loss of the kidney function. MRP-8 and -14 can be used as non-invasive prognostic biomarkers in patients with LN. PMID:26223295

  8. Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

    PubMed

    Benjachat, Thitima; Tongyoo, Pumipat; Tantivitayakul, Pornpen; Somparn, Poorichaya; Hirankarn, Nattiya; Prom-On, Santitham; Pisitkun, Prapaporn; Leelahavanichkul, Asada; Avihingsanon, Yingyos; Townamchai, Natavudh

    2015-01-01

    The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR) gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy. PMID:26110394

  9. Kidney Expression of Toll Like Receptors in Lupus Nephritis: Quantification and Clinicopathological Correlations

    PubMed Central

    Miranda, Francesca; Bombardieri, Michele; Valesini, Guido

    2016-01-01

    Objective. The study aimed at locating and quantifying Toll Like Receptor (TLR) 3, 7, 8, and 9 expression in kidney of patients with lupus nephritis (LN) and correlating them with clinicopathological features. Methods. Kidney sections from 26 LN patients and 4 controls were analyzed by immunohistochemistry using anti-human TLR3, TLR7, TLR8, and TLR9 polyclonal antibodies; the number of TLR-positive nuclei/mm2 was evaluated on digitalized images. Results. Compared to controls, LN showed a significantly higher amount of glomerular and tubulointerstitial TLR9 (p = 0.003 and p = 0.007), whole and tubulointerstitial TLR3 (p = 0.026 and p = 0.031), and a higher tubulointerstitial TLR7 (p = 0.022). TLR9 positively correlated with activity index (p = 0.0063) and tubular TLR7 with chronicity index (p = 0.026). TLR9 positively correlated with Renal-SLEDAI (p = 0.01). Conclusions. This is the first study quantifying kidney expressions of TLRs in LN patients; the results show an overexpression of TLR3, TLR7, and TLR9 and demonstrate a correlation with clinicopathological indices supporting a role of these mediators in the pathogenesis of LN.

  10. Factors associated with chronic renal failure in 121 patients with diffuse proliferative lupus nephritis: a case-control study.

    PubMed

    Arce-Salinas, C A; Villa, A R; Martínez-Rueda, J O; Muñoz, L; Cardiel, M H; Alcocer-Varela, J; Alarcón-Segovia, D

    1995-06-01

    Lupus nephritis remains an important problem in patients with systemic lupus erythematosus (SLE). Some patients with diffuse proliferative lupus nephritis (DPLN) develop chronic renal failure (CRF). A case-control study was designed to determine the variables associated with CRF in patients with DPLN. We studied 121 patients with biopsy-proven DPLN seen in our institution from 1970 to 1988. There were 34 patients who developed CRF, the remaining were their controls. Clinical charts were reviewed and a pathologist re-scored blindly both activity and chronicity indices. The mean of age at SLE onset was 24.1 +/- 7.9 years; the mean disease duration was 9.2 +/- 6.1 years for controls and 6.1 +/- 5 years for patients. The main variables associated with CRF were male sex. HR (hazard ratio): 12.6 (95% CI 1.6-98.2); activity index, HR 2.59 (1.07-6.3); severe infections, HR 2.9 (1.2-7.3): number of antihypertensive drugs, HR 2.5 (1.4-4.7); cellular crescents, HR 1.6 (1.2-2): and interstitial inflammation, HR 2.7 (1.5-5.1). A protective effect was observed with longer use of < or = 20 mg of prednisone, HR 0.53 (95% CI 0.34-08): azathioprine, HR 0.6 (0.4-0.8); and length of formal education. HR 0.3 (0.09-0.94). Our results indicate that maleness, activity index, extracapillary proliferation and interstitial inflammation, as well as hypertension and severe infections associate with CRF in patients with DPLN, and treatment and higher education, perhaps through better therapeutic compliance, may be protective. PMID:7655489

  11. CCR1 inhibition ameliorates the progression of lupus nephritis in NZB/W mice.

    PubMed

    Bignon, Alexandre; Gaudin, Françoise; Hémon, Patrice; Tharinger, Hugo; Mayol, Katia; Walzer, Thierry; Loetscher, Pius; Peuchmaur, Michel; Berrebi, Dominique; Balabanian, Karl

    2014-02-01

    Systemic lupus erythematosus is a chronic inflammatory autoimmune disease, the development of which is characterized by a progressive loss of renal function. Such dysfunction is associated with leukocyte infiltration in the glomerular and tubulointerstitial compartments in both human and experimental lupus nephritis. In this study, we investigated the role of the Ccr1 chemokine receptor in this infiltration process during the progression of nephritis in the lupus-prone New Zealand Black/New Zealand White (NZB/W) mouse model. We found that peripheral T cells, mononuclear phagocytes, and neutrophils, but not B cells, from nephritic NZB/W mice were more responsive to Ccr1 ligands than the leukocytes from younger prenephritic NZB/W mice. Short-term treatment of nephritic NZB/W mice with the orally available Ccr1 antagonist BL5923 decreased renal infiltration by T cells and macrophages. Longer Ccr1 blockade decreased kidney accumulation of effector/memory CD4(+) T cells, Ly6C(+) monocytes, and both M1 and M2 macrophages; reduced tubulointerstitial and glomerular injuries; delayed fatal proteinuria; and prolonged animal lifespan. In contrast, renal humoral immunity was unaffected in BL5923-treated mice, which reflected the unchanged numbers of infiltrated B cells in the kidneys. Altogether, these findings define a pivotal role for Ccr1 in the recruitment of T and mononuclear phagocyte cells to inflamed kidneys of NZB/W mice, which in turn contribute to the progression of renal injury. PMID:24367031

  12. Organ involvement other than lupus nephritis in childhood-onset systemic lupus erythematosus.

    PubMed

    Huggins, J L; Holland, M J; Brunner, H I

    2016-07-01

    In this review we critically analyze pulmonary, gastrointestinal and cardiac manifestations of childhood-onset systemic lupus erythematosus (cSLE). Clinical manifestations of these organ systems may be the initial manifestation of cSLE; frequently occur with very active cSLE; and are potential life-threatening manifestations often presenting to the emergency department and requiring admission to the intensive care unit. Early recognition and treatment of the pulmonary, gastrointestinal and cardiac manifestations of cSLE will result in improved prognosis and better outcomes. PMID:27252262

  13. Tacrolimus use in lupus nephritis: A systematic review and meta-analysis.

    PubMed

    Hannah, Jennifer; Casian, Alina; D'Cruz, David

    2016-01-01

    There is growing interest in the role of tacrolimus as a potential therapeutic agent in SLE. This systematic review and meta-analysis evaluates the evidence for tacrolimus use in the management of lupus nephritis. Thirteen controlled studies were identified (9 suitable for inclusion), using Cochrane database, SCOPUS, Web of Science and OVID (MEDLINE and EMBASE). Data on complete and partial remission rates, proteinuria reduction and adverse events was extracted and analysed using RevMan software. The meta-analysis showed that overall tacrolimus is more effective at inducing complete renal remission than IVCYC (p=0.004), but there is no significant difference compared to MMF (p=0.87). Multi-target TAC+MMF therapy is more effective than IVCYC only when partial remission is included (p=0.0006). Frequency of key adverse effects seems comparable to other agents used in the management of lupus nephritis with fewer gastrointestinal side effects, leukopenia, menstrual disorders, infections and episodes of liver dysfunction reported, but more new onset hypertension and hyperglycaemia. Mortality was lower in the tacrolimus groups, but this was not statistically significant (p=0.15). Tacrolimus may be more effective at reducing proteinuria, but again this was not statistically significant. There are no controlled trials looking at use in pregnancy or juvenile patients, however case reports suggest potential efficacy and safety. In conclusion, in moderately severe lupus nephritis, there is some evidence supporting efficacy of tacrolimus or multi-target TAC+MMF over IVCYC, but no evidence supporting tacrolimus over MMF. Tacrolimus may be more effective at reducing proteinuria, having potential implications for long-term outcome. Key limitations of this study are the lack of long-term outcome data and the lack of high quality, large, blinded controlled trials in multi-ethnic groups. PMID:26427983

  14. 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

  15. 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

  16. 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

  17. Comparison of Renal Response Parameters for Juvenile Membranous Plus Proliferative Lupus Nephritis Versus Isolated Proliferative Lupus Nephritis: A Cross-Sectional Analysis of the CARRA Registry

    PubMed Central

    Boneparth, Alexis; Ilowite, Norman T.

    2014-01-01

    Lupus nephritis (LN) affects many patients with juvenile systemic lupus erythematosus (SLE) and is a significant cause of disease morbidity. Membraneous plus proliferative LN (M+PLN) may represent a more difficult to treat subtype of juvenile LN, compared to isolated proliferative LN (PLN.) In this retrospective observational study, we utilized data from the Childhood Arthritis and Rheumatism Research Alliance (CARRA) registry to compare response rates for pediatric M+PLN versus PLN. Response was assessed at the most recent CARRA registry visit gathered ≥ 6 months after diagnostic kidney biopsy. Estimated glomerular filtration rate (GFR) less than 90 ml/min/1.73m2, indicating renal insufficiency, was found in 16.1% of patients with M+PLN and 6.1% of patients with PLN (P=0.071). We found no significant difference in achievement of response in either hematuria or proteinuria between PLN and M+PLN groups or between subgroups determined by presence of class III vs. class IV proliferative disease. Exposure rates to mycophenolate, cyclophosphamide, and rituximab were similar between groups. Future studies will be necessary to correlate pediatric LN renal histology data with treatment response as well as other disease outcome measures. PMID:24729278

  18. Comparison of renal response parameters for juvenile membranous plus proliferative lupus nephritis versus isolated proliferative lupus nephritis: a cross-sectional analysis of the CARRA Registry.

    PubMed

    Boneparth, A; Ilowite, N T

    2014-08-01

    Lupus nephritis (LN) affects many patients with juvenile systemic lupus erythematosus (SLE) and is a significant cause of disease morbidity. Membranous plus proliferative LN (M + PLN) may represent a more difficult to treat subtype of juvenile LN, compared to isolated proliferative LN (PLN). In this retrospective observational study, we utilized data from the Childhood Arthritis and Rheumatism Research Alliance (CARRA) registry to compare response rates for pediatric M + PLN versus PLN. Response was assessed at the most recent CARRA registry visit gathered ≥6 months after diagnostic kidney biopsy. Estimated glomerular filtration rate (GFR) less than 90 ml/min/1.73 m(2), indicating renal insufficiency, was found in 16.1% of patients with M + PLN and 6.1% of patients with PLN (P = 0.071). We found no significant difference in achievement of response in either hematuria or proteinuria between PLN and M + PLN groups or between subgroups determined by presence of class III vs. class IV proliferative disease. Exposure rates to mycophenolate, cyclophosphamide, and rituximab were similar between groups. Future studies will be necessary to correlate pediatric LN renal histology data with treatment response as well as other disease outcome measures. PMID:24729278

  19. DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis.

    PubMed

    Cai, Minchao; Zhou, Tong; Wang, Xuan; Shang, Minghua; Zhang, Yueyue; Luo, Maocai; Xu, Chundi; Yuan, Weijie

    2016-03-01

    Podocytes, the main target of immune complex, participate actively in the development of glomerular injury as immune cells. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune molecular that has an immune recognition function, and is involved in mediation of cell adhesion and immunoregulation. Here we explored the expression of DC-SIGN on podocytes and its role in immune and inflammatory responses in lupus nephritis (LN). Expression of DC-SIGN and immunoglobulin (Ig)G1 was observed in glomeruli of LN patients. DC-SIGN was co-expressed with nephrin on podocytes. Accompanied by increased proteinuria of LN mice, DC-SIGN and IgG1 expressions were observed in the glomeruli from 20 weeks, and the renal function deteriorated up to 24 weeks. Mice with anti-DC-SIGN antibody showed reduced proteinuria and remission of renal function. After the podocytes were stimulated by serum of LN mice in vitro, the expression of DC-SIGN, major histocompatibility complex (MHC) class II and CD80 was up-regulated, stimulation of T cell proliferation was enhanced and the interferon (IFN)-γ/interleukin (IL)-4 ratio increased. However, anti-DC-SIGN antibody treatment reversed these events. These results suggested that podocytes in LN can exert DC-like function through their expression of DC-SIGN, which may be involved in immune and inflammatory responses of renal tissues. However, blockage of DC-SIGN can inhibit immune functions of podocytes, which may have preventive and therapeutic effects. PMID:26440060

  20. Comparison of Outcomes between Individuals with Pure and Mixed Lupus Nephritis: A Retrospective Study

    PubMed Central

    Ilori, Titilayo O.; Enofe, Nosayaba; Oommen, Anju; Cobb, Jason; Navarrete, Jose; Adedinsewo, Demilade A.; Oshikoya, Oluwatobiloba; Fevrier, Helene; Farris, Alton B.; Plantinga, Laura; Ojo, Akinlolu O.

    2016-01-01

    Introduction Lupus nephritis (LN) is a serious organ manifestation of systemic lupus erythematosus. Histologic overlap is relatively common in the six pathologic classes (I to VI) of LN. For example, mixed proliferative LN (MPLN) often includes features of classes III & V or classes IV & V combined. We performed a comparative evaluation of renal outcomes in patients with MPLN to patients with pure proliferative LN (PPLN) against pre-specified renal outcomes, and we also identified predictor of clinical outcomes among those with PPLN and MPLN. Hypothesis Individuals with MPLN will have worse short-term renal outcomes compared to those with PPLN. Methods We retrospectively reviewed 278 adult LN patients (≥18 years old) identified from an Emory University Hospital registry of native renal biopsies performed between January 2000 and December 2011. The final analytic sample consisted of individuals with a diagnosis of PPLN (n = 60) and MPLN (n = 96). We analyzed differences in clinical and laboratory characteristics at baseline. We also assessed associations between LN category and renal outcomes (complete remission and time to ESRD) with logistic and Cox proportional hazards models within two years of baseline. Results The study population was predominantly female (83.97%) and African American (71.8%) with a mean age of 33.4 years at baseline. Over a median follow up of 1.02 years, we did not find any statistically significant associations between MPLN and the development of ESRD or remission when compared to patients with PPLN (adjusted HR = 0.30, 95% CI = 0.07, 1.26). Conclusion There was no association between mixed or pure histopathologic features of LN at presentation and rate of complete or partial remission but higher baseline eGFR was associated with a lower probability of complete remission among patients with lupus nephritis. PMID:27304068

  1. Clinical outcomes of kidney transplants on patients with end-stage renal disease secondary to lupus nephritis, polycystic kidney disease and diabetic nephropathy

    PubMed Central

    Nieto-Ríos, John Fredy; Builes-Rodriguez, Sheila Alexandra; Restrepo-Correa, Ricardo Cesar; Aristizabal-Alzate, Arbey; Ocampo-Kohn, Catalina; Serna-Campuzano, Angélica; Cardona-Díaz, Natalia; Giraldo-Ramirez, Nelson Darío; Zuluaga-Valencia, Gustavo Adolfo

    2016-01-01

    Background: Patients with lupus nephritis could progress to end-stage renal disease (10-22%); hence, kidney transplants should be considered as the treatment of choice for these patients. Objective: To evaluate the clinical outcomes after kidney transplants in patients with chronic kidney diseases secondary to lupus nephritis, polycystic kidney disease and diabetes nephropathy at Pablo Tobon Uribe Hospital. Methods: A descriptive and retrospective study performed at one kidney transplant center between 2005 and 2013. Results: A total of 136 patients, 27 with lupus nephritis (19.9%), 31 with polycystic kidney disease (22.8%) and 78 with diabetes nephropathy (57.4%), were included in the study. The graft survivals after one, three and five years were 96.3%, 82.5% and 82.5% for lupus nephritis; 90%, 86% and 76.5% for polycystic kidney disease and 91.7%, 80.3% and 67.9% for diabetes nephropathy, respectively, with no significant differences (p= 0.488); the rate of lupus nephritis recurrence was 0.94%/person-year. The etiology of lupus vs diabetes vs polycystic disease was not a risk factor for a decreased time of graft survival (Hazard ratio: 1.43; 95% CI: 0.52-3.93). Conclusion: Kidney transplant patients with end stage renal disease secondary to lupus nephritis has similar graft and patient survival success rates to patients with other kidney diseases. The complication rate and risk of recurrence for lupus nephritis are low. Kidney transplants should be considered as the treatment of choice for patients with end stage renal disease secondary to lupus nephritis. PMID:27226665

  2. Renal interstitial mast cell count is significantly higher in membranoproliferative glomerulonephritis than in class IV lupus nephritis.

    PubMed

    Kaczmarczyk, Karolina; Musiał, Jacek; Soja, Jerzy; Kuźniewski, Marek; Gala-Błądzińska, Agnieszka; Białas, Magdalena; Okoń, Krzysztof

    2015-06-01

    Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; in LN class IV morphologic lesions may be similar to the lesions in primary membranoproliferative glomerulonephritis (MPGN). The aim of the study was to compare the counts of tryptase-positive and chymase-positive mast cells between LN class IV and MPGN. The material consisted of 61 renal biopsies: 32 with lupus nephritis class IV, and 29 with membranoproliferative glomerulonephritis. Chymase- and tryptase-positive cells were stained by immunohistochemistry and subsequently counted. The mean count of chymase-positive mast cells was 21.94 for the whole group, 12.66 for LN class IV and 32.18 for MPGN. The mean count of tryptase-positive cells was 34.94 hpf for the entire group, 22.98 for LN class IV and 48. 13 for MPGN. The differences between lupus nephritis and membranoproliferative glomerulonephritis were significant both for chymase- and tryptase-positive cells. Both chymase-positive MC counts and tryptase-positive MC counts correlated with relative interstitial volume (RIV) (R=0.35 and R=0.28, respectively) and with creatinine level (R=0.35 and R=0.43, respectively). There was also a significant correlation between age, creatinine level and RIV (R=0.28 and R=0.26, respectively). PMID:26247528

  3. Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice

    PubMed Central

    Schaper, Fleur; van Timmeren, Mirjan M; Petersen, Arjen; Horst, Gerda; Bijl, Marc; Limburg, Pieter C; Westra, Johanna; Heeringa, Peter

    2016-01-01

    High mobility group box 1 (HMGB1) is a nuclear DNA binding protein that acts as an alarmin when secreted. HMGB1 is increased in systemic lupus erythematosus and might represent a potential therapeutic target. We investigated whether treatment with an anti-HMGB1 antibody affects the development of lupus nephritis in MRL/lpr mice. Seven-week-old MRL/lpr mice were injected intraperitoneally twice weekly for 10 wks with 50 μg monoclonal anti-HMGB1 (2G7, mouse IgG2b) (n = 12) or control antibody (n = 11). Control MRL/MPJ mice (n = 10) were left untreated. Every 2 wks, blood was drawn and urine was collected at wk 7, 11 and 17. Mice were sacrificed at 17 wks for complete disease evaluation. Plasma HMGB1 and anti-HMGB1 levels were increased in MRL/lpr mice compared with control MRL/MPJ mice. There were no differences in albuminuria, urine HMGB1 and plasma levels of complement C3, anti-dsDNA and proinflammatory cytokines between untreated and treated mice at any time point. Lupus nephritis of mice treated with anti-HMGB1 monoclonal antibody (mAb) was classified as class III (n = 3) and class IV (n = 9), while mice treated with control mAb were classified as class II (n = 4), class III (n = 2) and class IV (n = 5). IgG and C3 deposits in kidneys were similar in mice treated with anti-HMGB1 mAb or control mAb. In conclusion, treatment with monoclonal anti–HMGB-1 antibody 2G7 does not affect development of lupus nephritis, disease progression or proinflammatory cytokine levels in MRL/lpr mice. This result indicates that blocking of HMGB1 by this neutralizing antibody does not affect lupus nephritis in MRL/lpr mice. PMID:26837069

  4. Early-onset neutropenia induced by rituximab in a patient with lupus nephritis and hemolytic anemia.

    PubMed

    Arroyo-Ávila, Mariangelí; Fred-Jiménez, Ruth M; Vilá, Luis M

    2015-01-01

    Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 10(9)/L) after the second weekly rituximab infusion (375 mg/m(2) weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections. PMID:25767732

  5. Early-Onset Neutropenia Induced by Rituximab in a Patient with Lupus Nephritis and Hemolytic Anemia

    PubMed Central

    Arroyo-Ávila, Mariangelí; Fred-Jiménez, Ruth M.; Vilá, Luis M.

    2015-01-01

    Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 109/L) after the second weekly rituximab infusion (375 mg/m2 weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections. PMID:25767732

  6. Remission of proteinuria indicates good prognosis in patients with diffuse proliferative lupus nephritis.

    PubMed

    Koo, H S; Kim, S; Chin, H J

    2016-01-01

    Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy-diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 ± 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow-up period. During a mean follow-up of 157.9 ± 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission. PMID:26159540

  7. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

    PubMed Central

    Tamirou, Farah; D'Cruz, David; Sangle, Shirish; Remy, Philippe; Vasconcelos, Carlos; Fiehn, Christoph; Ayala Guttierez, Maria del Mar; Gilboe, Inge-Magrethe; Tektonidou, Maria; Blockmans, Daniel; Ravelingien, Isabelle; le Guern, Véronique; Depresseux, Geneviève; Guillevin, Loïc; Cervera, Ricard; Houssiau, Frédéric A

    2016-01-01

    Objective To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. Methods In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. Results Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. Conclusions The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome. Trial registration number NCT00204022. PMID:25757867

  8. Lupus Nephritis

    MedlinePlus

    ... Griffin Rodgers, Director of the NIDDK Clinical Trials Current research studies and how you can volunteer Community Outreach and Health Fairs Science-based information and tips for planning an outreach effort or community event For Health Care Professionals Patient and provider resources ...

  9. Lupus Nephritis

    MedlinePlus

    ... a lab for analysis. For the test, a nurse or technician places a strip of chemically treated ... slowing the progression of kidney disease. Many people require two or more medications to control their blood ...

  10. Soluble Fas and the −670 Polymorphism of Fas in Lupus Nephritis

    PubMed Central

    Bollain-y-Goytia, Juan José; Arellano-Rodríguez, Mariela; Torres-Del-Muro, Felipe de Jesús; Daza-Benítez, Leonel; Francisco Muñoz-Valle, José; Avalos-Díaz, Esperanza; Herrera-Esparza, Rafael

    2014-01-01

    This study was performed to clarify the role of soluble Fas (sFas) in lupus nephritis (LN) and establish a potential relationship between LN and the −670 polymorphism of Fas in 67 patients with systemic lupus erythematosus (SLE), including a subset of 24 LN patients with proteinuria. Additionally, a group of 54 healthy subjects (HS) was included. The allelic frequency of the −670 polymorphism of Fas was determined using PCR-RFLP analysis, and sFas levels were assessed by ELISA. Additionally, the WT-1 protein level in urine was measured. The Fas receptor was determined in biopsies by immunohistochemistry (IHC) and in situ hybridization (FISH) and apoptotic features by TUNEL. Results. The −670 Fas polymorphism showed that the G allele was associated with increased SLE susceptibility, with an odds ratio (OR) of 1.86. The sFas was significantly higher in LN patients with the G/G genotype, and this subgroup exhibited correlations between the sFas level and proteinuria and increased urinary WT-1 levels. LN group shows increased expression of Fas and apoptotic features. In conclusion, our results indicate that the G allele of the −670 polymorphism of Fas is associated with genetic susceptibility in SLE patients with elevated levels of sFas in LN with proteinuria. PMID:25505993

  11. Lupus nephritis: An approach to diagnosis and treatment in South Africa.

    PubMed

    Okpechi, I G; Ameh, O I

    2015-12-01

    Lupus nephritis (LN) is a significant cause of morbidity and mortality in patients with systemic lupus erythematosus. Delayed recognition and diagnosis of LN may be a common cause of chronic kidney disease among South Africans. Renal biopsy is the gold standard of diagnosing LN; however, this service is not available in many centres and the use of urinalysis, urine microscopic examination and other serological tests can be useful in identifying patients with proliferative LN. Proliferative types of LN (class III, class IV and mixed class V)comprise the larger proportion of patients with this condition. Patients receiving immunosuppressive therapy need to be monitored closely for side-effects and drug-related toxicities. LN patients with end-stage renal disease (class VI) need to be prepared for renal replacement therapy (dialysis and renal transplantation). In all patients, treatment should include adjunctive therapies such as renin angiotensin aldosterone system blockade, bone protection (with calcium supplements and vitamin D), blood pressure control and chloroquine–all of which help to retard the progression of kidney disease. PMID:26933719

  12. Co-existing autosomal dominant polycystic kidney disease and nephrotic syndrome in a Nigerian patient with lupus nephritis.

    PubMed

    Akinbodewa, A A; Adejumo, O A; Ogunsemoyin, A O; Osasan, S A; Adefolalu, O A

    2016-01-01

    A little over 30 cases on co-existing nephrotic syndrome and autosomal dominant polycystic kidney disease (ADPKD) have been reported from different regions of the world since 1957. We present a case report on co-existence of nephrotic syndrome (secondary to lupus nephritis) with ADPKD in a 24-year-old woman from Nigeria. She was positive for anti-double stranded DNA. Renal histology showed International Society of Nephrology/Renal Pathology Society Class II lupus nephritis. The co-existence of nephrotic syndrome and ADPKD may have been overlooked in Africa in the past. There is a need to screen for nephrotic syndrome in patients with ADPKD among clinicians in the African setting. PMID:27044732

  13. Differential Contribution of IL-4 and STAT6 vs STAT4 to the Development of Lupus Nephritis1

    PubMed Central

    Singh, Ram Raj; Saxena, Vijay; Zang, Song; Li, Lily; Finkelman, Fred D.; Witte, David P.; Jacob, Chaim O.

    2008-01-01

    Mechanisms that initiate lupus nephritis and cause progression to end-stage renal disease remain poorly understood. In this study, we show that lupus-prone New Zealand Mixed 2410 mice that develop a severe glomerulosclerosis and rapidly progressive renal disease overexpress IL-4 in vivo. In these mice, STAT6 deficiency or anti-IL-4 Ab treatment decreases type 2 cytokine responses and ameliorates kidney disease, particularly glomerulosclerosis, despite the presence of high levels of IgG anti-dsDNA Abs. STAT4 deficiency, however, decreases type 1 and increases type 2 cytokine responses, and accelerates nephritis, in the absence of high levels of IgG anti-dsDNA Abs. Thus, STAT6 and IL-4 may selectively contribute to the development of glomerulosclerosis, whereas STAT4 may play a role in autoantibody production. PMID:12707364

  14. Glomerular autoimmune multicomponents of human lupus nephritis in vivo: α-enolase and annexin AI.

    PubMed

    Bruschi, Maurizio; Sinico, Renato Alberto; Moroni, Gabriella; Pratesi, Federico; Migliorini, Paola; Galetti, Maricla; Murtas, Corrado; Tincani, Angela; Madaio, Michael; Radice, Antonella; Franceschini, Franco; Trezzi, Barbara; Bianchi, Laura; Giallongo, Agata; Gatti, Rita; Tardanico, Regina; Scaloni, Andrea; D'Ambrosio, Chiara; Carnevali, Maria Luisa; Messa, Piergiorgio; Ravani, Pietro; Barbano, Giancarlo; Bianco, Beatrice; Bonanni, Alice; Scolari, Francesco; Martini, Alberto; Candiano, Giovanni; Allegri, Landino; Ghiggeri, Gian Marco

    2014-11-01

    Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-α-enolase/low anti-annexin AI IgG2 and patients with low anti-α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum. PMID:24790181

  15. [Renal thrombotic microangiopathy and antiphospholipid syndrome nephropathy in a patient with lupus nephritis].

    PubMed

    Sakamaki, Yusuke; Konishi, Konosuke; Hashiguchi, Akinori; Tomita, Shigeki; Kubota, Eiji; Itoh, Hiroshi; Hayashi, Koichi

    2016-01-01

    The patient was a 48-year-old Japanese woman diagnosed as having systemic lupus erythematosus at the age of 21 years when she presented with fever and an erythematous skin rash on her face and extremities. Prednisolone was initiated at that time. Thirteen days before admission to our hospital, she was referred to us by her family physician. Upon admission, blood tests showed pancytopenia, hypocomplementemia, and renal dysfunction, as well as the presence of lupus anticoagulant. Urinalysis showed abundant proteinuria and heavy microscopic hematuria. After performing a renal biopsy, we initiated immunosuppressive therapy and an anticoagulant. On the 22nd hospital day, microangiopathic hemolytic anemia appeared with the progression of thrombocytopenia and renal failure, and the patient subsequently underwent ten sessions of plasma exchange. After the commencement of the plasma exchange, her general condition improved. Her renal dysfunction, however, continued to progress, and hemodialysis was started on the 36th hospital day. The light microscopy showed severe endo- and extra-capillary proliferative glomerulonephritis with abundant crescents, and massive thrombi in the capillary lumen of the glomeruli. The arterioles contained occlusive hyaline materials. An immunofluorescence study showed granular staining of immunoglobulins and complements along the glomerular capillary wall. An electron microscopy examination revealed the presence of electron-dense deposits in the subepithelial and intramembranous areas of the glomeruli, but subendothelial deposits were absent. For cases with lupus nephritis (LN), immunosuppressive therapy based on corticosteroid remains the mainstay of treatment. However, immunosuppression alone may be insufficient when antiphospholipid antibody syndrome and thrombotic microangiopathy (TMA) are also present, and other treatment modalities including antiplatelet therapy, anticoagulation, and plasma exchange are likely to be necessary, as

  16. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo: α-Enolase and Annexin AI

    PubMed Central

    Bruschi, Maurizio; Sinico, Renato Alberto; Moroni, Gabriella; Pratesi, Federico; Migliorini, Paola; Galetti, Maricla; Murtas, Corrado; Tincani, Angela; Madaio, Michael; Radice, Antonella; Franceschini, Franco; Trezzi, Barbara; Bianchi, Laura; Giallongo, Agata; Gatti, Rita; Tardanico, Regina; Scaloni, Andrea; D’Ambrosio, Chiara; Carnevali, Maria Luisa; Messa, Piergiorgio; Ravani, Pietro; Barbano, Giancarlo; Bianco, Beatrice; Bonanni, Alice; Scolari, Francesco; Martini, Alberto; Candiano, Giovanni; Allegri, Landino

    2014-01-01

    Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti–α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti–α-enolase/low anti-annexin AI IgG2 and patients with low anti–α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti–α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum. PMID:24790181

  17. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens.

    PubMed

    Bruschi, Maurizio; Galetti, Maricla; Sinico, Renato Alberto; Moroni, Gabriella; Bonanni, Alice; Radice, Antonella; Tincani, Angela; Pratesi, Federico; Migliorini, Paola; Murtas, Corrado; Franceschini, Franco; Trezzi, Barbara; Brunini, Francesca; Gatti, Rita; Tardanico, Regina; Barbano, Giancarlo; Piaggio, Giorgio; Messa, Piergiorgio; Ravani, Pietro; Scolari, Francesco; Candiano, Giovanni; Martini, Alberto; Allegri, Landino; Ghiggeri, Gian Marco

    2015-08-01

    Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti-α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti-α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti-α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis. PMID:25398787

  18. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens

    PubMed Central

    Bruschi, Maurizio; Galetti, Maricla; Sinico, Renato Alberto; Moroni, Gabriella; Bonanni, Alice; Radice, Antonella; Tincani, Angela; Pratesi, Federico; Migliorini, Paola; Murtas, Corrado; Franceschini, Franco; Trezzi, Barbara; Brunini, Francesca; Gatti, Rita; Tardanico, Regina; Barbano, Giancarlo; Piaggio, Giorgio; Messa, Piergiorgio; Ravani, Pietro; Scolari, Francesco; Candiano, Giovanni; Martini, Alberto; Allegri, Landino

    2015-01-01

    Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti–α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti–α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti–α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis. PMID:25398787

  19. Evaluating the association of interleukin-10 gene promoter -592 A/C polymorphism with lupus nephritis susceptibility

    PubMed Central

    Abdallah, Emad; Waked, Emam; Abdelwahab, Mahmoud A.

    2015-01-01

    Background Interleukin-10 (IL-10) is an important immunoregulatory cytokine. There are few studies evaluating the association between IL-10 and lupus nephritis (LN). The aim of this study was to evaluate the association of IL-10 gene promoter -592 A/C with LN susceptibility. Methods The study was conducted on 84 patients with systemic lupus erythematosus (SLE). Patients were divided into LN group (Group I, 48 patients) and non-LN group (Group II, 36 patients). The -592 A/C polymorphisms in IL-10 promoter gene were determined by polymerase chain reaction and restriction fragment length polymorphism in both groups. IL-10 was determined by enzyme-linked immunosorbent assay. Frequencies of the genotypes were compared between LN and non-LN patients and among LN patients with different pathologic classes. Results There was a significant increase in serum level of IL-10 (P = 0.001) in Group I compared with Group II and significant positive correlation between serum IL-10 and SLE disease activity index (r = 0.466, P = 0.001) in Group I. There were no significant differences in the distribution of the IL-10 gene promoter -592 A/C genotypes or the allele frequencies between Groups I and II. There was no significant difference between AC/CC and AA genotypes with SLE disease activity index, proteinuria, hematuria, anti-double-stranded DNA, and IL-10 in Group I. There was no significant difference in the distribution of AC and CC genotypes among different pathologic LN classes. Conclusion IL-10 suggested to play a role in pathogenesis and development of LN. However, the promoter -592 A/C of IL-10 gene suggested to be not associated with serum IL-10 levels or LN susceptibility. In addition, it appears that promoter -592 A/C of IL-10 gene not associated with LN activity or the pathologic classes of LN. PMID:27069855

  20. Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy

    PubMed Central

    Sui, Manshu; Han, Jihua; Sun, Lijie; Jia, Xiuzhi; Zhang, Haiyu; Han, Changsong; Jin, Xiaoming; Gao, Fei; Liu, Yanhong; Li, Yang; Cao, Jianbin; Ling, Hong; Zhang, Fengmin; Ren, Huan

    2015-01-01

    Objective To characterize the significance of correlated autoantibodies in systemic lupus erythematosus (SLE) and its complication lupus nephritis (LN) in a large cohort of patients. Methods Clinical data were statistically analyzed in 1699 SLE patients with or without nephritis who were diagnosed and treated during 2002–2013 in the northeast region of China. Reactivity to a list of 16 autoantibodies was detected by the serum test Euroline ANA profile (IgG). Serum titers of the anti-nucleosome autoantibodies were measured by ELISA assays. Kidney biopsies were examined by pathologists. Immune complex deposition was identified by immunohistochemistry stain. Results Simultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos) was prevalent in SLE patients with LN compared to Non-renal SLE patients (41% vs 11%, p< 0.001). Significant correlations were found between any two of the above three anti-nucleosome antibodies in LN patients. In comparison to non-3-pos cohorts, 3-pos patients with LN had significantly higher serum levels of the three antibodies and more active disease; was associated with type IV disease; suffered from more severe renal damages; received more intensive treatment and had worse disease outcome. The serum levels of these three autoantibodies in 3-pos LN patients were significantly decreased when they underwent clinical recovery. Conclusions Simultaneous reactivity to anti-dsDNA, -nucleosome and -histone antibodies by Euroline ANA profile (IgG) may indicate severe nephropathy in patients with SLE. PMID:26465327

  1. Endogenous interleukin (IL)-17A promotes pristane-induced systemic autoimmunity and lupus nephritis induced by pristane.

    PubMed

    Summers, S A; Odobasic, D; Khouri, M B; Steinmetz, O M; Yang, Y; Holdsworth, S R; Kitching, A R

    2014-06-01

    Interleukin (IL)-17A is increased both in serum and in kidney biopsies from patients with lupus nephritis, but direct evidence of pathogenicity is less well established. Administration of pristane to genetically intact mice results in the production of autoantibodies and proliferative glomerulonephritis, resembling human lupus nephritis. These studies sought to define the role of IL-17A in experimental lupus induced by pristane administration. Pristane was administered to wild-type (WT) and IL-17A(-/-) mice. Local and systemic immune responses were assessed after 6 days and 8 weeks, and autoimmunity, glomerular inflammation and renal injury were measured at 7 months. IL-17A production increased significantly 6 days after pristane injection, with innate immune cells, neutrophils (Ly6G(+)) and macrophages (F4/80(+)) being the predominant source of IL-17A. After 8 weeks, while systemic IL-17A was still readily detected in WT mice, the levels of proinflammatory cytokines, interferon (IFN)-γ and tumour necrosis factor (TNF) were diminished in the absence of endogenous IL-17A. Seven months after pristane treatment humoral autoimmunity was diminished in the absence of IL-17A, with decreased levels of immunoglobulin (Ig)G and anti-dsDNA antibodies. Renal inflammation and injury was less in the absence of IL-17A. Compared to WT mice, glomerular IgG, complement deposition, glomerular CD4(+) T cells and intrarenal expression of T helper type 1 (Th1)-associated proinflammatory mediators were decreased in IL-17A(-/-) mice. WT mice developed progressive proteinuria, but functional and histological renal injury was attenuated in the absence of IL-17A. Therefore, IL-17A is required for the full development of autoimmunity and lupus nephritis in experimental SLE, and early in the development of autoimmunity, innate immune cells produce IL-17A. PMID:24528105

  2. RNA sensing by conventional dendritic cells is central to the development of lupus nephritis.

    PubMed

    Celhar, Teja; Hopkins, Richard; Thornhill, Susannah I; De Magalhaes, Raquel; Hwang, Sun-Hee; Lee, Hui-Yin; Yasuga, Hiroko; Jones, Leigh A; Casco, Jose; Lee, Bernett; Thamboo, Thomas P; Zhou, Xin J; Poidinger, Michael; Connolly, John E; Wakeland, Edward K; Fairhurst, Anna-Marie

    2015-11-10

    Glomerulonephritis is a common and debilitating feature of systemic lupus erythematosus (SLE). The precise immune mechanisms that drive the progression from benign autoimmunity to glomerulonephritis are largely unknown. Previous investigations have shown that a moderate increase of the innate Toll-like receptor 7 (TLR7) is sufficient for the development of nephritis. In these systems normalization of B-cell TLR7 expression or temporal depletion of plasmacytoid dendritic cells (pDCs) slow progression; however, the critical cell that is responsible for driving full immunopathology remains unidentified. In this investigation we have shown that conventional DC expression of TLR7 is essential for severe autoimmunity in the Sle1Tg7 model of SLE. We show that a novel expanding CD11b(+) conventional DC subpopulation dominates the infiltrating renal inflammatory milieu, localizing to the glomeruli. Moreover, exposure of human myeloid DCs to IFN-α or Flu increases TLR7 expression, suggesting they may have a role in self-RNA recognition pathways in clinical disease. To our knowledge, this study is the first to highlight the importance of conventional DC-TLR7 expression for kidney pathogenesis in a murine model of SLE. PMID:26512111

  3. Ultrastructural localization of DNA in immune deposits of human lupus nephritis.

    PubMed Central

    Malide, D.; Londoño, I.; Russo, P.; Bendayan, M.

    1993-01-01

    DNA molecules were revealed in the glomerular wall of lupus nephritis patients by applying two specific colloidal gold cytochemical approaches at the electron microscope level: immunocytochemistry using a monoclonal anti-DNA antibody in conjunction with protein A-gold and enzyme-gold cytochemistry using DNAse-gold complexes. Application of both techniques has demonstrated that DNA molecules are preferentially located over the electron-dense deposits found in the glomerular basement membrane and mesangial matrix of SLE patients, as well as over the nuclei. Their distribution within the glomerular wall was correlated with electron-dense immune deposits revealed by anti-light chain antibodies. In normal control kidney, DNA labeling was restricted to the cell nuclei. Several control experiments have demonstrated the high specificity of the results. These data thus suggest a possible role for DNA as an antigenic component in the formation of immune complexes. Images Figure 1 Figure 2 and 3 Figure 4 and 5 Figure 6 Figure 7 PMID:8317553

  4. RNA sensing by conventional dendritic cells is central to the development of lupus nephritis

    PubMed Central

    Celhar, Teja; Hopkins, Richard; Thornhill, Susannah I.; De Magalhaes, Raquel; Hwang, Sun-Hee; Lee, Hui-Yin; Yasuga, Hiroko; Jones, Leigh A.; Casco, Jose; Lee, Bernett; Thamboo, Thomas P.; Zhou, Xin J.; Poidinger, Michael; Connolly, John E.; Wakeland, Edward K.; Fairhurst, Anna-Marie

    2015-01-01

    Glomerulonephritis is a common and debilitating feature of systemic lupus erythematosus (SLE). The precise immune mechanisms that drive the progression from benign autoimmunity to glomerulonephritis are largely unknown. Previous investigations have shown that a moderate increase of the innate Toll-like receptor 7 (TLR7) is sufficient for the development of nephritis. In these systems normalization of B-cell TLR7 expression or temporal depletion of plasmacytoid dendritic cells (pDCs) slow progression; however, the critical cell that is responsible for driving full immunopathology remains unidentified. In this investigation we have shown that conventional DC expression of TLR7 is essential for severe autoimmunity in the Sle1Tg7 model of SLE. We show that a novel expanding CD11b+ conventional DC subpopulation dominates the infiltrating renal inflammatory milieu, localizing to the glomeruli. Moreover, exposure of human myeloid DCs to IFN-α or Flu increases TLR7 expression, suggesting they may have a role in self-RNA recognition pathways in clinical disease. To our knowledge, this study is the first to highlight the importance of conventional DC-TLR7 expression for kidney pathogenesis in a murine model of SLE. PMID:26512111

  5. Intractable membranous lupus nephritis showing selective improvement of subepithelial deposits with tacrolimus therapy: a case report.

    PubMed

    Nonaka, Kanae; Ubara, Yoshifumi; Suwabe, Tatsuya; Takaichi, Kenmei; Oohashi, Kenichi

    2013-08-01

    A 37-year-old female patient was admitted for evaluation of nephrotic proteinuria refractory to prednisolone and other immunosuppressants in 2004. On admission, urinary protein loss was 16 g/d. Anti-ds DNA antibody was positive and hypocomplementemia was detected. Renal biopsy revealed membranous lupus nephritis. Because 5 cyclophosphamide pulse therapies did not have an effect, tacrolimus was started at 3 mg daily. Proteinuria decreased to 4.8 g/d after 5 months and was < 0.1 g/d in 2009, but antids DNA antibody remained positive and hypocomplementemia persisted. Repeat renal biopsy revealed thinning of the glomerular capillary walls and disappearance of subepithelial electron-dense deposits. However, the subendothelial and mesangial deposits were unchanged. In this patient, proteinuria refractory to various immunosuppressants including cyclosporine A improved after administration of tacrolimus, and selective disappearance of subepithelial deposits was seen histologically. This is the first histological evidence that tacrolimus therapy may cause removal of subepithelial deposits, which are separated from the circulation by the glomerular basement membrane. This finding is supported by experimental data that tacrolimus selectively block the binding of FK-binding protein 12 to transient receptor potential-cation channel 6, resulting in normalization of affected podocytes. PMID:22541676

  6. Cardiovascular risk in lupus nephritis: Do renal disease-related and other traditional risk factors play a role?

    PubMed

    Atukorala, Inoshi; Weeratunga, Praveen; Kalubowila, Janaka; Ranasinghe, Hasanthika; Gunawardena, Nalika; Lanerolle, Rushika; Rathnamalala, Nadeeka

    2015-01-01

    This study was performed to evaluate the prevalence of thickened carotid intima media thickness (CIMT) in a Sri Lankan cohort of lupus nephritis (LN) patients and to identify associations between traditional cardiovascular disease (CVD) and LN-related risk factors with increased CIMT. Consecutive patients with biopsy-proven LN were evaluated for conventional CVD risk factors, renal parameters and extent of organ involvement in this cross-sectional study. Current disease activity and damage were assessed by the British Isles Lupus Activity Group (BILAG) score and the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index, respectively. CIMT was assessed by B Mode grey scale ultrasonography. Increased CIMT was defined as CIMT more than the 75th percentile based on cutoffs from the "Carotid Atherosclerosis Progression Study." Forty patients (98% female), with a mean age of 38 years (age range of 20-50) and of South Asian descent, were evaluated. The mean duration of disease of 6.15 years (SD = 4.66). The overall prevalence of cardiovascular events was low and included previous acute coronary syndromes in 7.5%, stable angina in 5%, cerebrovascular accidents in 7.5% and transient ischemic attacks in 2.5% of the patients; 72.5% had hypertension (HTN) [mean blood pressure (BP) 140/80 mm Hg]; 32.5% had dyslipidemias (mean serum cholesterol 5.9; SD = 5.6) and 25% had diabetes (mean blood sugar 103.7; SD = 15.6). Forty percent were obese and 20% were overweight (Asian cutoffs). Increased CIMT (57.5%) and atherosclerotic plaques (15.36%) indicated a high CVD risk in this cohort. Diabetes (P = 0.016), HTN (P = 0.002), dyslipidemia (P = 0.002) and obesity (P = 0.048) were associated with thickened CIMT. The only LN-related risk factor associated with thickened CIMT (P <0.05) was the SLICC/ACR damage index. The independent predictors of thickened CIMT determined by logistic regression analysis were HTN and dyslipidemia. PMID

  7. Targeted IgA Fc receptor I (FcαRI) therapy in the early intervention and treatment of pristane-induced lupus nephritis in mice.

    PubMed

    Liu, C; Kanamaru, Y; Watanabe, T; Tada, N; Horikoshi, S; Suzuki, Y; Liu, Z; Tomino, Y

    2015-09-01

    The Fc receptor I for IgA (FcαRI) down-regulates humoral immune responses and modulates the risk of autoimmunity. This study aimed to investigate whether FcαRI targeting can affect progression of pristine-induced lupus nephritis. In the first experiment (early intervention), four groups of animals were evaluated: untreated FcαRI/FcRγ transgenic (Tg) mice and Tg mice administered control antibody (Ctr Fab), saline and anti-FcαRI Fab [macrophage inflammatory protein (MIP)-8a], respectively, three times a week for 29 weeks, after being injected once intraperitoneally with 0·5 ml pristane. In the second experiment, antibody injection started after the onset of nephritis and was carried out for 2 months, with similar groups as described above. MIP-8a improved proteinuria, decreased the amounts of glomerular injury markers, serum interleukin (IL)-6, IL-1 and monocyte chemoattractant protein (MCP)-1, and F4/80 macrophages in the interstitium and glomeruli, in both experiments. When MIP-8a was used as early intervention, a decrease in mouse serum anti-nuclear antibody (ANA) titres and reduced deposition of immunoglobulins in glomeruli were observed. This effect was associated with reduced serum titres of immunoglobulin (Ig)G2a but not IgG1, IgG2b and IgG3. Furthermore, pathological analysis showed lower glomerular activity index and less fibronectin in MIP-8a treated mice. This study suggests that FcαRI targeting could halt disease progression and lupus activation by selective inhibition of cytokine production, leucocyte recruitment and renal inflammation. Our findings provide a basis for the use of FcαRI as a molecular target for the treatment of lupus. PMID:25907714

  8. Aspergillus-Associated Cerebral Aneurysm Successfully Treated by Endovascular and Surgical Intervention with Voriconazole in Lupus Nephritis Patient

    PubMed Central

    Kim, Yong Chul; Lee, Hajeong; Ryu, Han Hee; Beom, Seung Hoon; Yang, Yaewon; Kim, Suhnggwon

    2012-01-01

    During the last five decades, long-term therapy with immunosuppressive agents such as pulse cyclophosphamide in conjunction with high-dose corticosteroids has enhanced both patient survival and renal survival in patients with diffuse proliferative lupus nephritis. Nevertheless, severe side effects such as infectious complications remain the main cause of morbidity and mortality. Central nervous system aspergillosis is uncommon but life-threatening in lupus patients. In this single-patient case study, carotid aneurysm with sphenoidal sinusitis was suspected when severe epistaxis occurred during cyclophosphamide pulse therapy. With anti-fungal therapy, a graft stent was successfully deployed to the aneurysm and specimens of sphenoidal mucosa showed typical hyphae, indicating aspergillosis. Three months after stopping voriconazole treatment, two cerebral aneurysms that were revealed on MR images were successfully removed by aneurysmal clipping. The patient remained alive at one-year follow-up with lupus nephritis in remission. The rarity and high mortality of aspergillus-related fungal aneurysms have led to most cases being recognized postmortem. However, such aneurysms must be diagnosed early to prevent fatal complications by performing appropriate management such as surgical procedure or endovascular intervention. PMID:22379345

  9. Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus

    PubMed Central

    2011-01-01

    Introduction Inherited deficiencies of several complement components strongly predispose to systemic lupus erythematosus (SLE) while deficiencies of complement inhibitors are found in kidney diseases such as atypical hemolytic uremic syndrome (aHUS). Methods The exons of complement inhibitor genes CD46 and CFH (factor H) were fully sequenced using the Sanger method in SLE patients with nephritis originating from two cohorts from southern and mid Sweden (n = 196). All identified mutations and polymorphisms were then analyzed in SLE patients without nephritis (n = 326) and in healthy controls (n = 523). Results We found nonsynonymous, heterozygous mutations in CFH in 6.1% patients with nephritis, in comparison with 4.0% and 5.4% in patients without nephritis and controls, respectively. No associations of SLE or nephritis with common variants in CFH (V62I/Y402H/E936D) were found. Furthermore, we found two nonsynonymous heterozygous mutations in CD46 in SLE patients but not in controls. The A353V polymorphism, known to affect function of CD46, was found in 6.6% of nephritis patients versus 4.9% and 6.1% of the non-nephritis SLE patients and controls. The presence of mutations in CD46 and CFH did not predispose to SLE or nephritis but was associated with earlier onset of nephritis. Furthermore, we found weak indications that there is one protective and one risk haplotype predisposing to nephritis composed of several polymorphisms in noncoding regions of CD46, which were previously implicated in aHUS. Conclusions SLE nephritis is not associated with frequent mutations in CFH and CD46 as found in aHUS but these may be modifying factors causing earlier onset of nephritis. PMID:22171659

  10. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide

    PubMed Central

    Verstuyft, Céline; Costedoat-Chalumeau, Nathalie; Hummel, Aurélie; Le Guern, Véronique; Sacré, Karim; Meyer, Olivier; Daugas, Eric; Goujard, Cécile; Sultan, Audrey; Lobbedez, Thierry; Galicier, Lionel; Pourrat, Jacques; Le Hello, Claire; Godin, Michel; Morello, Rémy; Lambert, Marc; Hachulla, Eric; Vanhille, Philippe; Queffeulou, Guillaume; Potier, Jacky; Dion, Jean-Jacques; Bataille, Pierre; Chauveau, Dominique; Moulis, Guillaume; Farge-Bancel, Dominique; Duhaut, Pierre; Saint-Marcoux, Bernadette; Deroux, Alban; Manuzak, Jennifer; Francès, Camille; Aumaitre, Olivier; Bezanahary, Holy; Becquemont, Laurent; Bienvenu, Boris

    2016-01-01

    Objective To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. Results Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02–24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064–10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. Conclusion This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients. PMID:27002825

  11. Characterising the immune profile of the kidney biopsy at lupus nephritis flare differentiates early treatment responders from non-responders

    PubMed Central

    Parikh, Samir V; Malvar, Ana; Song, Huijuan; Alberton, Valeria; Lococo, Bruno; Vance, Jay; Zhang, Jianying; Yu, Lianbo; Rovin, Brad H

    2015-01-01

    Introduction The kidney biopsy is used to diagnose and guide initial therapy in patients with lupus nephritis (LN). Kidney histology does not correlate well with clinical measurements of kidney injury or predict how patients will respond to standard-of-care immunosuppression. We postulated that the gene expression profile of kidney tissue at the time of biopsy may differentiate patients who will from those who will not respond to treatment. Methods The expression of 511 immune-response genes was measured in kidney biopsies from 19 patients with proliferative LN and 4 normal controls. RNA was extracted from formalin-fixed, paraffin-embedded kidney biopsies done at flare. After induction therapy, 5 patients achieved a complete clinical response (CR), 10 had a partial response (PR) and 4 patients were non-responders (NRs). Transcript expression was compared with normal controls and between renal response groups. Results A principal component analysis showed that intrarenal transcript expression from normal kidney, CR biopsies and NR biopsies segregated from each other. The top genes responsible for CR clustering included several interferon pathway genes (STAT1, IRF1, IRF7, MX1, STAT2, JAK2), while complement genes (C1R, C1QB, C6, C9, C5, MASP2) were mainly responsible for NR clustering. Overall, 35 genes were uniquely expressed in NR compared with CR. Pathway analysis revealed that interferon signalling and complement activation pathways were upregulated in both groups, while BAFF, APRIL, nuclear factor-κB and interleukin-6 signalling were increased in CR but suppressed in NR. Conclusions These data suggest that molecular profiling of the kidney biopsy at LN flare may be useful in predicting treatment response to induction therapy. PMID:26629350

  12. Long-term Outcome of Lupus Nephritis Class II in Argentine Patients

    PubMed Central

    Collado, Maria Victoria; Dorado, Enrique; Rausch, Silvia; Gomez, Graciela; Khoury, Marina; Zazzetti, Federico; Gargiulo, María; Suarez, Lorena; Chaparro, Rafael; Paira, Sergio; Galvan, Laura; Juarez, Vicente; Pisoni, Cecilia; Garcia, Mercedes; Martinez, Liliana; Alvarez, Analia; Alvarez, Clarisa; Barreira, Juan; Sarano, Judith

    2016-01-01

    Background There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. Methods A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. Results Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133). In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). Conclusions This

  13. Characterization of Patients With Lupus Nephritis Included in a Large Cohort From the Spanish Society of Rheumatology Registry of Patients With Systemic Lupus Erythematosus (RELESSER)

    PubMed Central

    Galindo-Izquierdo, María; Rodriguez-Almaraz, Esther; Pego-Reigosa, José M.; López-Longo, Francisco J.; Calvo-Alén, Jaime; Olivé, Alejandro; Fernández-Nebro, Antonio; Martinez-Taboada, Víctor; Vela-Casasempere, Paloma; Freire, Mercedes; Narváez, Francisco J.; Rosas, José; Ibáñez-Barceló, Mónica; Uriarte, Esther; Tomero, Eva; Zea, Antonio; Horcada, Loreto; Torrente, Vicenç; Castellvi, Iván; Calvet, Joan; Menor-Almagro, Raúl; Zamorano, María A. Aguirre; Raya, Enrique; Díez-Álvarez, Elvira; Vázquez-Rodríguez, Tomás; García de la Peña, Paloma; Movasat, Atusa; Andreu, José L.; Richi, Patricia; Marras, Carlos; Montilla-Morales, Carlos; Hernández-Cruz, Blanca; Marenco de la Fuente, José L.; Gantes, María; Úcar, Eduardo; Alegre-Sancho, Juan J.; Manero, Javier; Ibáñez-Ruán, Jesús; Rodríguez-Gómez, Manuel; Quevedo, Víctor; Hernández-Beriaín, José; Silva-Fernández, Lucía; Alonso, Fernando; Pérez, Sabina; Rúa-Figueroa, Iñigo

    2016-01-01

    Abstract The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ± 12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 [1.81–3.22], P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P

  14. [Successful bosentan therapy in a case of pulmonary arterial hypertention developed during immunosuppressive therapy for lupus nephritis].

    PubMed

    Ueda, Yo; Takahashi, Yuko; Yamashita, Hiroyuki; Kaneko, Hiroshi; Mimori, Akio

    2011-01-01

    We report a 43-year-old female who developed pulmonary arterial hypertension (PAH) during intensive immunosuppressive therapy for systematic lupus erythematosus (SLE). She was diagnosed as SLE at the age of 32 years based on serological and hematological abnormalities, oral ulcers, and facial erythema. She experienced frequent flare-ups of disseminated discoid lupus between the ages of 33 and 36 years and developed immune thrombocytopenia at the age of 39 years. In 2007 when she was 43 years old, she developed lupus nephritis (LN) with elevated serum anti-double stranded DNA antibodies and urine protein of less than 1 g/day. Combination therapy for the LN with 35 mg/day prednisolone and intravenous cyclophosphamide (IVCY) led to renal remission. After the seventh monthly session of IVCY, she developed dyspnea on exertion. PAH was diagnosed based on enlarged main pulmonary arteries on the chest x-ray, right ventricular outflow and a peak tricuspid regurgitant pressure gradient exceeding 45 mmHg on echocardiography, an elevated plasma brain natriuretic peptide (BNP) level of 260 pg/ml, the exclusion of pulmonary thromboembolism, and no lung fibrosis. The PAH was treated successfully with bosentan. At present the tricuspid regurgitation has disappeared, and the plasma BNP level has normalized. PMID:21628852

  15. Role of MYH9 and APOL1 in African and non-African populations with Lupus Nephritis

    PubMed Central

    Lin, Chee Paul; Adrianto, Indra; Lessard, Christopher J.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Guthridge, Joel M.; Freedman, Barry I.; Anaya, Juan-Manuel; Alarcón-Riquelme, Marta E.; Pons-Estel, Bernardo A.; Martin, Javier; Glenn, Stuart; Adler, Adam; Bae, Sang-Cheol; Park, So-Yeon; Bang, So-Young; Song, Yeong-Wook; Boackle, Susan A.; Brown, Elizabeth E.; Edberg, Jeffrey C.; Alarcón, Graciela S.; Petri, Michelle A.; Criswell, Lindsey A.; Ramsey-Goldman, Rosalind; Reveille, John D.; Vila, Luis M.; Gilkeson, Gary S.; Kamen, Diane L.; Ziegler, Julie; Jacob, Chaim O.; Rasmussen, Astrid; James, Judith A.; Kimberly, Robert P.; Merrill, Joan T.; Niewold, Timothy B.; Scofield, R. Hal; Stevens, Anne M.; Tsao, Betty P.; Vyse, Timothy J.; Langefeld, Carl D.; Moser, Kathy L.; Harley, John B.; Gaffney, Patrick M.; Montgomery, Courtney G.

    2012-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected p-value of p < 2.03 × 10−3 were observed between LN and MYH9 in EAs (N=4620), with the most pronounced association at rs2157257 (p = 4.7 × 10−4; odds ratio [OR]=1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, p = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population and presents novel insight into the potential role of MYH9 in LN in EAs. PMID:22189356

  16. Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.

    PubMed

    Lin, C P; Adrianto, I; Lessard, C J; Kelly, J A; Kaufman, K M; Guthridge, J M; Freedman, B I; Anaya, J-M; Alarcón-Riquelme, M E; Pons-Estel, B A; Martin, J; Glenn, S; Adler, A; Bae, S-C; Park, S-Y; Bang, S-Y; Song, Y-W; Boackle, S A; Brown, E E; Edberg, J C; Alarcón, G S; Petri, M A; Criswell, L A; Ramsey-Goldman, R; Reveille, J D; Vila, L M; Gilkeson, G S; Kamen, D L; Ziegler, J; Jacob, C O; Rasmussen, A; James, J A; Kimberly, R P; Merrill, J T; Niewold, T B; Scofield, R H; Stevens, A M; Tsao, B P; Vyse, T J; Langefeld, C D; Moser, K L; Harley, J B; Gaffney, P M; Montgomery, C G

    2012-04-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs. PMID:22189356

  17. Postpartum dilated cardiomyopathy in a patient with systemic lupus erythematosus, nephritis and lupus anticoagulant: a diagnostic dilemma

    PubMed Central

    Hall, Daniel; New, David; Kelly, Teresa

    2011-01-01

    A 32-year-old Caucasian woman presented with shortness of breath four weeks postpartum. She was known to suffer from systemic lupus erythematosus with cutaneous, joint and minor renal involvement. During pregnancy, the patient had developed nephrotic syndrome for which she was managed with prophylactic anticoagulation and corticosteroid therapy. A leg deep vein thrombosis had arisen following caesarean section following antepartum haemorrhage. Examination revealed a heart murmur, and pulmonary signs. Computed tomography pulmonary angiogram showed cardiomegaly and bilateral pleural effusions but no pulmonary embolus. Echocardiogram demonstrated dilated cardiomyopathy. An initial diagnosis of peripartum cardiomyopathy was considered, with lupus myocarditis and coronary in situ thrombosis among the differential diagnoses.

  18. Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis.

    PubMed

    Devarapu, Satish Kumar; Kumar Vr, Santhosh; Rupanagudi, Khader Valli; Kulkarni, Onkar P; Eulberg, Dirk; Klussmann, Sven; Anders, Hans-Joachim

    2016-08-01

    Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to the onset and progression of proliferative lupus nephritis yet through different mechanisms. We hypothesized that dual antagonism could be as potent on lupus nephritis as the unselective immunosuppressant cyclophosphamide (CYC). We estimated serum levels of CCL2 and CXCL12 in patients with SLE (n=99) and compared the results with healthy individuals (n=21). In order to prove our hypothesis we used l-enantiomeric RNA Spiegelmer® chemokine antagonists, i.e. the CCL2-specific mNOX-E36 and the CXCL12-specific NOX-A12 to treat female MRL/lpr mice from week 12 to 20 of age with either anti-CXCL12 or anti-CCL2 alone or both. SLE patients showed elevated serum levels of CCL2 but not of CXCL12. Female MRL/lpr mice treated with dual blockade showed significantly more effective than either monotherapy in preventing proteinuria, immune complex glomerulonephritis, and renal excretory failure and the results are at par with CYC treatment. Dual blockade reduced leukocyte counts and renal IL-6, IL-12p40, CCL-5, CCL-2 and CCR-2 mRNA expression. Dual blockade of CCL2 and CXCL12 can be as potent as CYC to suppress the progression of proliferative lupus nephritis probably because the respective chemokine targets mediate different disease pathomechanisms, i.e. systemic autoimmunity and peripheral tissue inflammation. PMID:27392463

  19. Deletion of receptor for advanced glycation end products exacerbates lymphoproliferative syndrome and lupus nephritis in B6-MRL Fas lpr/j mice.

    PubMed

    Goury, Antoine; Meghraoui-Kheddar, Aïda; Belmokhtar, Karim; Vuiblet, Vincent; Ortillon, Jeremy; Jaisson, Stéphane; Devy, Jerôme; Le Naour, Richard; Tabary, Thierry; Cohen, Jacques H M; Schmidt, Ann-Marie; Rieu, Philippe; Touré, Fatouma

    2015-04-15

    The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that interacts with advanced glycation end products, but also with C3a, CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder associated with the accumulation of RAGE ligands. We generated mice invalidated for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of RAGE in the pathogenesis of systemic lupus erythematosus. We compared the phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j littermates. Lymphoproliferative syndrome, production of anti-dsDNA Abs, lupus nephritis, and accumulation of CD3(+)B220(+)CD4(-)CD8(-) autoreactive T cells (in the peripheral blood and the spleen) were significantly increased in B6-MRL Fas lpr/j RAGE(-/-) mice compared with B6-MRL Fas lpr/j mice (respectively p < 0.005, p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells from B6-MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies of annexin V expression revealed that autoreactive T cells in the spleen of B6-MRL Fas lpr/j-RAGE(-/-) mice exhibited a delay in apoptosis and expressed significantly less activated caspase 3 (39.5 ± 4.3%) than T cells in B6-MRL Fas lpr/j mice (65.5 ± 5.2%) or wild-type mice (75.3 ± 2.64%) (p = 0.02). We conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the accumulation of autoreactive CD3(+)B220(+)CD4(-)CD8(-) T cells, therefore exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor Fas/CD95 is dysfunctional. PMID:25762779

  20. Single-nucleotide polymorphisms in the PLA2R1 gene are associated with systemic lupus erythematosus and lupus nephritis in a Chinese Han population.

    PubMed

    Li, Yuan; Zhou, Aihong; Lv, Guanting; Li, Ping; Chen, Si; Li, Jing; Wen, Xiaoting; Wu, Ziyan; Zhang, Shulan; Wang, Jibo; Zhang, Fengchun; Li, Yongzhe

    2016-02-01

    Several novel susceptibility genes for systemic lupus erythematosus (SLE) and other nephropathy have been identified in recent genome-wide association studies. Membranous nephropathy is the most common diagnosis in adults with the nephrotic syndrome, and both idiopathic membranous nephropathy (IMN) and lupus nephritis (LN) are autoimmune diseases of the kidney; they may share common disease mechanisms that overlap with genetic susceptibility. Therefore, we sought to identify genetic variants associated with IMN in SLE/LN. The PLA2R1 single-nucleotide polymorphisms rs4664308, rs3828323, rs3792189, and rs3792192 were genotyped in a cohort of 1247 SLE patients and 1174 healthy controls, using the Sequenom MassArray system method. PLA2R1 displayed a nominally significantly genetic association with SLE [for rs4664308, P = 0.02, odds ratio (OR) 1.16, 95 % confidence interval (CI) 1.02-1.31; for rs3792192, P = 7.9 × 10(-3), OR 1.18, 95 % CI 1.05-1.34] and LN (for rs4664308, P = 0.04). The frequencies of genotypes of rs3792189 and rs3828323 were significantly different between the SLE patients and controls (all P < 0.05), and the haplotype (AA) formed by rs3792189 and rs3792192 was associated with SLE (P = 0.019). This was the first study to reveal that PLA2R1 polymorphisms were associated with SLE/LN patients, indicating that PLA2R1 might be a susceptibility gene for SLE/LN in a Chinese Han population. PMID:26645973

  1. Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis.

    PubMed

    Seret, Guillaume; Cañas, Felipe; Pougnet-Di Costanzo, Laurence; Hanrotel-Saliou, Catherine; Jousse-Joulin, Sandrine; Le Meur, Yannick; Saraux, Alain; Valeri, Antoine; Putterman, Chaim; Youinou, Pierre; Rojas-Villarraga, Adriana; Anaya, Juan-Manuel; Renaudineau, Yves

    2015-07-01

    Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research. PMID:26071203

  2. [Lupus nephritis associated with common variable immunodeficiency: favourable outcome with intravenous immunoglobulin treatment].

    PubMed

    Geneviève, M; Bonnet, F; Michaux, C; Geffroy, C-E; Vandenhende, M-A; Combe, C; Morlat, P

    2012-06-01

    We report a 24-year-old woman who presented with a nephrotic syndrome as the revealing manifestation of systemic lupus erythematosus (SLE) and an associated hypogammaglobulinemia related to a common variable immunodeficiency (CVID). Outcome of SLE was favourable with intravenous immunoglobulin treatment solely. Relationships between SLE and CVID are discussed. PMID:22560369

  3. Cost-Utility Analysis of Mycophenolate Mofetil versus Azathioprine Based Regimens for Maintenance Therapy of Proliferative Lupus Nephritis

    PubMed Central

    Nee, Robert; Rivera, Ian; Little, Dustin J.; Yuan, Christina M.; Abbott, Kevin C.

    2015-01-01

    Background/Aims. We aimed to examine the cost-effectiveness of mycophenolate mofetil (MMF) and azathioprine (AZA) as maintenance therapy for patients with Class III and Class IV lupus nephritis (LN), from a United States (US) perspective. Methods. Using a Markov model, we conducted a cost-utility analysis from a societal perspective over a lifetime horizon. The modeled population comprised patients with proliferative LN who received maintenance therapy with MMF (2 gm/day) versus AZA (150 mg/day) for 3 years. Risk estimates of clinical events were based on a Cochrane meta-analysis while costs and utilities were retrieved from other published sources. Outcome measures included costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratios (ICER), and net monetary benefit. Results. The base-case model showed that, compared with AZA strategy, the ICER for MMF was $2,630,592/QALY at 3 years. Over the patients' lifetime, however, the ICER of MMF compared to AZA was $6,454/QALY. Overall, the ICER results from various sensitivity and subgroup analyses did not alter the conclusions of the model simulation. Conclusions. In the short term, an AZA-based regimen confers greater value than MMF for the maintenance therapy of proliferative LN. From a lifelong perspective, however, MMF is cost-effective compared to AZA. PMID:26600951

  4. Cost-Utility Analysis of Mycophenolate Mofetil versus Azathioprine Based Regimens for Maintenance Therapy of Proliferative Lupus Nephritis.

    PubMed

    Nee, Robert; Rivera, Ian; Little, Dustin J; Yuan, Christina M; Abbott, Kevin C

    2015-01-01

    Background/Aims. We aimed to examine the cost-effectiveness of mycophenolate mofetil (MMF) and azathioprine (AZA) as maintenance therapy for patients with Class III and Class IV lupus nephritis (LN), from a United States (US) perspective. Methods. Using a Markov model, we conducted a cost-utility analysis from a societal perspective over a lifetime horizon. The modeled population comprised patients with proliferative LN who received maintenance therapy with MMF (2 gm/day) versus AZA (150 mg/day) for 3 years. Risk estimates of clinical events were based on a Cochrane meta-analysis while costs and utilities were retrieved from other published sources. Outcome measures included costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratios (ICER), and net monetary benefit. Results. The base-case model showed that, compared with AZA strategy, the ICER for MMF was $2,630,592/QALY at 3 years. Over the patients' lifetime, however, the ICER of MMF compared to AZA was $6,454/QALY. Overall, the ICER results from various sensitivity and subgroup analyses did not alter the conclusions of the model simulation. Conclusions. In the short term, an AZA-based regimen confers greater value than MMF for the maintenance therapy of proliferative LN. From a lifelong perspective, however, MMF is cost-effective compared to AZA. PMID:26600951

  5. A Protocol for the Pharmacokinetics of Enteric Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN): an open-label, randomised controlled trial

    PubMed Central

    Ranganathan, Dwarakanathan; John, George T; Healy, Helen; Roberts, Matthew J; Fassett, Robert G; Lipman, Jeffrey; Kubler, Paul; Ungerer, Jacobus; McWhinney, Brett C; Lim, Aaron; Purvey, Megan; Reyaldeen, Reza; Roberts, Jason A

    2013-01-01

    Introduction Mycophenolate sodium, an enteric-coated tablet (EC-MPS), is as effective and safe as mycophenolate mofetil (MMF) in preventing transplant rejection. EC-MPS and MMF improve the outcome of severe lupus nephritis (LN) and have fewer side effects than pulsed intravenous cyclophosphamide. Blood concentrations of mycophenolic acid (MPA), the active metabolite of EC-MPS, vary between participants despite fixed dosing. Interpatient variability has been studied in transplantation, but not well documented in LN. The relationship between MPA concentration and its clinical effect on LN has not been described. Methods and analysis This is a prospective, open-label, randomised controlled trial. –32 participants with LN who meet the inclusion and exclusion criteria will be randomised into two groups: one receiving a fixed dose of EC-MPS and the second, a dosing regimen that is titrated with therapeutic drug monitoring. Included participants will have blood sampled over a period of 8–12 h on three different occasions. Pharmacokinetic parameters will be calculated using non-compartmental methods. Ethics and dissemination The Human Research and Ethics Committee of the Royal Brisbane Women's Hospital have approved this study. The study is registered with Australian and New Zealand Clinical Trials Registry—ACTRN12611000798965 We planned to present the de-identified information at conferences and publish the results in medical journals. Trial Registration ACTRN12611000798965 PMID:23929919

  6. A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial

    PubMed Central

    Tamirou, Farah; Lauwerys, Bernard R; Dall'Era, Maria; Mackay, Meggan; Rovin, Brad; Cervera, Ricard; Houssiau, Frédéric A

    2015-01-01

    Background Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts. Trial registration number: NCT00204022. PMID:26629352

  7. Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

    PubMed

    Tedeschi, Sara K; Guan, Hongshu; Fine, Alexander; Costenbader, Karen H; Bermas, Bonnie

    2016-07-01

    Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women's Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12-20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0-12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3-11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0-34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy. PMID:27166627

  8. Next generation sequencing and functional analysis of patient urine renal progenitor-derived podocytes to unravel the diagnosis underlying refractory lupus nephritis.

    PubMed

    Romagnani, Paola; Giglio, Sabrina; Angelotti, Maria Lucia; Provenzano, Aldesia; Becherucci, Francesca; Mazzinghi, Benedetta; Müller, Susanna; Amann, Kerstin; Weidenbusch, Marc; Romoli, Simone; Lazzeri, Elena; Anders, Hans-Joachim

    2016-09-01

    Often the cause of refractory lupus nephritis (RLN) remains unclear. We performed next-generation sequencing for podocyte genes in an RLN patient and identified compound heterozygosity for APOL1 risk alleles G1 and G2 and a novel homozygous c.[1049C>T]+[1049C>T] NPHS1 gene variant of unknown significance. To test for causality renal progenitor cells isolated from urine of this patient were differentiated into podocytes in vitro. Podocytes revealed aberrant nephrin trafficking, cytoskeletal structure and lysosomal leakage, and increased detachment as compared with podocytes isolated from controls. Thus, lupus podocytopathy can be confirmed as a cause of RLN by functional genetics on patient-derived podocytes. PMID:27325253

  9. Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis

    SciTech Connect

    Schmiedeke, T.M.; Stoeckl, F.W.W.; Weber, R.; Sugisaki, Y.; Batsford, S.R.; Vogt, A.

    1989-06-01

    An effort has been made to integrate insights on charge-based interactions in immune complex glomerulonephritis with nuclear antigen involvement in lupus nephritis. Attention was focussed on the histones, a group of highly cationic nuclear constituents, which could be expected to bind to fixed anionic sites present in the glomerular basement membrane (GBM). We demonstrated that all histone subfractions, prepared according to Johns, have a high affinity for GBM and the basement membrane of peritubular capillaries. Tissue uptake of /sup 125/I-labeled histones was measured by injecting 200 micrograms of each fraction into the left kidney via the aorta and measuring organ uptake after 15 min. In glomeruli isolated from the left kidneys, the following quantities of histones were found: f1, 13 micrograms; f2a (f2al + f2a2), 17 micrograms; f2b, 17 micrograms; and f3, 32 micrograms. Kinetic studies of glomerular binding showed that f1 disappeared much more rapidly than f2a. The high affinity of histones (pI between 10.5 and 11.0; mol wt 10,000-22,000) for the GBM correlates well with their ability to form aggregates (mol wt greater than 100,000) for comparison lysozyme (pI 11, mol wt 14,000), which does not aggregate spontaneously bound poorly (0.4 micrograms in isolated glomeruli). The quantity of histones and lysozyme found in the isolated glomeruli paralleled their in vitro affinity for a Heparin-Sepharose column (gradient elution studies). This gel matrix contains the sulfated, highly anionic polysaccharide heparin, which is similar to the negatively charged heparan sulfate present in the GBM. Lysozyme eluted with 0.15 M NaCl, f1 with 1 M NaCl, and f2a, f2b, and f3 could not be fully desorbed even with 2 M NaCl; 6 M guanidine-HCl was necessary.

  10. Dissection of Genetic Mechanisms Governing the Expression of Serum Retroviral gp70 Implicated in Murine Lupus Nephritis1

    PubMed Central

    Baudino, Lucie; Yoshinobu, Kumiko; Morito, Naoki; Kikuchi, Shuichi; Fossati-Jimack, Liliane; Morley, Bernard J.; Vyse, Timothy J.; Hirose, Sachiko; Jørgensen, Trine N.; Tucker, Rebecca M.; Roark, Christina L.; Kotzin, Brian L.; Evans, Leonard H.; Izui, Shozo

    2008-01-01

    The endogenous retroviral envelope glycoprotein, gp70, implicated in murine lupus nephritis is secreted by hepatocytes as an acute phase protein, and has been believed to be a product of an endogenous xenotropic virus, NZB-X1. However, since endogenous polytropic (PT) and modified polytropic (mPT) viruses encode gp70s that are closely related to xenotropic gp70, these viruses can be additional sources of serum gp70. To better understand the genetic basis of the expression of serum gp70, we analyzed the abundance of xenotropic, PT or mPT gp70 RNAs in livers and the genomic composition of corresponding proviruses in various strains of mice, including two different Sgp (serum gp70 production) congenic mice. Our results demonstrated that the expression of different viral gp70 RNAs was remarkable heterogeneous among various mouse strains and that the level of serum gp70 production was regulated by multiple structural and regulatory genes. In addition, a significant contribution of PT and mPT gp70s to serum gp70 was revealed by the detection of PT and mPT, but not xenotropic transcripts in 129 mice and by a closer correlation of serum levels of gp70 with the abundance of PT and mPT gp70 RNAs than with that of xenotropic gp70 RNA in Sgp3 congenic mice. Furthermore, the injection of lipopolysaccharides selectively up-regulated the expression of xenotropic and mPT gp70 RNAs, but not PT gp70 RNA. Our data indicate that the genetic origin of serum gp70 is more heterogeneous than previously believed, and that distinct retroviral gp70s are differentially regulated in physiological vs. inflammatory conditions. PMID:18684976

  11. T-cell receptor Vbeta gene expression in experimental lupus nephritis.

    PubMed Central

    Sutmuller, M; Baelde, H J; Ouellette, S; De Heer, E; Bruijn, J A

    1998-01-01

    A limited T-cell receptor (TCR) Vbeta repertoire employed by autoreactive T cells may be related to the development and course of autoimmune diseases. Vbeta repertoire skewing has been observed not only in man, but also in animal models of several human autoimmune diseases, such as MRL-lpr mice, which spontaneously develop a systemic lupus erythematosus (SLE)-like disease. Murine chronic graft-versus-host disease (GVHD) is an inducible model for SLE, involving direct interaction between donor T cells and recipient B cells. It is not known whether Vbeta-specific T-cell subsets are pathogenically involved in this model. Retroviral superantigens such as Mls-1 are known to have a profound impact on the TCR Vbeta repertoire in mice. Restriction of the peripheral TCR repertoire may result from intrathymic expression of Mls-1, which causes deletion of T cells expressing Vbeta6, -7, -8.1, or -9. Mls-1 incompatibility between donor and recipient can be used to determine the involvement of these TCR Vbeta families in GVHD. In the present study we induced GVHD in several strain combinations to investigate TCR Vbeta gene expression during GVHD, and the effect of Mls-1 incompatibility on the TCR Vbeta repertoire. TCR Vbeta gene expression was determined using an RNase protection assay. Our results indicate that T cells expressing the Vbeta2 or Vbeta16 chain play an important pathogenetic role, while T cells bearing the Vbeta1 or Vbeta6 chain may be related to self-limitation of the lupus-like disease in this model. Images Figure 1 Figure 4 PMID:9767452

  12. Sgp3 and Sgp4 Control Expression of Distinct and Restricted Sets of Xenotropic Retroviruses Encoding Serum gp70 Implicated in Murine Lupus Nephritis

    PubMed Central

    Kihara, Maso; Leroy, Valérie; Baudino, Lucie; Evans, Leonard H.; Izui, Shozo

    2011-01-01

    The envelope glycoprotein gp70 of endogenous retroviruses implicated in murine lupus nephritis is secreted by hepatocytes and its expression is controlled by Sgp3 (serum gp70 production 3) and Sgp4 loci derived from lupusprone mice. Among three different endogenous retroviruses (ecotropic, xenotropic and polytropic), xenotropic viruses are considered to be the major source of serum gp70. Although the abundance of xenotropic viral gp70 RNA in livers was up-regulated by the presence of these two Sgp loci, it has not yet been clear whether Sgp3 and Sgp4 regulate the expression of a fraction or multiple xenotropic viruses present in mouse genome. To address this question, we determined the genetic origin of xenotropic viral sequences expressed in wildtype and two different Sgp congenic C57BL/6 mice. Among 14 xenotropic proviruses present in the C57BL/6 genome, only two proviruses (Xmv10 and Xmv14) were actively transcribed in wild-type C57BL/6 mice. In contrast, Sgp3 enhanced the transcription of Xmv10 and induced the transcription of three additional xenotropic viruses (Xmv15, Xmv17 and Xmv18), while Sgp4 induced the expression of a different xenotropic virus (Xmv13). Notably, stimulation of TLR7 in Sgp3 congenic C57BL/6 mice led to a highly enhanced expression of potentially replication-competent Xmv18. These results indicated that Sgp3 and Sgp4 independently regulated the transcription of distinct and restricted sets of xenotropic viruses in trans, thereby promoting the production of nephritogenic gp70 autoantigens. Furthermore, the induced expression of potentially replication-competent xenotropic viruses by Sgp3 may contribute to the development of autoimmune responses against gp70 through the activation of TLR7. PMID:21982749

  13. Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up

    PubMed Central

    Okada, Kenya; Sudo, Yohei; Itoh, Hiromichi; Yoshida, Hisao; Kuroda, Tatsuhiko

    2014-01-01

    Objective: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Methods: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Results: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7%) of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%). No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. Conclusion: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy. PMID:26770729

  14. Lupus

    MedlinePlus

    What is lupus? Lupus is an autoimmune disease. This means that your immune system attacks healthy cells and tissues by mistake. This can ... vessels, and brain. There are several kinds of lupus Systemic lupus erythematosus (SLE) is the most common ...

  15. High mass clearance of autoantibodies from a murine model of lupus nephritis by immunoadsorption using star-configured polyethylene glycols.

    PubMed

    Ross, E A; Branham, M L; Tebbett, I R

    2001-04-01

    The extracorporeal immunoadsorption of antibodies as part of the therapy for human autoimmune diseases has been limited by technology with inadequate and nonselective mass clearance or problems with bioincompatibility. To overcome these shortcomings, we designed a method utilizing star-configured polyethylene glycols (star-PEGs) having up to 63 free arms with immunoreactive (tresylate ester) end-groups for each arm immobilized to a polymer support substrate. The flexibility and length of the arms are thought to allow optimization of epitope presentation and to permit interaction with immunoligands on adjacent arms. To demonstrate efficacy we used an in vitro murine antibody model of human lupus nephritis, wherein we could study the kinetics and mass clearance of hybridoma derived antihistone antibodies from human plasma. Histones were covalently bound to the star-PEG end-groups and the kinetics of antibody adsorption were assessed using a surface plasmon resonance technique. The equilibrium constants of antihistone antibody binding to histone-star-PEGs that were linked to a support grid demonstrated high affinity with a KA of 3.56E + 07 and a KD of 2.81E - 08. The optimum reaction conditions were determined to accomplish the hydrophilization of polysulfone (PS; by an aqueous nitration method) and polymethylmethacrylate substrates (PMMA; by hydrazine), using sheet casts of both polymer substances. Hollow fiber devices of these polymers (commercial hemodialyzers) were modified so that histone-bound star-PEGs were linked to their intracapillary luminal surfaces, using a process which we have shown retains their immunoadsorption properties for antihistone antibodies. A closed loop recirculating model was constructed to measure mass clearance of antibodies from a reservoir. After optimizing conditions using extraction from saline solutions, the removal of antibody from human plasma by control and surface-modified devices was assessed over 4 h. There was no measurable

  16. Lupus

    MedlinePlus

    If you have lupus, your immune system attacks healthy cells and tissues by mistake. This can damage your joints, skin, blood vessels and organs. There are many kinds of lupus. The most common type, systemic lupus erythematosus, affects ...

  17. The Efficacy and Safety of Leflunomide for the Treatment of Lupus Nephritis in Chinese Patients: Systematic Review and Meta-Analysis

    PubMed Central

    Cao, Heng; Rao, Yuefeng; Liu, Lin; Lin, Jin; Yang, Hongyu; Zhang, Xingguo; Chen, Zhong

    2015-01-01

    Objective To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis. Methods A systematic review evaluating the efficacy and safety of leflunomide compared with cyclophosphamide in adult patients with LN was performed. Data from relevant randomized controlled trials (RCTs) performed before December 2014 was collected from several databases (PubMed, Embase, Cochrane Library, CNKI and CBM). No language restrictions were applied. Efficacy outcomes included overall remission, SLE Disease Activity Index (SLEDAI) score, 24-hour proteinuria and serum creatinine. Safety data were analyzed. The effects of treatment on these outcomes were summarized as relative risks (RRs) with 95% confidence intervals (CIs) and mean differences were pooled using a fixed or random effects model. Results Eleven RCTs with Jadad score of 3 or greater were identified and included a total of 254 patients. Cyclophosphamide was served as the control drug in all trials. The SLEDAI score, urine protein level and serum creatinine decreased significantly following leflunomide treatment (P<0.05). Leflunomide was superior to cyclophosphamide in achieving complete and total remission, but no difference in SLEDAI score was found between these two treatments (P>0.05). Additionally, patients receiving leflunomide treatment showed favorable renal function profiles, especially regarding the 24-hour proteinuria (mean difference: -0.58, 95%CI: -0.78~-0.37, P<0.01) and serum creatinine (mean difference: -0.20, 95%CI: -0.39~-0.01, P<0.05). In the safety comparison, leflunomide was safer than cyclophosphamide regarding adverse drug reactions (ADRs), including liver damage (RR = 0.53, 95%CI: 0.33~0.87, P<0.05), alopecia (RR = 0.38, 95%CI: 0.17~0.85, P<0.05), leukopenia (RR = 0.25, 95%CI: 0.08~0.77, P<0.05) and infection (RR = 0.54, 95%CI: 0.32~0.92, P<0.05), without increased risk of gastrointestinal reaction, rash or herpes zoster

  18. TLR2 Plays a Critical Role in HMGB1-Induced Glomeruli Cell Proliferation Through the FoxO1 Signaling Pathway in Lupus Nephritis.

    PubMed

    Feng, Xiao-Juan; Wu, Chao; Yang, Gui-Fang; Liu, Qing-Juan; Liu, Jin-Xi; Hao, Jun; Xing, Ling-Ling; Yang, Min; Liu, Shu-Xia

    2016-04-01

    The objective of this study was to examine the role and possible mechanisms of toll-like receptor 2 (TLR2) in high-mobility group box chromosomal protein 1 (HMGB1)-induced mouse mesangial cell (MMC) proliferation and glomeruli proliferation of MRL/Fas(lpr) mice. First, the expression of proliferating cell nuclear antigen (PCNA), TLR2 and Forkhead box protein O1 (FoxO1) messenger RNA (mRNA) and protein in the glomeruli of MRL/Fas(lpr) mice was quantified, and the correlation with cell proliferation of glomeruli was analyzed. Then, lipopolysaccharide (LPS), TLR2 neutralization antibody, and small hairpin TLR2 (shTLR2) were used to confirm the role of TLR2 in HMGB1-induced MMC proliferation. Furthermore, wild-type FoxO1 (WT-FoxO1) vector was used to investigate the effect of FoxO1 pathway on HMGB1-induced MMC proliferation. Finally, electroporation was used to knockdown TLR2 in the glomeruli of MRL/Fas(lpr) mice, and renal function, FoxO1, and PCNA expression were detected. The results showed that the TLR2 expression was upregulated and FoxO1 expression was decreased in the glomeruli of MRL/Fas(lpr) mice, and these effects were significantly correlated with cell proliferation of the glomeruli. In vitro, the TLR2 neutralization antibody and the WT-FoxO1 vector, both reduced the MMC proliferation levels induced by HMGB1. The TLR2 neutralization antibody also blocked the HMGB1-dependent activation of the FoxO1 pathway and cell proliferation. In addition, transfection with shTLR2 decreased the proliferation levels and PCNA expression induced by HMGB1. In vivo, treatment with shTLR2 significantly reduced the PCNA expression in the glomeruli of MRL/Fas(lpr) mice and improved renal function. In addition, treatment with shTLR2 or blocking of TLR2 also reduced the translocation of FoxO1. Thus, TLR2 plays a critical role in HMGB1-induced glomeruli cell proliferation through the FoxO1 signaling pathway in lupus nephritis. PMID:26799193

  19. Human embryonic stem cell-derived mesenchymal cells preserve kidney function and extend lifespan in NZB/W F1 mouse model of lupus nephritis.

    PubMed

    Thiel, Austin; Yavanian, Gregory; Nastke, Maria-Dorothea; Morales, Peter; Kouris, Nicholas A; Kimbrel, Erin A; Lanza, Robert

    2015-01-01

    Adult tissue-derived mesenchymal stromal cells (MSCs) are showing promise in clinical trials for systemic lupus erythematosus (SLE). However, the inability to manufacture large quantities of functional cells from a single donor as well as donor-dependent variability in quality limits their clinical utility. Human embryonic stem cell (hESC)-derived MSCs are an alternative to adult MSCs that can circumvent issues regarding scalability and consistent quality due to their derivation from a renewable starting material. Here, we show that hESC-MSCs prevent the progression of fatal lupus nephritis (LN) in NZB/W F1 (BWF1) mice. Treatment led to statistically significant reductions in proteinuria and serum creatinine and preserved renal architecture. Specifically, hESC-MSC treatment prevented disease-associated interstitial inflammation, protein cast deposition, and infiltration of CD3(+) lymphocytes in the kidneys. This therapy also led to significant reductions in serum levels of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), two inflammatory cytokines associated with SLE. Mechanistically, in vitro data support these findings, as co-culture of hESC-MSCs with lipopolysaccharide (LPS)-stimulated BWF1 lymphocytes decreased lymphocyte secretion of TNFα and IL-6, and enhanced the percentage of putative regulatory T cells. This study represents an important step in the development of a commercially scalable and efficacious cell therapy for SLE/LN. PMID:26628350

  20. miR-410 suppresses the expression of interleukin-6 as well as renal fibrosis in the pathogenesis of lupus nephritis.

    PubMed

    Liu, Dongmei; Zhang, Na; Zhang, Jing; Zhao, Haiyan; Wang, Xiaofei

    2016-06-01

    Lupus nephritis (LN) is a highly complex autoimmune disease caused by systemic lupus erythematosus (SLE). MicroRNAs (miRNAs) play a vital role in the pathogenesis of SLE. Previously, a total of 29 miRNAs were identified to be down-regulated in SLE patients, in which miR-410 was likely to be involved in the signalling transduction pathways in regulating the pathogenesis of SLE. The purpose of this study was to investigate the role of miR-410 in LN and to find out whether miR-410 regulates the expression of interleukin (IL)-6 and fibrosis in LN. It was found that the expression level of miR-410 in kidney tissue of MRL/lpr mice was decreased compared to that in BALB/C mice, whereas the level of IL-6 was overexpressed in MRL/lpr mice. Luciferase assay showed that miR-410 binds directly to the 3' untranslated region (UTR) of IL-6, with the results showing that overexpression of miR-410 significantly decreased the expression level of IL-6 in SV40MES13 cells. Moreover, overexpression of miR-410 significantly reduced the expression levels of fibrosis factors such as transforming growth factor-β1 (TGF-β1) and collagen I/III in SV40MES13 cells; Inhibition of the expression of miR-410 with miR-410 inhibitor resulted in increased levels of IL-6 as well as fibrosis factors. The results identify that miR-410, as a novel and critical factor in the pathogenesis of LN, decreases IL-6 expression by binding directly to the 3'UTR and suppresses fibrosis through down-regulation of TGF-β1 in SV40MES13 cells. Our study brings new insight into understanding the complex mechanisms involved in the pathogenesis of lupus disease. PMID:27028192

  1. Essential Requirement for IFN Regulatory Factor 7 in Autoantibody Production but Not Development of Nephritis in Murine Lupus.

    PubMed

    Miyagawa, Fumi; Tagaya, Yutaka; Ozato, Keiko; Asada, Hideo

    2016-09-15

    Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the production of autoantibodies against nuclear components. Recent genetic studies of SLE patients have revealed that IFN regulatory factor (IRF) 7 gene polymorphisms are associated with an increased risk of SLE, but the precise role of IRF7 in SLE development is not fully understood. We investigated the role of IRF7 in the pathogenesis of SLE using a mouse model and saw a curious dissociation of autoantibody production and development of glomerulonephritis. SLE was chemically induced into IRF7-deficient mice, and glomerulonephritis with deposits of IgG and lipogranulomas were observed after 10 mo. However, these mice failed to produce anti-dsDNA, ssDNA, ribonucleoprotein, and Sm autoantibodies. Following the chemical induction, IRF7-deficient mice expressed substantially lower levels of IFN-stimulated genes than did wild-type mice, but NF-κB target genes were equally upregulated in both strains. Therefore, the type I IFN pathway seems critical for the autoantibody production, but the NF-κB activation is sufficient for the development of glomerulonephritis in this model. Our study thus demonstrates a specific requirement for IRF7 in autoantibody production and uncovers a new layer of complexity in the pathogenesis of SLE. PMID:27527596

  2. Up-regulation of Serum MiR-130b-3p Level is Associated with Renal Damage in Early Lupus Nephritis

    NASA Astrophysics Data System (ADS)

    Wang, Wanpeng; Mou, Shan; Wang, Ling; Zhang, Minfang; Shao, Xinghua; Fang, Wei; Lu, Renhua; Qi, Chaojun; Fan, Zhuping; Cao, Qin; Wang, Qin; Fang, Yan; Ni, Zhaohui

    2015-08-01

    Systemic lupus erythematosus (SLE) is a common but severe autoimmune systemic inflammatory disease. Lupus nephritis (LN) is a serious complication of SLE,affecting up to 70% of SLE patients. Circulating microRNAs (miRNA) are emerging as biomarkers for pathological conditions and play significant roles in intercellular communication. In present research, serum samples from healthy control, early and late stage LN patients were used to analyze the expression profile of miRNAs by microarray. Subsequent study demonstrated that miR-130b-3p in serum of patients with early stage LN were significantly up-regulated when compared with healthy controls. In addition,we have also observed that the expression of a large amount of circulating microRNAs significantly decreased in patients with late stage LN. The further analysis found that the expression of serum miR-130b-3p was positively correlated with 24-hour proteinuria and renal chronicity index in patients with early stage LN.Transfection of renal tubular cellline(HK-2)with miR-130b-3p mimics can promote epithelial-mesenchymal transition (EMT). The opposite effects were observed when transfected with miR-130b-3p inhibitors. MiR-130b-3p negatively regulated ERBB2IP expression by directly targeting the 3‧-UTR of ERBB2IP The circulating miR-130b-3p might serve as a biomarker and play an important role in renal damage in early stage LN patients.

  3. Accelerated Pathological and Clinical Nephritis in Systemic Lupus Erythematosus-Prone New Zealand Mixed 2328 Mice Doubly Deficient in TNF Receptor 1 and TNF Receptor 2 via a Th17-Associated Pathway1

    PubMed Central

    Jacob, Noam; Yang, Haitao; Pricop, Luminita; Liu, Yi; Gao, Xiaoni; Zheng, Song Guo; Wang, Juhua; Gao, Hua-Xin; Putterman, Chaim; Koss, Michael N.; Stohl, William; Jacob, Chaim O.

    2009-01-01

    TNF-α has both proinflammatory and immunoregulatory functions. Whereas a protective role for TNF administration in systemic lupus erythematosus (SLE)-prone (New Zealand Black × New Zealand White)F1 mice has been established, it remains uncertain whether this effect segregates at the individual TNFR. We generated SLE-prone New Zealand Mixed 2328 mice genetically deficient in TNFR1, in TNFR2, or in both receptors. Doubly-deficient mice developed accelerated pathological and clinical nephritis with elevated levels of circulating IgG anti-dsDNA autoantibodies and increased numbers of CD4+ T lymphocytes, especially activated memory (CD44highCD62Llow) CD4+ T cells. We show that these cells expressed a Th17 gene profile, were positive for IL-17 intracellular staining by FACS, and produced exogenous IL-17 in culture. In contrast, immunological, pathological, and clinical profiles of mice deficient in either TNFR alone did not differ from those in each other or from those in wild-type controls. Thus, total ablation of TNF-α-mediated signaling was highly deleterious to the host in the New Zealand Mixed 2328 SLE model. These observations may have profound ramifications for the use of TNF and TNFR antagonists in human SLE and related autoimmune disorders, as well as demonstrate, for the first time, the association of the Th17 pathway with an animal model of SLE. PMID:19201910

  4. Interstitial Nephritis

    MedlinePlus

    ... rye-tus) is a kidney disorder. The kidneys filter waste and extra fluid from the body. Interstitial nephritis reduces the kidneys’ ability to filter properly. Interstitial nephritis is a serious condition, but ...

  5. Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Perez-Hernandez, Javier; Forner, Maria J.; Pinto, Carolina; Chaves, Felipe J.

    2015-01-01

    There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers. PMID:26390437

  6. Lupus and pregnancy.

    PubMed

    Baer, Alan N; Witter, Frank R; Petri, Michelle

    2011-10-01

    Systemic lupus erythematosus (SLE) disproportionately affects women in their reproductive age years. Pregnancy in this systemic autoimmune disease has long been associated with poor obstetric outcomes. However, the frequency of pregnancy loss in lupus has dropped to a level commensurate with that of the general US population. The outcomes of lupus pregnancies are better if conception is delayed until the disease has been inactive for at least 6 months, and the medication regimen has been adjusted in advance. Pregnancy in lupus is prone to complications, including flares of disease activity during pregnancy or in the postpartum period, preeclampsia, miscarriage, stillbirth, intrauterine growth retardation, and preterm birth. Active lupus nephritis poses the greatest risk. The recognition of a lupus flare during pregnancy may be difficult because the signs and symptoms may mimic those of normal pregnancy. Monitoring should include baseline and monthly laboratory tests, serial ultrasonography, fetal surveillance tests, and fetal m-mode echocardiography for mothers with SS-A (Ro) or SS-B (La) antibodies. In the absence of any signs or symptoms of active SLE, affected patients require no specific treatment during pregnancy. If hydroxychloroquine was in use before conception, it should be maintained throughout pregnancy. If a woman with SLE has antiphospholipid antibodies, prophylactic treatment with aspirin and/or low-molecular weight heparin is indicated to prevent fetal loss. Lupus flares during pregnancy are generally treated with hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone, and azathioprine. High-dose prednisone and cyclophosphamide are reserved for severe lupus complications but are associated with significant pregnancy-related complications and poor obstetrical outcomes. PMID:22112525

  7. A multicentre, randomised controlled study of enteric-coated mycophenolate sodium for the treatment of relapsed or resistant proliferative lupus nephritis: an Asian experience

    PubMed Central

    Anutrakulchai, Sirirat; Panaput, Thanachai; Wongchinsri, Jeerapat; Chaishayanon, Somchai; Satirapoj, Bancha; Traitanon, Opas; Pima, Warabhorn; Rukrung, Chutima; Thinkhamrop, Bandit; Avihingsanon, Yingyos

    2016-01-01

    Objective The optimal treatment of relapse or resistant lupus nephritis (LN) is still unclear. Mycophenolate might be an alternative therapy to avoid toxicities of cyclophosphamide (CYC). This study was aimed to compare enteric-coated mycophenolate sodium (EC-MPS) versus intravenous CYC as an induction therapy. Methods The study was a 12-month period of multicentre, open-labelled randomised controlled trial. Fifty-nine patients who had relapsed (36%) or who were resistant to previous CYC treatment (64%) and all who were biopsy-proven class III/IV, were randomised into CYC (n=32) and EC-MPS groups (n=27). The CYC group received intravenous CYC 0.5–1 g/m2 monthly and the EC-MPS group was treated with EC-MPS 1440 mg/day for first 6 months. After induction therapy, both groups received EC-MPS 720 mg/day until the end of study at 12 months. Results The study was prematurely terminated due to high rate of serious adverse events in CYC arm. Death and serious infections were observed more in the CYC group (15.6% in CYC and 3.5% in EC-MPS; p=0.04). The early discontinuation rates, mainly from serious infections, were significantly higher in CYC group (percentage differences of 16.9; 95% CI 1.3 to 32.4). At the 12th month, both arms were comparable in terms of complete and partial remission rates (68% CYC and 71% EC-MPS) and times to remission (96 days CYC and 97 days EC-MPS). Composites of unfavourable outcomes (death, doubling of serum creatinine, non-remission and intolerance to treatment) were 46.9% and 37% in CYC and EC-MPS (risk difference=9.84; p=0.44). Conclusions EC-MPS may have comparable efficacy, but was better tolerated than CYC. EC-MPS should be an alternative choice of treatment for difficult-to-treat LN, particularly in CYC-experienced LN patients. Due to an early termination of the study, further clinical implementation could be cautiously used. Trial registration number Clinicaltrials.gov ID#NCT01015456. PMID:26835147

  8. 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.

  9. Total lymphoid irradiation in refractory systemic lupus erythematosus

    SciTech Connect

    Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.

    1986-07-01

    In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

  10. 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

  11. Comparative effects of n-3, n-6 and n-9 unsaturated fatty acid-rich diet consumption on lupus nephritis, autoantibody production and CD4+ T cell-related gene responses in the autoimmune NZBWF1 mouse.

    PubMed

    Pestka, James J; Vines, Laura L; Bates, Melissa A; He, Kaiyu; Langohr, Ingeborg

    2014-01-01

    Mortality from systemic lupus erythematosus (SLE), a prototypical autoimmune disease, correlates with the onset and severity of kidney glomerulonephritis. There are both preclinical and clinical evidence that SLE patients may benefit from consumption of n-3 polyunsaturated fatty acids (PUFA) found in fish oil, but the mechanisms remain unclear. Here we employed the NZBWF1 SLE mouse model to compare the effects of dietary lipids on the onset and severity of autoimmune glomerulonephritis after consuming: 1) n-3 PUFA-rich diet containing docosahexaenoic acid-enriched fish oil (DFO), 2) n-6 PUFA-rich Western-type diet containing corn oil (CRN) or 3) n-9 monounsaturated fatty acid (MUFA)-rich Mediterranean-type diet containing high oleic safflower oil (HOS). Elevated plasma autoantibodies, proteinuria and glomerulonephritis were evident in mice fed either the n-6 PUFA or n-9 MUFA diets, however, all three endpoints were markedly attenuated in mice that consumed the n-3 PUFA diet until 34 wk of age. A focused PCR array was used to relate these findings to the expression of 84 genes associated with CD4+ T cell function in the spleen and kidney both prior to and after the onset of the autoimmune nephritis. n-3 PUFA suppression of autoimmunity in NZBWF1 mice was found to co-occur with a generalized downregulation of CD4+ T cell-related genes in kidney and/or spleen at wk 34. These genes were associated with the inflammatory response, antigen presentation, T cell activation, B cell activation/differentiation and leukocyte recruitment. Quantitative RT-PCR of representative affected genes confirmed that n-3 PUFA consumption was associated with reduced expression of CD80, CTLA-4, IL-10, IL-18, CCL-5, CXCR3, IL-6, TNF-α and osteopontin mRNAs in kidney and/or spleens as compared to mice fed n-6 PUFA or n-9 MUFA diets. Remarkably, many of the genes identified in this study are currently under consideration as biomarkers and/or biotherapeutic targets for SLE and other autoimmune

  12. Piperlongumine alleviates lupus nephritis in MRL-Fas(lpr) mice by regulating the frequency of Th17 and regulatory T cells.

    PubMed

    Yao, Lan; Chen, Hai-ping; Ma, Qing

    2014-09-01

    Recent data have shown that piperlongumine (PL), an important component of Piper longum fruits, is known to possess anti-inflammatory and vascular-protective activities. This study aimed to examine the therapeutic effects and underlying mechanisms of PL on lupus-prone MRL-Fas(lpr) mice. Female MRL-Fas(lpr) mice were intraperitoneally treated with PL (2.4 mg kg(-1) d(-1)) for 10 weeks, and the proteinuria level was biweekly monitored. After the mice were euthanized, serum biochemical parameters and renal damage were determined. Splenocytes of MRL-Fas(lpr) mice were isolated for in vitro study. Treatment of the mice with PL significantly attenuated the progression of proteinuria and glomerulonephritis. The improvement was accompanied by decreased serum levels of nephritogenic anti-dsDNA antibodies, IL-6, IL-17, IL-23 and TNF-α. Treatment of the mice with PL suppressed the frequency of Th17 cells and increased the regulatory T cells (Tregs). In vitro, the levels of IL-6, IL-17, IL-23 and TNF-α were significantly decreased in the cultures of splenocytes from PL-treated mice compared with those from vehicle-treated mice. In addition, PL treatment impeded activation of the JAK/STAT3 signaling in splenocytes. Of great important, the survival of MRL-Fas(lpr) mice were improved by PL treatment. In summary, PL effectively ameliorates lupus syndrome in MRL-Fas(lpr) mice by suppressing the pathogenic Th17 cells and increasing the Tregs as well as inhibiting activation of the JAK/STAT3 signaling pathway. This study sheds new light on the immune-modulatory role of PL. PMID:24837470

  13. Lupus and Kidney Disease (Lupus Nephritis)

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  14. 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

  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. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. An Extract of Antrodia camphorata Mycelia Attenuates the Progression of Nephritis in Systemic Lupus Erythematosus-Prone NZB/W F1 Mice

    PubMed Central

    Chang, Jia-Ming; Lee, Yi-Ru; Hung, Le-Mei; Liu, Sheng-Yung; Kuo, Mao-Tien; Wen, Wu-Che; Chen, Peini

    2011-01-01

    Antrodia camphorata is used in folk medicine for the treatment of inflammation syndromes and liver-related diseases in Taiwan. The goal of this study was to evaluate the efficacy of the mycelial extract of A. camphorata (ACE) for the treatment of systemic lupus erythematosus (SLE) in SLE-prone NZB/W F1 mice. After antibodies against double-stranded DNA appeared in NZB/W mice, the mice were orally administered varying dosages of ACE (100, 200 and 400 mg kg−1) for 5 consecutive days per week for 12 weeks via gavage. To assess the efficacy of ACE, we measured SLE-associated biochemical and histopathological biomarkers levels of blood urine nitrogen (BUN), blood creatinine, urine protein and urine creatinine and thickness of the kidney glomerular basement membrane by staining with periodic acid-Schiff. Antroquinonol, an active component of ACE, was investigated for anti-inflammation activity in lipopolysaccharide-induced RAW 267.4 cells. ACE at 400 mg kg−1 significantly suppressed urine protein and serum BUN levels and decreased the thickness of the kidney glomerular basement membrane. Antroquinonol significantly inhibited the production of tumor necrosis factor-α and interleukin-1β by 75 and 78%, respectively. In conclusion, ACE reduced urine protein and creatinine levels and suppressed the thickening of the kidney glomerular basement membrane, suggesting that ACE protects the kidney from immunological damage resulting from autoimmune disease. PMID:18955361

  2. [An autopsied case of chronic active Epstein-Barr virus infection complicated in systemic lupus erythematosus and antiphospholipid antibody syndrome].

    PubMed

    Ogawa, Jun; Koike, Ryuji; Sugihara, Takahiko; Hagiyama, Hiroyuki; Nishio, Junko; Kohsaka, Hitoshi; Kubota, Tetsuo; Kawachi, Hiroshi; Kasahara, Ichiro; Miyasaka, Nobuyuki

    2002-12-01

    We have experienced a case of chronic active Epstein-Barr virus infection (CAEBV) complicated in systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS). A 35-year-old woman was admitted to our hospital with complaints of fever and dyspnea on exertion. She was diagnosed as having SLE on the basis of arthritis, oropharyngeal ulcer, lymphopenia, and positive autoantibodies against DNA, RNP and SSA. The diagnosis of APS was also made because of positive anti-cardiolipin IgG antibodies and the existence of multiple pulmonary infarction with pulmonary hypertension. The administration of 30 mg/day of prednisolone and anti-coagulation significantly improved clinical symptoms. However, she was again admitted to the hospital four months later because of progressive liver damage and pancytopenia. Increment of prednisolone did not improve the clinical situation and she expired because of pulmonary hemorrhage. At autopsy, there were a significant increase of histiocytes with hemophagocytosis and a dense infiltration of atypical lymphocytes in the liver, spleen, lymph nodes and bone marrow. Infiltrated lymphocytes were positive for CD 3 and EBER 1 in immunohistochemical staining and EBVmRNA was detected by in situ hybridization. Final pathological diagnosis was CAEBV with hemophagocytic syndrome in association with lupus nephritis, pulmonary hemorrhage and pulmonary infarction. PMID:12599514

  3. Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor. alpha. : Relevance to genetic predisposition to systemic lupus erythematosus

    SciTech Connect

    Jacob, C.O.; Fronek, Z.; Koo, M.; McDevitt, H.O. ); Lewis, G.C. ); Hansen, J.A. )

    1990-02-01

    The authors report on the production of tumor necrosis factor (TNF)-{alpha} and TNF-{beta} by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-{alpha}, whereas DR3- and DR4-positive subjects show high levels of TNF-{alpha} production. No correlation between TNF-{alpha} levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-{alpha} inducibility; this genotype is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-{alpha} production. DR4 haplotype is associated with high TNF-{alpha} inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.

  4. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

    PubMed

    Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

    2014-01-01

    Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term. PMID:24213308

  5. Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus

    SciTech Connect

    Wener, M.H.; Mannik, M.; Schwartz, M.M.; Lewis, E.J.

    1987-03-01

    Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc).

  6. 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

  7. Childhood-onset systemic lupus erythematosus.

    PubMed Central

    Olowu, Wasiu

    2007-01-01

    OBJECTIVES: To describe the initial clinicolaboratory manifestations and short-term outcome in a series of Nigerian children with systemic lupus erythematosus (SLE). METHODS: A nonrandomized prospective study of consecutive cases of childhood-onset SLE. Baseline and follow-up clinicolaboratory data were collected and analyzed. Each patient was followed up for 12 months. RESULTS: Eleven children were studied. There were seven girls (F:M, 1.75). Mean ages at lupus onset and diagnosis were 10.0 +/- 2.53 years and 11.2 +/- 2.53 years, respectively. Mean time at onset of renal disease following SLE symptoms onset was 1.22 +/- 0.93 years. All cases were misdiagnosed prior to presentation; diagnosis was delayed in nine patients. Lupus activity was mild, moderate and severe in two, five and four patients, respectively. Hypertension (n = 5), nephrotic syndrome (n = 6), microerythrocyturia (n = 6) and acute renal failure (n = 7) were associated morbidities. Of the 27 presenting clinical features, 17 were nondiagnostic, while 10 were diagnostic. Fever (n = 9) was a major nondiagnostic symptom; major diagnostic manifestations were lupus nephritis (n = 11), arthritis (n = 10) and serositis (n = 7). Catastrophic antiphospholipid syndrome was diagnosed in three. The glomerular lesions were nonproliferative (n = 1), focal (n = 3) and diffuse (n = 7) proliferative lupus nephritis. Complete remission rate at end-point was 71.4%. Fourteen percent of the patients relapsed. Renal survival and mortality rates were 86.0% and 30.0%, respectively. CONCLUSION: In this study, severe renal and extrarenal comorbidities were common; mortality rate was also high. High frequency of misdiagnosis and delayed diagnosis were probably responsible for these. PMID:17668644

  8. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis

    PubMed Central

    Bertsias, George K; Tektonidou, Maria; Amoura, Zahir; Aringer, Martin; Bajema, Ingeborg; Berden, Jo H M; Boletis, John; Cervera, Ricard; Dörner, Thomas; Doria, Andrea; Ferrario, Franco; Floege, Jürgen; Houssiau, Frederic A; Ioannidis, John P A; Isenberg, David A; Kallenberg, Cees G M; Lightstone, Liz; Marks, Stephen D; Martini, Alberto; Moroni, Gabriela; Neumann, Irmgard; Praga, Manuel; Schneider, Matthias; Starra, Argyre; Tesar, Vladimir; Vasconcelos, Carlos; van Vollenhoven, Ronald F; Zakharova, Helena; Haubitz, Marion; Gordon, Caroline; Jayne, David; Boumpas, Dimitrios T

    2012-01-01

    Objectives To develop recommendations for the management of adult and paediatric lupus nephritis (LN). Methods The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus. Results Immunosuppressive treatment should be guided by renal biopsy, and aiming for complete renal response (proteinuria <0.5 g/24 h with normal or near-normal renal function). Hydroxychloroquine is recommended for all patients with LN. Because of a more favourable efficacy/toxicity ratio, as initial treatment for patients with class III–IVA or A/C (±V) LN according to the International Society of Nephrology/Renal Pathology Society 2003 classification, mycophenolic acid (MPA) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. In patients with adverse clinical or histological features, CY can be prescribed at higher doses, while azathioprine is an alternative for milder cases. For pure class V LN with nephrotic-range proteinuria, MPA in combination with oral glucocorticoids is recommended as initial treatment. In patients improving after initial treatment, subsequent immunosuppression with MPA or azathioprine is recommended for at least 3 years; in such cases, initial treatment with MPA should be followed by MPA. For MPA or CY failures, switching to the other agent, or to rituximab, is the suggested course of action. In anticipation of pregnancy, patients should be switched to appropriate medications without reducing the intensity of treatment. There is no evidence to suggest that management of LN should differ in children versus adults. Conclusions Recommendations for the management of LN were developed using an evidence-based approach followed by expert consensus. PMID:22851469

  9. Development of Th17-associated interstitial kidney inflammation in lupus-prone mice lacking the gene encoding Signal Transduction and Activator of Transcription-1 (STAT-1)

    PubMed Central

    Yiu, Gloria; Rasmussen, Tue Kruse; Ajami, Bahareh; Haddon, David J.; Chu, Alvina D.; Tangsombatvisit, Stephanie; Haynes, Winston A.; Diep, Vivian; Steinman, Larry; Faix, James; Utz, Paul J.

    2016-01-01

    Type I interferon (IFN-I) signaling is a central pathogenic pathway in Systemic Lupus Erythematosus (SLE), and therapeutics targeting IFN-I signaling are in development. Multiple proteins with overlapping function participate in IFN signaling, but the signaling events downstream of receptor engagement are unclear. We employed highly-multiplexed assays to characterize autoantibody production, cytokine/chemokine profiles, and Signal Transduction and Activators of Transcription (STAT) phosphorylation to investigate the individual roles of IFNAR2, IRF9 and STAT1 in MRL/lpr (lpr) mice. Surprisingly, we found that Stat1−/−, but not Irf9−/− or Ifnar2−/− mice, developed interstitial nephritis characterized by infiltration with RORγT+ lymphocytes, macrophages and eosinophils. Despite pronounced interstitial kidney disease and abnormal kidney function, Stat1−/− mice had decreased proteinuria, glomerulonephritis and autoantibody production. Phospho-specific flow cytometry (phosphoflow) revealed shunting of STAT phosphorylation from STAT1 to STAT3/4. In summary, we describe unique contributions of STAT1 to pathology in different kidney compartments, and provide novel insight into tubulointerstitial nephritis (TIN) a poorly understood complication that predicts end-stage kidney disease in SLE patients. PMID:26636548

  10. Btk inhibition treats TLR7/IFN driven murine lupus.

    PubMed

    Bender, Andrew T; Pereira, Albertina; Fu, Kai; Samy, Eileen; Wu, Yin; Liu-Bujalski, Lesley; Caldwell, Richard; Chen, Yi-Ying; Tian, Hui; Morandi, Federica; Head, Jared; Koehler, Ursula; Genest, Melinda; Okitsu, Shinji L; Xu, Daigen; Grenningloh, Roland

    2016-03-01

    Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane-induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors. In vitro studies using primary human macrophages revealed that Btk inhibition can block activation by immune complexes and TLR7 which contributes to tissue damage in SLE. Overall, our results provide translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling. PMID:26821304

  11. Anti-chromatin antibodies in systemic lupus erythematosus: a useful marker for lupus nephropathy

    PubMed Central

    Cervera, R; Vinas, O; Ramos-Casals, M; Font, J; Garcia-Carrasco, M; Siso, A; Ramirez, F; Machuca, Y; Vives, J; Ingelmo, M; Burlingame, R

    2003-01-01

    Background: Anti-chromatin antibodies have recently been described in patients with systemic lupus erythematosus (SLE) and it has been suggested that their presence is associated with lupus nephritis. Objective: To assess the prevalence and clinical associations of these antibodies in SLE. Methods: The presence of anti-chromatin antibodies in 100 patients with SLE was investigated by an enzyme linked immunosorbent assay (ELISA). To determine the specificity of these antibodies, 100 patients with primary Sjögren's syndrome, 30 with primary antiphospholipid syndrome (APS), 10 with systemic sclerosis, and 100 normal controls were also tested. Results: Positive levels were detected in 69/100 (69%) patients with SLE. In contrast, they were found in only 8/100 (8%) of those with primary Sjögren's syndrome, in 1/10 (10%) with systemic sclerosis, in 2/30 (7%) with primary APS, and in none of the 100 healthy controls. Patients with anti-chromatin antibodies had a twofold higher prevalence of lupus nephropathy than those without these antibodies (58% v 29%, p<0.01). A significant correlation was found between the levels of anti-chromatin antibodies and disease activity score as measured by the European Consensus Lupus Activity Measurement (ECLAM; p=0.011). Conclusions: The measurement of anti-chromatin antibodies appears to be a useful addition to the laboratory tests that can help in the diagnosis and treatment of SLE. These antibodies are both sensitive and specific for SLE, and are a useful marker for an increased risk of lupus nephritis. PMID:12695155

  12. 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

  13. Collapsing focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus.

    PubMed

    Tariq, Hassan; Rafiq, Arsalan; Franchin, Giovanni

    2014-01-01

    We present a case of a 36-year-old female from Ghana who presented with atypical chest pain and shortness of breath and was found to have bilateral transudative pleural effusion and trivial pericardial effusion. Further work-up revealed serological markers consistent with active lupus and negative HIV. She developed rapid deterioration of her renal function requiring dialysis. Her renal biopsy showed collapsing focal segmental glomerulosclerosis with diffuse mesangial proliferative glomerulonephritis, consistent with lupus nephritis class II along with tubular degenerative changes. She was started on high dose steroids and later on mycophenolate mofetil. Her renal function slowly recovered to baseline. PMID:25180039

  14. Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils.

    PubMed

    Jiang, X; Khursigara, G; Rubin, R L

    1994-11-01

    Drug-induced lupus is a serious side effect of certain medications, but the chemical features that confer this property and the underlying pathogenesis are puzzling. Prototypes of all six therapeutic classes of lupus-inducing drugs were highly cytotoxic only in the presence of activated neutrophils. Removal of extracellular hydrogen peroxide before, but not after, exposure of the drug to activated neutrophils prevented cytotoxicity. Neutrophil-dependent cytotoxicity required the enzymatic action of myeloperoxidase, resulting in the chemical transformation of the drug to a reactive product. The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo. PMID:7973636

  15. Understanding Lupus

    MedlinePlus

    ... treat lupus? What causes lupus? What are the risk factors for developing lupus? How does lupus affect the nervous system? What is the history of lupus? Is stress related to lupus? Can hormones trigger the development ...

  16. Coincidence of tuberous sclerosis and systemic lupus erythematosus-a case report.

    PubMed

    Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis

    2016-01-01

    Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest. PMID:26526985

  17. Evaluation of Clinical Outcomes and Renal Vascular Pathology among Patients with Lupus

    PubMed Central

    Barber, Claire; Herzenberg, Andrew; Aghdassi, Ellie; Su, Jiandong; Lou, Wendy; Qian, Gan; Yip, Jonathan; Nasr, Samih H.; Thomas, David; Scholey, James W.; Wither, Joan; Urowitz, Murray; Gladman, Dafna; Reich, Heather

    2012-01-01

    Summary Background and objectives The objective of this study was to determine the clinical significance of renal vascular lesions in lupus nephritis. Design, setting, participants, & measurements Renal vascular lesions defined as thrombotic microangiopathy, lupus vasculopathy, uncomplicated vascular immune deposits, and arterial sclerosis were evaluated in relation to renal and vascular morbidity and overall mortality. Results Biopsies from 161 patients revealed thrombotic microangiopathy (13), lupus vasculopathy (5), and arterial sclerosis (93). No renal vascular lesions were found in 24.8% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older (arterial sclerosis=37.9±13.0 and lupus vasculopathy=44.4±8.9 versus controls=33.1±8.9 years, P<0.05), and the mean arterial pressure was higher in all groups compared with controls. Nephritis subtype, activity indices, and proteinuria were similar between groups, estimated GFR was lower in arterial sclerosis (70.5±33.3 versus 84.5±26.6 ml/min per 1.73 m2, P=0.03), and chronicity index (thrombotic microangiopathy=3.5, lupus vasculopathy=4.5, and arterial sclerosis=2.5) was higher in all renal vascular lesions subgroups versus controls (1.0, P<0.05). In 133 patients with similar follow-up, the association between renal vascular lesions and vascular events was significant (Fisher exact test, P=0.002) and remained so after multivariate analysis (exact conditional scores test, P=0.04), where the difference between arterial sclerosis and uncomplicated vascular immune deposits was most noticeable (odds ratio [95% confidence interval]=8.35[0.98, 83.12], P=0.05). The associations between renal vascular lesions, renal outcomes, and death were not significant, likely because of insufficient power. Conclusions Renal vascular lesions are common in SLE patients with nephritis and may be associated with arterial vascular events. PMID:22442181

  18. [A comparative study of the activity of a natural peptide complex in the kidneys and its synthetic analogs in autoimmune nephritis].

    PubMed

    Geĭko, O A; Bobrova, N A; Kaĭdashev, I P

    1998-01-01

    The activity of the natural peptide complex of the kidneys and of its synthetic analogs (PEKDLRK, PEKDSRK, PEKDDRL) in autoimmune nephritis was studied on golden hamsters. All the peptides under study demonstrated therapeutic activity but were characterized by peculiarity of their effect. The peptide PEKDLRK possessed the most marked capacity for stimulating phagocytic reactions, PEKDDRL apparently activated the system of natural killers. It is concluded that the study of peptides-analogs as potential drugs is promising. PMID:9783109

  19. Granulomatous interstitial nephritis and Crohn's disease.

    PubMed

    Timmermans, Sjoerd A M E G; Christiaans, Maarten H L; Abdul-Hamid, Myrurgia A; Stifft, Frank; Damoiseaux, Jan G M C; van Paassen, Pieter

    2016-08-01

    Granulomatous interstitial nephritis has been observed in <1% of native renal biopsies. Here, we describe two patients with granulomatous interstitial nephritis in relation to Crohn's disease. Circulating helper and cytotoxic T cells were highly activated, and both cell types predominated in the interstitial infiltrate, indicating a cellular autoimmune response. After immunosuppressive treatment, renal function either improved or stabilized in both patients. In conclusion, granulomatous interstitial nephritis is a genuine extraintestinal manifestation of Crohn's disease, the treatment of which should include immunosuppressive agents. PMID:27478596

  20. Opposing Roles of Tyrosine Kinase Receptors Mer and Axl Determine Clinical Outcomes in Experimental Immune-Mediated Nephritis.

    PubMed

    Zhen, Yuxuan; Priest, Stephen O; Shao, Wen-Hai

    2016-09-15

    Glomerulonephritis is one of the most severe manifestations of systemic lupus erythematosus, with considerable morbidity and mortality. There remains a major unmet need for successful management of lupus nephritis. TAM family receptor tyrosine kinases (Mer and Axl) play an important role in the maintenance of immune homeostasis in the kidney. Mer is constitutively expressed in the glomeruli; Axl expression is inducible in glomeruli under inflammatory conditions. To investigate the distinct functions of Axl and Mer in lupus nephritis, we compared the severity of nephrotoxic serum glomerulonephritis in wild-type (WT), Axl-knockout (KO), Mer-KO, and Axl/Mer-KO mice. Mer-KO mice developed severe glomerulonephritis, with significantly decreased survival and increased blood urea nitrogen levels compared with WT mice given the same treatment. However, nephrotoxic serum-treated Axl-KO mice had significantly increased survival rates and improved renal function compared with similarly treated WT, Mer-KO, and Axl/Mer-KO mice. Interestingly, mice lacking both Axl and Mer developed kidney inflammation comparable to WT mice. Western blot analysis revealed significantly increased Stat3 phosphorylation and caspase-1 activation in the kidneys of nephritic Mer-KO mice. In contrast, Axl-deficient nephrotoxic serum-injected mice showed decreased Akt phosphorylation and Bcl-xL upregulation. Thus, the reciprocal activation of Axl and Mer receptor tyrosine kinases has a major impact on the outcome of renal inflammation. PMID:27527599

  1. Quercitrin ameliorates the development of systemic lupus erythematosus-like disease in a chronic graft-versus-host murine model.

    PubMed

    Li, Wei; Li, Hu; Zhang, Mu; Wang, Mengqi; Zhong, Youxiu; Wu, Hezhen; Yang, Yanfang; Morel, Laurence; Wei, Qun

    2016-07-01

    Systemic lupus erythematosus (SLE) is a serious disorder of immune regulation characterized by overproduction of autoantibodies, lupus nephritis, CD4+ T cell aberrant activation, and immune complex-mediated inflammation. The chronic graft vs. host disease (cGVHD) mouse model is a well-established model of SLE. Quercitrin is a natural compound found in Tartary buckwheat with a potential anti-inflammatory effect that is used to treat heart and vascular conditions. In our previous study, we determined that quercitrin is an immunosuppressant with beneficial effects in mouse models of immune diseases. We hypothesized that quercitrin could prevent lupus nephritis in the cGVHD mouse model by decreasing the production of autoantibodies and inflammatory cytokines, and reducing immune cell activation. cGVHD was induced by injecting DBA/2 spleen cells into the tail vein of BDF1 mice. The cGVHD mice exhibited significant proteinuria, which is a marker of nephritis. Quercitrin decreased the number of serum antibodies, CD4+ T cell activation, as well as the expression levels of T-bet, GATA-3, and selected cytokines. Moreover, quercitrin treatment decreased the expression of inflammatory genes and cytokines in the kidney, as well as in peritoneal macrophages. In addition, quercitrin inhibited LPS-induced cytokines as well as the phosphorylation of ERK, p38 MAPK, and JNK in Raw264.7 cells. Overall, quercitrin ameliorated the symptoms of lupus nephritis in the cGVHD mouse model, which may be due to the inhibition of CD4 T cell activation and anti-inflammatory effects on macrophages. PMID:26911849

  2. Shared signaling networks active in B cells isolated from genetically distinct mouse models of lupus

    PubMed Central

    Wu, Tianfu; Qin, Xiangmei; Kurepa, Zoran; Kumar, Kirthi Raman; Liu, Kui; Kanta, Hasna; Zhou, Xin J.; Satterthwaite, Anne B.; Davis, Laurie S.; Mohan, Chandra

    2007-01-01

    Though B cells play key roles in lupus pathogenesis, the molecular circuitry and its dysregulation in these cells as disease evolves remain poorly understood. To address this, a comprehensive scan of multiple signaling axes using multiplexed Western blotting was undertaken in several different murine lupus strains. PI3K/AKT/mTOR (mTOR, mammalian target of rapamycin), MEK1/Erk1/2, p38, NF-κB, multiple Bcl-2 family members, and cell-cycle molecules were observed to be hyperexpressed in lupus B cells in an age-dependent and lupus susceptibility gene–dose–dependent manner. Therapeutic targeting of the AKT/mTOR axis using a rapamycin (sirolimus) derivative ameliorated the serological, cellular, and pathological phenotypes associated with lupus. Surprisingly, the targeting of this axis was associated with the crippling of several other signaling axes. These studies reveal that lupus pathogenesis is contingent upon the activation of an elaborate network of signaling cascades that is shared among genetically distinct mouse models and raise hope that targeting pivotal nodes in these networks may offer therapeutic benefit. PMID:17641780

  3. What Is Lupus?

    MedlinePlus

    ... better about themselves Remain more active. Pregnancy and Contraception for Women With Lupus Women with lupus can ... harmful to an unborn baby may want reliable birth control. Recent studies have shown that oral contraceptives (birth ...

  4. Macrophage depletion ameliorates nephritis induced by pathogenic antibodies.

    PubMed

    Chalmers, Samantha A; Chitu, Violeta; Herlitz, Leal C; Sahu, Ranjit; Stanley, E Richard; Putterman, Chaim

    2015-02-01

    Kidney involvement affects 40-60% of patients with lupus, and is responsible for significant morbidity and mortality. Using depletion approaches, several studies have suggested that macrophages may play a key role in the pathogenesis of lupus nephritis. However, "off target" effects of macrophage depletion, such as altered hematopoiesis or enhanced autoantibody production, impeded the determination of a conclusive relationship. In this study, we investigated the role of macrophages in mice receiving rabbit anti-glomerular antibodies, or nephrotoxic serum (NTS), an experimental model which closely mimics the immune complex mediated disease seen in murine and human lupus nephritis. GW2580, a selective inhibitor of the colony stimulating factor-1 (CSF-1) receptor kinase, was used for macrophage depletion. We found that GW2580-treated, NTS challenged mice did not develop the increased levels of proteinuria, serum creatinine, and BUN seen in control-treated, NTS challenged mice. NTS challenged mice exhibited significantly increased kidney expression of inflammatory cytokines including RANTES, IP-10, VCAM-1 and iNOS, whereas GW2580-treated mice were protected from the robust expression of these inflammatory cytokines that are associated with lupus nephritis. Quantification of macrophage related gene expression, flow cytometry analysis of kidney single cell suspensions, and immunofluorescence staining confirmed the depletion of macrophages in GW2580-treated mice, specifically within renal glomeruli. Our results strongly implicate a specific and necessary role for macrophages in the development of immune glomerulonephritis mediated by pathogenic antibodies, and support the development of macrophage targeting approaches for the treatment of lupus nephritis. PMID:25554644

  5. Towards new avenues in the management of lupus glomerulonephritis.

    PubMed

    Mok, C C

    2016-04-01

    Renal involvement in systemic lupus erythematosus (SLE) carries substantial morbidity and mortality. Conventional immunosuppressive agents (cyclophosphamide and azathioprine) have suboptimal efficacy and substantial toxicity. Mycophenolate mofetil has emerged as an alternative agent for both induction and maintenance therapy in lupus nephritis because of its reduced gonadal toxicity, despite its failure to demonstrate superiority over cyclophosphamide in pivotal studies. The calcineurin inhibitor tacrolimus has equivalent efficacy to cyclophosphamide and mycophenolate mofetil for inducing remission of lupus nephritis. Although rituximab has shown promise in refractory lupus nephritis, combining rituximab with mycophenolate mofetil as initial therapy offers no additional benefit. Considerable interethnic variation is evident in the efficacy and tolerability of the various immunosuppressive regimens, which necessitates individualized treatment and comparison of the efficacy of new regimens across different ethnic groups. For example, low-dose combinations of tacrolimus and mycophenolate mofetil seem to be more effective than pulse cyclophosphamide as induction therapy in Chinese patients. The same regimen has also been used successfully to treat refractory proliferative and membranous lupus nephritis in patients of various ethnic groups. Finally, novel serum and urinary biomarkers are being validated for diagnosis, prognostic stratification and early recognition of flares in lupus nephritis. PMID:26729459

  6. Lupus - resources

    MedlinePlus

    Resources - lupus ... The following organizations are good resources for information on systemic lupus erythematosus : The Lupus Foundation of America -- www.lupus.org The National Institute of Arthritis and Musculoskeletal ...

  7. Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model.

    PubMed

    Botte, D A C; Noronha, I L; Malheiros, D M A C; Peixoto, T V; de Mello, S B V

    2014-08-01

    Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option. PMID:24666423

  8. Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model

    PubMed Central

    Botte, D A C; Noronha, I L; Malheiros, D M A C; Peixoto, T V; de Mello, S B V

    2014-01-01

    Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP–MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP–MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option. PMID:24666423

  9. 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

  10. Development and management of systemic lupus erythematosus in an HIV-infected man with hepatitis C and B co-infection following interferon therapy: a case report

    PubMed Central

    2009-01-01

    Introduction The association of human immunodeficiency virus and immune dysfunction leading to development of autoimmune markers is well described, but human immunodeficiency virus infection is relatively protective for the development of systemic lupus erythematosus. In contrast, development of systemic lupus erythematosus with hepatitis C and with interferon therapy is well described in a number of case reports. We here describe the first case of systemic lupus erythematosus developing in a man infected with human immunodeficiency virus, hepatitis C and hepatitis B co-infection where the onset seems to have been temporally related to interferon therapy. Case presentation We report the occurrence of systemic lupus erythematosus complicating interferon-α therapy for hepatitis C in a 47-year-old asplenic male with haemophilia co-infected with human immunodeficiency virus and hepatitis B. He presented with a truncal rash, abdominal pains and headache and later developed grade IV lupus nephritis requiring haemodialysis, mycophenolate mofetil and steroid therapy. We were able to successfully withdraw dialysis and mycophenolate while maintaining stable renal function. Conclusion Interferon-α is critical in antiviral immunity against hepatitis C but also acts as a pathogenic mediator for systemic lupus erythematosus, a condition associated with activation of plasmacytoid dendritic cells that are depleted in human immunodeficiency virus infection. The occurrence of auto-antibodies and lupus-like features in the coinfections with hepatitis C require careful assessment. Immunosuppressant therapy for lupus risks exacerbating underlying infections in patients with concurrent human immunodeficiency virus, hepatitis B and C. PMID:19830165

  11. Systemic Lupus Erythematosus Presenting as Neuroretinitis.

    PubMed

    Santra, Gouranga; Das, Indrani

    2015-10-01

    Neuroretinitis is the inflammation of retina and optic nerve. It is associated with optic disc edema accompanied by peripapillary or macular hard exudates. A 17 yr old female presented with headache and nausea of five days duration. She had periorbital edema and mild splenomegaly. Neurological assessment was non-contributory. She was found to have pancytopenia, albuminuria and a high ESR. Thereafter she developed blurring of vision of both eyes. Opthalmological examination showed it to be due to bilateral neuroretinitis. ANA and anti-ds DNA were strongly positive. Renal biopsy with immunofluorescence study revealed diffuse global proliferative lupus nephritis with active lesions [class IV-G (A)]. She was diagnosed as a case of SLE presenting with neuroretinitis. PMID:27608700

  12. Radiation nephritis causing nephrotic syndrome

    SciTech Connect

    Jennette, J.C.; Ordonez, N.G.

    1983-12-01

    Clinical symptoms of acute radiation nephritis with nephrotic syndrome developed in a fifty-six-year-old woman after abdominal radiation therapy for an astrocytoma of the spinal cord. The diagnosis of radiation nephritis was confirmed by renal biopsy. To our knowledge, this is the first documented case of radiation nephritis associated with nephrotic syndrome.

  13. Caspase-Activated DNase is Required to Maintain Tolerance to Lupus Nuclear AutoAntigens

    PubMed Central

    Jog, Neelakshi R.; Frisoni, Lorenza; Shi, Qin; Monestier, Marc; Hernandez, Sairy; Craft, Joe; Luning Prak, Eline T.; Caricchio, Roberto

    2011-01-01

    Objective Caspase Activated DNase (CAD) is an endonuclease that is activated by active caspase 3 during apoptosis and is responsible for degradation of chromatin into nucleosomal units. These nucleosomal units are then included in apoptotic bodies. The presence of apoptotic bodies is considered important for the generation of auto-antigens in autoimmune diseases such as lupus, which are characterized by the presence of anti-nuclear antibodies. Methods The present study was carried out to determine the role of CAD in Sle1, Sle123 and 3H9 spontaneous models of lupus, where autoimmunity is genetically pre-determined. We also determined the ability of lupus auto-antibodies to bind to CAD deficient or sufficient apoptotic cells. Results The deficiency of CAD resulted in higher anti-dsDNA antibody titers in lupus-prone mice. Surprisingly, the absence of CAD only exacerbated genetically pre-determined autoimmune responses. To further determine whether nuclear modifications are required to maintain tolerance to nuclear auto-antigens, we used the 3H9 mouse, an anti-DNA heavy chain knock-in. In this model, the autoreactive B cells are tolerized by anergy. In line with the Sle1 and Sle123 CAD mutant mice, CAD deficient 3H9 mice spontaneously generated anti-DNA antibodies. We finally show that auto-antibodies with specificities towards histone/DNA complexes bind more to CAD deficient apoptotic cells compared to CAD sufficient apoptotic cells. Conclusions We propose that in mice genetically predisposed to lupus, nuclear apoptotic modifications are required to maintain tolerance. In the absence of these modifications, apoptotic chromatin is abnormally exposed, facilitating the autoimmune response. PMID:22127758

  14. Anti-C1q in systemic lupus erythematosus.

    PubMed

    Stojan, G; Petri, M

    2016-07-01

    C1q is the first component of the classical complement pathway. Both clinically validated in-house ELISA assays as well as commercial ELISA kits are used for detection of anti-C1q antibodies. Anti-C1q autoantibodies can be detected in a wide range of autoimmune diseases and are highly sensitive for hypocomplementemic uticarial vasculitis. In SLE, anti-C1q are strongly associated with proliferative lupus nephritis, and their absence carries a negative predictive value for development of lupus nephritis of close to 100%. Anti-C1q in combination with anti-dsDNA and low complement has the strongest serological association with renal involvement. The anti-C1q titers correlate with global disease activity scores in patients with renal involvement, and higher titers seem to precede renal flares. After the successful treatment of a renal flare, anti-C1q has the tendency to decrease or even become undetectable. The main obstacle to the inclusion of anti-C1q in the classification criteria and clinical management of SLE is the lack of standardized laboratory assays. PMID:27252264

  15. Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients

    PubMed Central

    Tokutake, Takayoshi; Baba, Hisami; Shimada, Yuji; Takeda, Wataru; Sato, Keijiro; Hiroshima, Yuki; Kirihara, Takehiko; Shimizu, Ikuo; Nakazawa, Hideyuki; Kobayashi, Hikaru; Ishida, Fumihiro

    2016-01-01

    The activated partial thromboplastin time (APTT) assay is a basic hemostatic assay based on the time it takes for clots to form in plasma samples after the addition of calcium chloride. It is used to screen for various coagulation disorders. Several previous reports have suggested that magnesium (Mg) might contribute to coagulation reactions by binding to specific coagulation proteins. We investigated the effects of Mg on the APTT. In healthy controls, the APTT was significantly prolonged in proportion to the increase in the concentration of magnesium chloride in the range from 2.1 to 16.7 mmol/L. Among eight samples from patients with various disorders that exhibited prolonged APTT, two samples demonstrated shorter APTT when Mg was added, both of which were from patients that were positive for lupus anticoagulant. When we examined 206 clinical APTT samples, we found that Mg shortened the APTT of two samples. These two samples were also from lupus anticoagulant-positive patients (p-value: <0.003). Our findings regarding the unique effects of exogenous Mg on the APTT of lupus anticoagulant-positive patients might shed light on the role of Mg in APTT assays and lead to the development of a novel screening method for lupus anticoagulant. PMID:27355205

  16. Extragonadal germ cell tumor presenting in a woman with systemic lupus erythematosus: a case report

    PubMed Central

    2010-01-01

    Introduction Germ cell tumor of the pituitary gland is a very rare occurrence. Case presentation We describe the case of a 28-year-old Malaysian Malay woman with lupus nephritis who complained of a three month headache and blurring of vision. She was found to have a pituitary mass, which was later proven to be a germ cell tumor. As of writing this case report, her disease is in remission. Conclusion The disruption of the pituitary gonad axis could affect the disease activity by reducing immunoregulatory control. PMID:20338049

  17. Macrophage depletion ameliorates nephritis induced by pathogenic antibodies

    PubMed Central

    Chalmers, Samantha A.; Chitu, Violeta; Herlitz, Leal C.; Sahu, Ranjit; Stanley, E. Richard; Putterman, Chaim

    2014-01-01

    Objective Kidney involvement affects 40–60% of patients with lupus and is responsible for significant morbidity and mortality. Using depletion approaches, several studies have suggested that macrophages may play a key role in the pathogenesis of lupus nephritis. However, “off target” effects of macrophage depletion, such as altered hematopoiesis or enhanced autoantibody production, impeded the determination of a conclusive relationship. Methods In this study, we investigated the role of macrophages in mice receiving rabbit anti-glomerular antibodies, or nephrotoxic serum (NTS), an experimental model which closely mimics the immune complex mediated disease seen in murine and human lupus nephritis. GW2580, a selective inhibitor of the colony stimulating factor-1 (CSF-1) receptor kinase, was used for macrophage depletion. Results We found that GW2580-treated, NTS challenged mice did not develop the increased levels of proteinuria, serum creatinine, or serum urea seen in control-treated, NTS challenged mice. NTS challenged mice exhibited significantly increased kidney expression of inflammatory cytokines including RANTES, IP-10, VCAM-1 and iNOS, whereas GW2580-treated mice were protected from the robust expression of these inflammatory cytokines that are associated with LN. Quantification of macrophage related gene expression, flow cytometry analysis of kidney single cell suspensions, and immunofluorescence staining confirmed the depletion of macrophages in GW2580-treated mice, specifically within renal glomeruli. Conclusions Our results strongly implicate a specific and necessary role for macrophages in the development of immune glomerulonephritis mediated by pathogenic antibodies, and support the development of macrophage targeting approaches for the treatment of lupus nephritis. PMID:25554644

  18. Pregnancy-related issues in women with systemic lupus erythematosus.

    PubMed

    Singh, Abha G; Chowdhary, Vaidehi R

    2015-02-01

    While fertility is preserved in females with systemic lupus erythematosus (SLE), it is well established that pregnancy in these patients is associated with adverse maternal and fetal outcomes, including pregnancy loss, pre-eclampsia, preterm delivery and intrauterine growth retardation, as well as neonatal mortality. Mechanisms underlying these adverse outcomes are poorly understood, and better understanding of these would allow development of targeted and personalized treatment strategies. Established risk factors for adverse pregnancy outcomes include active disease within 6 months prior to conception and during pregnancy, active nephritis, maternal hypertension, antiphospholipid antibodies and hypocomplementemia. While intensive monitoring is recommended, the comparative effectiveness of appropriate management strategies is unclear. While current strategies are able to achieve live births in 85-90% of pregnancies, certain aspects such as prevention of preterm birth, treatment of congenital heart block due to neonatal lupus and recurrent pregnancy loss despite best management, remains challenging. Pregnancy is also associated with an increased risk of flare of lupus, particularly in patients with active disease at time of conception or within 6 months prior to conception. Pregnant patients with SLE should be followed in a high-risk obstetric clinic, and care should be closely coordinated between the obstetrician and rheumatologist. PMID:25545844

  19. [Treatment of systemic lupus erythematosus: myths, certainties and doubts].

    PubMed

    Ruiz-Irastorza, Guillermo; Danza, Alvaro; Khamashta, Munther

    2013-12-21

    Systemic lupus erythematosus (SLE) is a complex disease with different clinical forms of presentation, including a wide range of severity and organic involvement. Such circumstance, along with the fact of the uncommon nature of the disease and the absence of clinically representative response criteria, make it difficult to design controlled clinical trials in SLE patients. As a result, observational studies have a special relevance, being a source of valuable information of SLE prognosis and outcome as well as of the efficacy and adverse effects of the different therapies. Herein we update some of the main treatments used in SLE. Steroids may have more risks than benefits if used at high doses. New mechanisms of action have been described, supporting the use of lower doses, possibly with the same efficacy and less adverse effects. Intravenous pulses of cyclophosphamide still have a role in the treatment of proliferative lupus nephritis and other serious SLE manifestations. Mycophenolate mofetil has shown its efficacy both as induction and maintenance therapy of selected cases of lupus nephritis. Biological therapies have emerged as new promising options. Although clinical trials have not confirmed a clear superiority of rituximab in SLE, observational studies have shown good response rates in severe SLE manifestations or refractory forms. Belimumab has recently been added to the therapeutic armamentarium of SLE; although its place in clinical practice is not well-defined, it may be recommended in active patients with no response or good tolerance to standard therapies. Hydroxichloroquine improves survival, decreases the risk of thrombosis and flares and is safe in pregnancy, and should be considered the baseline therapy in most SLE patients. PMID:23622892

  20. Study of circulating immune complex size in systemic lupus erythematosus.

    PubMed Central

    Tung, K S; DeHoratius, R J; Williams, R C

    1981-01-01

    The molecular size of circulating immune complexes in patients with systemic lupus erythematosus was determined by the C1q solid-phase assay after the sera were fractionated by sucrose-gradient ultracentrifugation. Circulating immune complexes in patients with membranous glomerulonephritis were uniformly large, sedimenting exclusively above 19S, whereas the immune complexes in patients with cerebritis were small, at or just above 7S. In lupus patients with diffuse proliferative glomerulonephritis and patients without renal involvement, immune complexes of both large and small sizes were found. Of patients without renal involvement, more circulating immune complexes were associated with active disease (n = 22, prevalence = 82%, mean level = 24 standard deviations) than with inactive disease (n = 17, prevalence = 41%, mean level = 41%, mean level = 6 . 5 standard deviations). In patients with clinical evidence for renal involvement, circulating immune complexes were detected in all of five patients with membranous glomerulonephritis, in 88% of 17 patients with diffuse proliferative glomerulonephritis and in one of four patients with mesangial nephritis. Thus, in addition to the finding of an overall positive correlation between disease activity and circulating immune complex levels, circulating immune complexes of certain general molecular size ranges appear to be associated with different clinical manifestations of systemic lupus erythematosus. Images Fig. 1 Fig. 2 Fig. 3 PMID:7285395

  1. Refractory disease in systemic lupus erythematosus.

    PubMed

    Campar, Ana; Farinha, Fátima; Vasconcelos, Carlos

    2011-09-01

    There is no definition or guidelines for refractory disease (RD) in Systemic Lupus Erythematosus (SLE). However, new therapies have been tested mainly in refractory patients. The concept, like the disease, is complex and implies deeper knowledge on the disease pathogenesis and patients' subsets. RD is not included in current activity indices of the disease, what raises the question of how are we monitoring its response to new drugs. In this paper, we analyse some concepts considered important for the global definition of RD in SLE and in some specific organ involvements, excluding lupus nephritis. Management issues will be addressed also. Finally, we review therapeutic options in particular subsets of the disease, namely, cutaneous, articular, haematological and neuropsychiatric lupus. Crucial to the management of a patient suspected to be refractory is an accurate diagnosis, assuring that the persistent clinical manifestations are derived primarily from SLE and not from a concomitant or alternative process. Likewise, certainty about the patient compliance with the therapy prescribed is a frequent unrecognized problem that erroneously might lead to a classification of RD. Therapy of RD for SLE, in general and in most particular involvements, is currently based mainly on the clinician's own experience and judgement, with few randomized trials effectively addressing the issue. In such a heterogeneous disease, consideration of approval of drugs for single-organ indications may pave the way for new therapies. Better biomarkers are needed to add accuracy to the currently used activity indices in order to monitor RD and consolidate its definition. Prospective studies directed to RD in the main SLE involvements are needed to improve our understanding on the management of the disease and foster the development of targeted new drugs. PMID:21600313

  2. Karyomegalic Interstitial Nephritis

    PubMed Central

    Isnard, Pierre; Rabant, Marion; Labaye, Jacques; Antignac, Corinne; Knebelmann, Bertrand; Zaidan, Mohamad

    2016-01-01

    Abstract Karyomegalic interstitial nephritis is a rare cause of hereditary chronic interstitial nephritis, described for the first time over 40 years ago. A 36-year-old woman, of Turkish origin, presented with chronic kidney disease and high blood pressure. She had a history of recurrent upper respiratory tract infections but no familial history of nephropathy. Physical examination was unremarkable. Laboratory tests showed serum creatinine at 2.3 mg/dL with an estimated glomerular filtration rate of 26 mL/min/1.73m2, and gamma-glutamyl transpeptidase and alkaline phosphatase at 3 and 1.5 times the upper normal limit. Urinalysis showed 0.8 g/day of nonselective proteinuria, microscopic hematuria, and aseptic leukocyturia. Immunological tests and tests for human immunodeficiency and hepatitis B and C viruses were negative. Complement level and serum proteins electrophoresis were normal. Analysis of the renal biopsy showed severe interstitial fibrosis and tubular atrophy. Numerous tubular cells had nuclear enlargement with irregular outlines, hyperchromatic aspect, and prominent nucleoli. These findings were highly suggestive of karyomegalic interstitial nephritis, which was further confirmed by exome sequencing of FAN1 gene showing an identified homozygous frameshift mutation due to a one-base-pair deletion in exon 12 (c.2616delA). The present case illustrates a rare but severe cause of hereditary interstitial nephritis, sometimes accompanied by subtle extrarenal manifestations. Identification of mutations in FAN1 gene underscores recent insights linking inadequate DNA repair and susceptibility to chronic kidney disease. PMID:27196444

  3. NF-κB and systemic lupus erythematosus: examining the link.

    PubMed

    Zubair, Adeel; Frieri, Marianne

    2013-01-01

    Physicians should be knowledgeable regarding several aspects of autoimmune disorders, especially systemic lupus erythematosus (SLE), with which patients can present in their office with urticaria or vasculitis and which may masquerade as another condition. This paper reviews the link between NF-κB and SLE, including B-cell development, signaling and cytokines which play a crucial role in the pathogenesis of SLE and T-cell development, a key player in T-cell activation. The roles of dendritic cells, which can promote tolerance or immunity to antigens, of polymorphisms and of NF-κB, which are linked with SLE, are also discussed. The role of Toll-like receptors which are important in the pathogenesis of SLE and lupus nephritis is also discussed. PMID:23807646

  4. 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

  5. T-cell-directed therapies in systemic lupus erythematosus.

    PubMed

    Nandkumar, P; Furie, R

    2016-09-01

    Drug development for the treatment of systemic lupus erythematosus (SLE) has largely focused on B-cell therapies. A greater understanding of the immunopathogenesis of SLE coupled with advanced bioengineering has allowed for clinical trials centered on other targets for SLE therapy. The authors discuss the benefits and shortcomings of focusing on T-cell-directed therapies in SLE and lupus nephritis clinical trials. PMID:27497252

  6. 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

  7. Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus—An Immunological Dilemma

    PubMed Central

    Velciov, Silvia; Gluhovschi, Adrian

    2015-01-01

    Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE) is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg) cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth) or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis) may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother's disease, is required. It is important to understand immune tolerance to grafts in transplant pathology. PMID:26090485

  8. Macrophage activation syndrome as the initial manifestation of severe juvenile onset systemic lupus erythematosus. Favorable response to cyclophosphamide.

    PubMed

    Torres Jiménez, Alfonso; Solís Vallejo, Eunice; Zeferino Cruz, Maritza; Céspedes Cruz, Adriana; Sánchez Jara, Berenice

    2014-01-01

    The macrophage activation syndrome is a rare but potentially fatal complication of patients with autoimmune rheumatic diseases. This is a clinicopathological entity characterized by activation of histiocytes with prominent hemophagocytosis in the bone marrow and other reticuloendothelial systems. In patients with lupus it may mimic an exacerbation of the disease or infection. We report the case of a 7-year-old girl in whom the diagnosis of lupus erythematosus and macrophage activation syndrome was simultaneously made with response to the use of cyclophosphamide. PMID:24035795

  9. 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

  10. 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

  11. Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus.

    PubMed

    Monteith, Andrew J; Kang, SunAh; Scott, Eric; Hillman, Kai; Rajfur, Zenon; Jacobson, Ken; Costello, M Joseph; Vilen, Barbara J

    2016-04-12

    Defects in clearing apoptotic debris disrupt tissue and immunological homeostasis, leading to autoimmune and inflammatory diseases. Herein, we report that macrophages from lupus-prone MRL/lpr mice have impaired lysosomal maturation, resulting in heightened ROS production and attenuated lysosomal acidification. Impaired lysosomal maturation diminishes the ability of lysosomes to degrade apoptotic debris contained within IgG-immune complexes (IgG-ICs) and promotes recycling and the accumulation of nuclear self-antigens at the membrane 72 h after internalization. Diminished degradation of IgG-ICs prolongs the intracellular residency of nucleic acids, leading to the activation of Toll-like receptors. It also promotes phagosomal membrane permeabilization, allowing dsDNA and IgG to leak into the cytosol and activate AIM2 and TRIM21. Collectively, these events promote the accumulation of nuclear antigens and activate innate sensors that drive IFNα production and heightened cell death. These data identify a previously unidentified defect in lysosomal maturation that provides a mechanism for the chronic activation of intracellular innate sensors in systemic lupus erythematosus. PMID:27035940

  12. IL-33 neutralization suppresses lupus disease in lupus-prone mice.

    PubMed

    Li, Pin; Lin, Wei; Zheng, Xiangxiong

    2014-06-01

    IL-33 is a new member of the IL-1 family that plays a role in inflammation. In this study, we evaluated the potential of IL-33 inhibition as a treatment for systemic lupus erythematosus (SLE) using the lupus-prone model MRL/lpr mice and the underlying mechanisms of action. We treated mice with anti-mouse IL-33 antibody (anti-IL-33Ab) via intraperitoneal injection every other day from week 14 until week 20 for 6 weeks. A control group received the same amount of IgG control. Renal damage and mouse survival were compared. Cytokines, antibodies, immune complex, Tregs, myeloid-derived suppressor cells (MDSCs), and Th17 cells were also analyzed. Correlations between serum IL-33 and SLE disease activity index in human SLE were also investigated. MRL/lpr mice treated with anti-IL-33Ab showed reduced proteinuria and reduced serum anti-dsDNA levels. Nephritis, immune complex deposits, and the circulating antibodies and immune complex besides the mortality were significantly reduced by anti-IL-33Ab. Anti-IL-33Ab remarkably increased Tregs and MDSCs and reduced the Th17 cells and IL-1β, IL-6, and IL-17 levels in MRL/lpr mice. These results suggest that IL-33 inhibition may inhibit SLE via expansion of Tregs and MDSCs and inhibition of Th17 cells and proinflammatory responses, indicating that blockade of IL-33 has a protective effect on SLE. PMID:24398614

  13. Neutrophil Extracellular Trap-Associated Protein Activation of the NLRP3 Inflammasome Is Enhanced in Lupus Macrophages

    PubMed Central

    Kahlenberg, J. Michelle; Carmona-Rivera, Carmelo; Smith, Carolyne K.; Kaplan, Mariana J.

    2012-01-01

    Neutrophil extracellular traps (NETs) represent an important defense mechanism against microorganisms. Clearance of NETs is impaired in a subset of patients with systemic lupus erythematosus (SLE), while NETosis is increased in neutrophils and, particularly, in low-density granulocytes derived from lupus patients. NETs are toxic to the endothelium, expose immunostimulatory molecules, activate plasmacytoid dendritic cells and may participate in organ damage through incompletely characterized pathways. In order to better understand the role of NETs in fostering dysregulated inflammation, we examined inflammasome activation in response to NETs or to LL-37, an antibacterial protein externalized on the NETs. Both NETs and LL-37 activate caspase-1, the central enzyme of the inflammasome, in both human and murine macrophages, resulting in release of active IL-1β and IL-18. LL-37 activation of the NLRP3 inflammasome utilizes P2×7 receptor-mediated potassium efflux. NET and LL-37-mediated activation of the inflammasome is enhanced in macrophages derived from lupus patients. In turn, IL-18 is able to stimulate NETosis in human neutrophils. These results suggest that enhanced formation of NETs in lupus patients can lead to increased inflammasome activation in adjacent macrophages. This leads to release of inflammatory cytokines which further stimulate NETosis, resulting in a feed-forward inflammatory loop that could potentially lead to disease flares and/or organ damage. PMID:23267025

  14. Granulomatous interstitial nephritis

    PubMed Central

    Shah, Shivani; Carter-Monroe, Naima; Atta, Mohamed G.

    2015-01-01

    Granulomatous interstitial nephritis (GIN) is a rare entity detected in ∼0.5–0.9% of all renal biopsies. GIN has been linked to several antibiotics such as cephalosporins, vancomycin, nitrofurantoin and ciprofloxacin. It is also associated with NSAIDs and granulomatous disorders such as sarcoidosis, tuberculosis, fungal infections, and granulomatosis with polyangiitis. Renal biopsy is critical in establishing this diagnosis, and the extent of tubular atrophy and interstitial fibrosis may aid in determining prognosis. Retrospective data and clinical experience suggest that removal of the offending agent in conjunction with corticosteroid therapy often results in improvement in renal function. We describe a patient with a history of multiple spinal surgeries complicated by wound infection who presented with confusion and rash with subsequent development of acute kidney injury. Urinalysis demonstrated pyuria and eosinophiluria, and renal biopsy revealed acute interstitial nephritis with granulomas. These findings were attributed to doxycycline treatment of his wound infection. This review explores the clinical associations, presentation, diagnosis, and treatment of this uncommon cause of acute kidney injury. PMID:26413275

  15. Granulomatous interstitial nephritis.

    PubMed

    Shah, Shivani; Carter-Monroe, Naima; Atta, Mohamed G

    2015-10-01

    Granulomatous interstitial nephritis (GIN) is a rare entity detected in ∼0.5-0.9% of all renal biopsies. GIN has been linked to several antibiotics such as cephalosporins, vancomycin, nitrofurantoin and ciprofloxacin. It is also associated with NSAIDs and granulomatous disorders such as sarcoidosis, tuberculosis, fungal infections, and granulomatosis with polyangiitis. Renal biopsy is critical in establishing this diagnosis, and the extent of tubular atrophy and interstitial fibrosis may aid in determining prognosis. Retrospective data and clinical experience suggest that removal of the offending agent in conjunction with corticosteroid therapy often results in improvement in renal function. We describe a patient with a history of multiple spinal surgeries complicated by wound infection who presented with confusion and rash with subsequent development of acute kidney injury. Urinalysis demonstrated pyuria and eosinophiluria, and renal biopsy revealed acute interstitial nephritis with granulomas. These findings were attributed to doxycycline treatment of his wound infection. This review explores the clinical associations, presentation, diagnosis, and treatment of this uncommon cause of acute kidney injury. PMID:26413275

  16. Self-reported and Objectively Measured Physical Activity in Adults with Systemic Lupus Erythematosus

    PubMed Central

    Ahn, Grace E.; Chmiel, Joan S.; Dunlop, Dorothy D.; Helenowski, Irene; Semanik, Pamela A.; Song, Jing; Ainsworth, Barbara; Chang, Rowland W.; Ramsey-Goldman, Rosalind

    2014-01-01

    Objective Most estimates of physical activity (PA) patterns in systemic lupus erythematosus (SLE) are based on subjective self-report measures prone to error. The aims of this study were to obtain objective measurements of PA using an accelerometer and estimates of energy expenditure based on the self-reported International Physical Activity Questionnaire (IPAQ), and to describe their relationship. Methods The “Activity in Lupus To Energize and Renew” (ALTER) study, a cross-sectional study of PA, included 129 persons with SLE. Accelerometer measures over 7 days included total daily activity counts and minutes of moderate-vigorous physical activity (MVPA). Each person completed the IPAQ via telephone interview. Spearman correlations (r) and 95% confidence intervals (CIs) assessed associations between accelerometer and IPAQ. Results Daily PA means (SD) from accelerometer measures were total daily activity counts, 502,910 (118,755) and MVPA, 40 (30) minutes. The median (interquartile range) MET-min per day for IPAQ intensities were: total 400 (159–693); walking, 83 (26–184); and moderate-vigorous, 231 (77–514), and domains were: work 0 (0–73); active transportation 28 (0–85); domestic and garden 77 (26–231); and leisure 57 (0–213). Associations between accelerometer measures and IPAQ were: 1) total daily count vs. IPAQ total, r=0.21, 95% CI: (0.03, 0.37); and 2) MVPA vs. IPAQ moderate-vigorous, r=0.16, 95% CI: (-0.02, 0.33). Conclusion Accelerometer measures and IPAQ energy expenditure estimates were moderately correlated. IPAQ provided descriptive PA data whereas accelerometers captured all daily activities and can help assess guideline attainment. The choice of IPAQ versus accelerometer measure should consider the purpose for which PA is measured. PMID:25251755

  17. Systemic lupus erythematosus and atherosclerosis: Review of the literature.

    PubMed

    Frieri, Marianne; Stampfl, Heather

    2016-01-01

    The purpose of this manuscript is to extensively review the literature related to systemic lupus erythematosus and atherosclerosis. The conclusion of this review has covered accelerated atherosclerosis in systemic lupus erythematosus, the role of complement, interferon in premature atherosclerosis, inflammatory mediators such as cytokines, leukocytes, innate and adaptive immunity, hydrolytic enzymes, reactive oxygen species, vascular endothelial growth factor, toll receptors in lupus nephritis, several specific anti-inflammatory pharmacological therapies, and potential prevention strategies for atherothrombotic events, interferons and the inflammasome. It is important for allergist-immunologists, rheumatologists both in academic institutions and in practice to understand this important disorder. PMID:26299985

  18. 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

  19. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

    PubMed

    Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

    2015-05-01

    In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

  20. Has the diversity of clinical and biological manifestations of systemic lupus erythematosus a correspondent in the diversity of immune mechanisms? Observations based on a Rowell's syndrome case associated with arthritis and nephritis.

    PubMed

    Gluhovschi, Gh; Trandafirescu, V; Solovan, C; Lazăr, E; Gluhovschi, Cristina; Petrica, Ligia; Bob, F; Bozdog, Gh; Gadalean, F; Cornianu, M; Velciov, Silvia

    2012-01-01

    This paper draws attention to the relationship between the clinical and biological picture of SLE and the immune mechanisms of this disease. The presence, in the same patient, of erythema multiforme-like skin lesions and erythemato-squamous lesions specific for SLE together with a characteristic immune picture (speckled antinuclear antibodies (ANAs), positive anti-Ro antibodies, positive rheumatoid factor) raise the question of a relationship between the immune mechanisms in SLE and the clinical picture. A case of Rowell's syndrome is discussed: systemic lupus erythematosus diagnosed on the occasion of an erythema multiforme-like rash. Starting from this case, we analyse if the clinical and biological picture in SLE is an expression of the immune mechanisms involved in this disease. Our patient presented with speckled antinuclear antibodies, positive rheumatoid factor, anti-Ro antibodies, suggestive of Rowell's syndrome. The patient manifested rheumatoid-like articular pain and high titer rheumatoid factor. Clinically, we found erythema multiforme-like and erythemato-squamous lesions. The patient developed nephrotic syndrome (proteinuria 11.8g/24h), and renal failure (creatinine 3.08 mg/dl). The renal biopsy showed mesangial proliferative glomerulonephritis class II (ISN/RPS). Under treatment with prednisone the nephrotic syndrome evolved into remission (traces of proteinuria) and serum creatinine declined (1.03 mg/dl). The cutaneous syndrome had a spectacular evolution, too. The question is raised of the existence in Rowell's syndrome of immune mechanisms commonly encountered in SLE and a subset associated with the cutaneous erythema multiforme-like rash and pseudo-rheumatoid arthritis manifestations. PMID:23330294

  1. 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

  2. Dehydroepiandrosterone in systemic lupus erythematosus

    PubMed Central

    Sawalha, Amr H; Kovats, Susan

    2009-01-01

    Dehydroepiandrosterone (DHEA) is a weak androgen that exerts pleomorphic effects on the immune system. The hormone has no known receptor, and consequently, the mechanism of action of DHEA on immunocompetent cells remains poorly understood. Interestingly, serum levels of DHEA are decreased in patients with inflammatory disease including lupus, and these levels seem to inversely correlate with disease activity. Following encouraging studies demonstrating beneficial effects of DHEA supplementation in murine lupus models, a number of clinical studies have tested the effect of DHEA administration in lupus patients. DHEA treatment could improve patient’s overall quality of life assessment measures and glucocorticoid requirements in some lupus patients with mild to moderate disease, however, the effect of DHEA on disease activity in lupus patients remains controversial. Long term safety assessment studies are required in light of the reported effect of DHEA supplementation in lowering HDL cholesterol in lupus patients. PMID:18662508

  3. Pre-B cell leukemia homeobox 1 is associated with lupus susceptibility in mice and humans

    PubMed Central

    Cuda, Carla M.; Li, Shiwu; Liang, Shujuan; Yin, Yiming; Potula, Hari Hara S.K.; Xu, Zhiwei; Sengupta, Mayami; Chen, Yifang; Butfiloski, Edward; Baker, Henry; Chang, Lung-Ji; Dozmorov, Igor; Sobel, Eric S.; Morel, Laurence

    2011-01-01

    Sle1a.1 is part of the Sle1 susceptibility locus, which has the strongest association with lupus nephritis in the NZM2410 mouse model. Here we show that Sle1a.1 results in the production of activated and autoreactive CD4+ T cells. In addition, Sle1a.1 expression reduces the peripheral regulatory T cell (Treg) pool, as well as induces a defective response of CD4+ T cells to the retinoic acid (RA) expansion of TGFβ-induced Tregs. At the molecular level, Sle1a.1 corresponds to an increased expression of a novel splice isoform of Pbx1, Pbx1-d. Pbx1-d over-expression is sufficient to induce an activated/inflammatory phenotype in Jurkat T cells, and to decrease their apoptotic response to RA. PBX1-d is expressed more frequently in the CD4+ T cells from lupus patients than from healthy controls, and its presence correlates with an increased central memory T cell population. These findings indicate that Pbx1 is a novel lupus susceptibility gene that regulates T cell activation and tolerance. PMID:22180614

  4. [Genetics of lupus erythematosus].

    PubMed

    Günther, Claudia

    2015-02-01

    Lupus erythematosus is a prototypic autoimmune disease that can be triggered in genetically predisposed individuals by environmental exposures. The disease is based on an uncontrolled activation of the immune system that recognizes self antigens and induces inflammatory disease flares. The multifactorial pathogenesis is based on a polygenic model of inheritance with multiple various susceptibility genes elevating the disease risk. Many of these polymorphisms have been recently identified by genome-wide association studies. Monogenic forms of lupus erythematosus are rare. The identification of their underlying pathogenesis is important for the recognition of main mechanistic pathways in lupus as demonstrated by the history of defects in the complement system. The monogenic, autosomal dominant inherited familial chilblain lupus is characterized by cold-induced infiltrates on acral locations occurring in early childhood. Molecular exploration of the disease pathogenesis revealed that autoimmunity and especially lupus erythematosus can be induced by defects in intracellular elimination of nucleic acids and the subsequent type I-IFN-dependent activation of the innate immune system. This mechanism extends the concept of lupus pathogenesis: both defects in the extra- and intracellular elimination of autoantigens can lead to activation of the innate and adaptive immune system. PMID:25659384

  5. Acute tubulointerstitial nephritis.

    PubMed

    Ulinski, Tim; Sellier-Leclerc, Anne-Laure; Tudorache, Elena; Bensman, Albert; Aoun, Bilal

    2012-07-01

    Acute tubulointerstitial nephritis (TIN) is a frequent cause of acute renal failure, characterised by the presence of inflammatory cell infiltrate in the interstitium of the kidney. Immuno-allergic reaction to certain medications, mainly non-steroidal anti-inflammatory drugs and antibiotics are by far the most important etiology for TIN today, but other situations such as infections, toxins, and vasculitis are known to induce TIN. Incidence of TIN is increasing, probably due to prescription habits and NSAID overuse, representing 3-7% of acute kidney injury in biopsies in children. Avoidance of the causal substance and rapid steroid therapy are hallmarks for patient care, but spontaneous initial recovery is very frequent and the general prognosis seems satisfactory. However, development of chronic TIN, without response to steroid or other immunosuppressive treatment, is possible. As the largest part of TIN is secondary to certain drugs, clear indications in particular for NSAID or antibiotics should be respected to reduce the number of TIN cases. PMID:21638156

  6. 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

  7. Alternative therapies: what role do they have in the management of lupus?

    PubMed

    Chou, C-T

    2010-10-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease with higher morbidity and mortality among ethnic Chinese patients than Whites. Corticosteroid and other immunosuppressive drugs, including cyclophosphamide, azathioprine, and hydroxychloroquine are traditional therapies for this disease. Since the year 2000, mycophenolate mofetil and rituximab have been widely used in refractory SLE or severe lupus nephritis. Because the high disease activity remains, even after active therapy, and serious side effects from Western medicines may develop, more than 40% of SLE patients in Western countries are pursuing complementary and alternative therapies (CATs). CAT remedies are multiplex, and include herbal medicines, diets and vitamins, acupuncture, chiropractice, folk medicine, massage, spiritual healing, etc. Many herbal formulas have been used but in general their efficacy in treating lupus is doubted because of the lack of strong evidence. Tripterygium (T2) has demonstrated good efficacy in rheumatoid arthritis (RA) and SLE, but widespread use is limited due to the side effects. Through randomized clinical trials, we hope in the future that some Chinese medicines may be found helpful as CATs for SLE. PMID:20947552

  8. [Age and the course of nephrotoxic nephritis in rats].

    PubMed

    Samoĭlova, Z T; Kliukina, S S

    1978-12-01

    In experiments on two groups of mongrel rats (4 weeks old and 4 months old) with induced nephrotoxic nephritis it was revealed that in comparison with adult rats the course of nephritis in ratlings was characterized by lesser proteinuria, selective in nature, by lesser reducticn of endogenous creatinine clearance and diuresis. The acido- and ammo-niogenesis decreased in ratlings and adult rats to the same extent. Morphological changes in the kidneys of ratlings were less pronounced than in adult animals, and were mostly localized in the convoluted tubules. The level of DNA-synthetic activity of the epithelial nuclei of the glomeruli prevailed over this index of the convoluted tubules epithelium. The weight index of the kidneys increased less in ratlings with nephritis than in adult rats. beta-lipoproteinemia in ratlings increased 8 times. Normalization of the urine and blood indices occurred more rapidly in ratlings than in adult rats. PMID:31956

  9. 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

  10. 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

  11. 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

  12. 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

  13. Tubulointerstitial nephritis and uveitis: an immunological disorder?

    PubMed

    Birnbacher, R; Balzar, E; Aufricht, C; Schmaldienst, S; Woloszczuk, W; Förster, E

    1995-04-01

    A 14-year-old boy with tubulointerstitial nephritis and uveitis (TINU syndrome) is described. Nephropathy improved without systemic cortisone treatment, whereas uveitis relapsed and was treated with topical steroids. Blood cell immunological analysis and serum analysis revealed signs of cytotoxic T-cell, macrophage and granulocyte activation, which declined as the clinical symptoms improved. This may be interpreted as an indication of their significance as markers in the pathogenesis of this syndrome or as part of a microbial-triggered immune response. PMID:7794717

  14. Dynamics of mononuclear phagocyte system Fc receptor function in systemic lupus erythematosus. Relation to disease activity and circulating immune complexes.

    PubMed

    Kimberly, R P; Parris, T M; Inman, R D; McDougal, J S

    1983-02-01

    Seventeen pairs of longitudinal studies of mononuclear phagocyte system (MPS) Fc receptor function in 15 patients with systemic lupus were performed to explore the dynamic range of Fc receptor dysfunction in lupus and to establish the relationships between MPS function, clinical disease activity and circulating immune complexes (CIC). Fc receptor function was measured by the clearance of IgG sensitized autologous erythrocytes. At the time of first study the degree of MPS dysfunction was correlated with both clinical activity (P less than 0.05) and CIC (P less than 0.05). At follow-up patients with a change in clinical status show significantly larger changes in clearance function compared to clinically stable patients (206 min vs 7 min; P less than 0.001). MPS function changed concordantly with a change in clinical status in all cases (P = 0.002). Longitudinal assessments did not demonstrate concordance of changes in MPS function and CIC, measured by three different assays. The MPS Fc receptor defect in systemic lupus is dynamic and closely associated with disease activity. The lack of concordance of the defect with changes in CIC suggests that either CIC does not adequately reflect receptor site saturation or that other factors may also contribute to the magnitude of MPS dysfunction. PMID:6839542

  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. 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

  17. Efficacy of plasma exchange and immunoadsorption in systemic lupus erythematosus and antiphospholipid syndrome: A systematic review.

    PubMed

    Kronbichler, Andreas; Brezina, Biljana; Quintana, Luis F; Jayne, David R W

    2016-01-01

    Extracorporeal treatments have been used since the 1970s in the management of systemic lupus erythematosus (SLE). A randomised controlled trial comparing the efficacy of standard of care (SOC) combined with plasma exchange against SOC alone in patients with lupus nephritis revealed no difference in terms of renal outcome. Subsequently, initial expectations have been dampened and further experience with plasma exchange is mainly limited to observational studies and single case reports. Beneficial effects have been reported in patients with refractory disease course or in pregnancy with prior complications due to SLE and antiphospholipid syndrome. A more specific form of extracorporeal treatment, immunoadsorption (IAS), has emerged as a valuable option in the treatment of SLE. In line with the plasma exchange experience, IAS seems to have beneficial effects in patients with refractory disease, contraindications to standard immunosuppression or during pregnancy. The mechanism IAS relates to autoantibody removal but for plasma exchange removal of activated complement components, coagulation factors, cytokines and microparticles may also be relevant. Both treatment forms have good safety profiles although reactions to blood product replacement in plasma exchange and procedure related complications such as bleeding or catheter-related infections have occurred. There is a need to more clearly define the clinical utility of plasma exchange and IAS in refractory lupus and APS subgroups. PMID:26318215

  18. 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

  19. Systemic lupus erythematosus

    MedlinePlus

    Disseminated lupus erythematosus; SLE; Lupus; Lupus erythematosus; Butterfly rash-SLE; Discoid lupus ... Mouth sores. Sensitivity to sunlight. Skin rash: A "butterfly" rash in about half the people with SLE. ...

  20. 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

  1. 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

  2. Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study.

    PubMed

    Wu, Tianfu; Ding, Huihua; Han, Jie; Arriens, Cristina; Wei, Chungwen; Han, Weilu; Pedroza, Claudia; Jiang, Shan; Anolik, Jennifer; Petri, Michelle; Sanz, Ignacio; Saxena, Ramesh; Mohan, Chandra

    2016-07-01

    A discovery study was carried out where serum samples from 22 systemic lupus erythematosus (SLE) patients and matched healthy controls were hybridized to antibody-coated glass slide arrays that interrogated the level of 274 human proteins. On the basis of these screens, 48 proteins were selected for ELISA-based validation in an independent cohort of 28 SLE patients. Whereas AXL, ferritin, and sTNFRII were significantly elevated in patients with active lupus nephritis (LN) relative to SLE patients who were quiescent, other molecules such as OPN, sTNFRI, sTNFRII, IGFBP2, SIGLEC5, FAS, and MMP10 exhibited the capacity to distinguish SLE from healthy controls with ROC AUC exceeding 90%, all with p < 0.001 significance. These serum markers were next tested in a cohort of 45 LN patients, where serum was obtained at the time of renal biopsy. In these patients, sTNFRII exhibited the strongest correlation with eGFR (r = -0.50, p = 0.0014) and serum creatinine (r = 0.57, p = 0.0001), although AXL, FAS, and IGFBP2 also correlated with these clinical measures of renal function. When concurrent renal biopsies from these patients were examined, serum FAS, IGFBP2, and TNFRII showed significant positive correlations with renal pathology activity index, while sTNFRII displayed the highest correlation with concurrently scored renal pathology chronicity index (r = 0.57, p = 0.001). Finally, in a longitudinal cohort of seven SLE patients examined at ∼3 month intervals, AXL, ICAM-1, IGFBP2, SIGLEC5, sTNFRII, and VCAM-1 demonstrated the ability to track with concurrent disease flare, with significant subject to subject variation. In summary, serum proteins have the capacity to identify patients with active nephritis, flares, and renal pathology activity or chronicity changes, although larger longitudinal cohort studies are warranted. PMID:27211902

  3. B7x/B7-H4 modulates the adaptive immune response and ameliorates renal injury in antibody-mediated nephritis

    PubMed Central

    Pawar, R D; Goilav, B; Xia, Y; Herlitz, L; Doerner, J; Chalmers, S; Ghosh, K; Zang, X; Putterman, C

    2015-01-01

    Kidney disease is one of the leading causes of death in patients with lupus and other autoimmune diseases affecting the kidney, and is associated with deposition of antibodies as well as infiltration of T lymphocytes and macrophages, which are responsible for initiation and/or exacerbation of inflammation and tissue injury. Current treatment options have relatively limited efficacy; therefore, novel targets need to be explored. The co-inhibitory molecule, B7x, a new member of the B7 family expressed predominantly by non-lymphoid tissues, has been shown to inhibit the proliferation, activation and functional responses of CD4 and CD8 T cells. In this study, we found that B7x was expressed by intrinsic renal cells, and was up-regulated upon stimulation with inflammatory triggers. After passive administration of antibodies against glomerular antigens, B7x−/− mice developed severe renal injury accompanied by a robust adaptive immune response and kidney up-regulation of inflammatory mediators, as well as local infiltration of T cells and macrophages. Furthermore, macrophages in the spleen of B7x−/− mice were polarized to an inflammatory phenotype. Finally, treatment with B7x-immunoglobulin (Ig) in this nephritis model decreased kidney damage and reduced local inflammation. We propose that B7x can modulate kidney damage in autoimmune diseases including lupus nephritis and anti-glomerular basement membrane disease. Thus, B7x mimetics may be a novel therapeutic option for treatment of immune-mediated kidney disease. PMID:25205493

  4. Treating Lupus

    MedlinePlus

    ... Awards Investigator Grants, Fellowships and Career Development Awards & Prizes Peer-Reviewed Grant Program LIFELINE Grant Program 2015 ... Postal Code: Spam Control Text: Please leave this field empty Get social Facebook Twitter Instgram Lupus.org ...

  5. Animal Models of Interferon Signature Positive Lupus.

    PubMed

    Zhuang, Haoyang; Szeto, Christopher; Han, Shuhong; Yang, Lijun; Reeves, Westley H

    2015-01-01

    Human lupus is strongly associated with a gene expression signature characterized by over-expression of Type I interferon-regulated genes. A strong interferon signature generally is not seen in the standard mouse models of lupus, despite considerable evidence for the involvement of toll-like receptor-driven interferon production. In contrast, pristane-induced lupus exhibits a prominent TLR7-dependent interferon signature. Importantly, genetic disorders with dysregulated interferon production in both human beings and mice cause severe autoinflammatory diseases but not the typical manifestations of lupus, suggesting that interferon over-production is insufficient to cause systemic lupus erythematosus itself. Single-gene models in mice suggest that lupus-like disease may result from abnormalities in B-cell activation and the clearance of dead cells. Pristane may mimic human systemic lupus erythematosus by causing synergistic abnormalities in interferon production along with defective clearance of apoptotic cells and over-active B-cell signaling. PMID:26097482

  6. Animal Models of Interferon Signature Positive Lupus

    PubMed Central

    Zhuang, Haoyang; Szeto, Christopher; Han, Shuhong; Yang, Lijun; Reeves, Westley H.

    2015-01-01

    Human lupus is strongly associated with a gene expression signature characterized by over-expression of Type I interferon-regulated genes. A strong interferon signature generally is not seen in the standard mouse models of lupus, despite considerable evidence for the involvement of toll-like receptor-driven interferon production. In contrast, pristane-induced lupus exhibits a prominent TLR7-dependent interferon signature. Importantly, genetic disorders with dysregulated interferon production in both human beings and mice cause severe autoinflammatory diseases but not the typical manifestations of lupus, suggesting that interferon over-production is insufficient to cause systemic lupus erythematosus itself. Single-gene models in mice suggest that lupus-like disease may result from abnormalities in B-cell activation and the clearance of dead cells. Pristane may mimic human systemic lupus erythematosus by causing synergistic abnormalities in interferon production along with defective clearance of apoptotic cells and over-active B-cell signaling. PMID:26097482

  7. Blockade of CD354 (TREM-1) Ameliorates Anti-GBM-Induced Nephritis.

    PubMed

    Du, Yong; Wu, Tianfu; Zhou, Xin J; Davis, Laurie S; Mohan, Chandra

    2016-06-01

    CD354, Triggering Receptor of Myeloid Cells-1 (TREM-1), is a potent amplifier of myeloid immune responses. Our goal was to determine the expression and function of TREM-1 in immune-mediated nephritis. An anti-glomerular basement membrane antibody (anti-GBM)-induced nephritis model was employed, where mice were sensitized with rabbit IgG followed by anti-GBM serum to induce disease. Anti-GBM-treated 129x1/svJ mice developed severe nephritis whereas C57BL/6 (B6) mice were resistant to disease. Anti-GBM disease resulted in elevated renal TREM-1 messenger RNA (mRNA) and protein levels and increased urine TREM-1 levels in 129x1/svJ. TREM-1 blockade with an inhibitory peptide, LP17, inhibited proteinuria and renal disease as measured by glomerulonephritis class, severity of tubulointerstitial disease, crescent formation, and inflammatory cell infiltrates. In sum, TREM-1 is upregulated in renal inflammation and plays a vital role in driving disease. Thus, TREM-1 blockade emerges as a potential therapeutic avenue for immune-mediated renal diseases such as lupus nephritis. PMID:27083877

  8. Suspected ciprofloxacin-induced interstitial nephritis.

    PubMed

    Murray, K M; Wilson, M G

    1990-04-01

    Interstitial nephritis is a rare but serious adverse effect of many drugs and usually is diagnosed by clinical signs and symptoms of hematuria, proteinuria, eosinophilia, fever, azotemia, and rash. Ciprofloxacin is one drug that has been reported to cause interstitial nephritis. Renal toxicities have been reported in less than one percent of the patients receiving ciprofloxacin therapy. Limited documentation of this adverse effect exists in the literature. This article describes a patient with suspected ciprofloxacin-induced interstitial nephritis. PMID:2327115

  9. Role of abnormal anterior pituitary hormones-growth hormone and prolactin in active systemic lupus erythematosus

    PubMed Central

    Zhu, Xiaohua; Xu, Jinhua; Li, Shujuan; Huang, Wen; Li, Feng

    2015-01-01

    Background: The role of anterior pituitary hormones in systemic lupus erythematosus (SLE) remains controversial. Aims and Objectives: We determined the expression levels of human growth hormone (GH), prolactin (PRL), and their receptors in subjects presenting with SLE, and modulation of disease severity. Materials and methods: Forty-seven subjects and ten healthy controls were assessed for possible association between SLE disease activity and levels of serum PRL, GH and thyrotropin-releasing hormone (TRH). In peripheral blood mononuclear cells (PBMC), specific binding and mRNA expression of receptors for GH (GHR), and PRL (PRLR) were determined by receptor-ligand binding assay (RLBA) and RT-PCR. PBMC of recruited subjects were treated with hPRL and rhGH to assess IgG production and antibodies against dsDNA. Results: In active SLE subjects we found elevated PRL and GH levels. Study subject PBMCs displayed augmented GHR and PRLR protein and mRNA expression. Study subjects also showed a positive correlation in serum PRL levels and specific antibodies against dsDNA, SLE disease activity index (SLEDAI), and proteinuria. However, a negative correlation was found between serum PRL levels and complement component C3. We found a positive correlation between specific binding rates of PRLR and GHR and both SLE activity and dsDNA antibody titers. Enhanced IgG and anti-dsDNA secretion was observed in cultured PBMC stimulated by PRL or GH with/without PHA, PWM, IL-2 or IL-10. In active SLE, a close association was found between augmented PRL and GH levels, expression and specific binding activities of PRLR and GHR, and changes in the specific titer of anti-dsDNA. Conclusion: Anterior pituitary hormones play an important role in the pathogenesis of SLE. High levels of growth hormone (GH) and prolactin (PRL) play a role in pathogenesis of SLE, which is correlated with SLE disease activity and antibodies against dsDNA. The mechanism of GH and PRL in SLE was complicated and should

  10. Adalimumab (TNFα Inhibitor) Therapy Exacerbates IgA Glomerulonephritis Acute Renal Injury and Induces Lupus Autoantibodies in a Psoriasis Patient

    PubMed Central

    Wei, S. S.; Sinniah, R.

    2013-01-01

    Adalimumab (Humira) is a tumour necrosis factor α (TNFα) inhibitor that is approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ankylosing spondylitis, and juvenile idiopathic arthritis (Sullivan and Preda (2009), Klinkhoff (2004), and Medicare Australia). Use of TNFα inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, and sarcoidosis or sarcoid-like granulomas) (Ramos-Casals et al. (2010)). We report a patient with extensive psoriasis presenting with renal failure and seropositive lupus markers without classical lupus nephritis after 18 months treatment with adalimumab. He has renal biopsy proven IgA nephritis instead. Renal biopsy is the key diagnostic tool in patients presenting with adalimumab induced nephritis and renal failure. He made a remarkable recovery after adalimumab cessation and steroid treatment. To our knowledge, this is a unique case of a psoriasis patient presenting with seropositive lupus markers without classical lupus nephritis renal failure and had renal biopsy proven IgA glomerulonephritis after receiving adalimumab. PMID:24558628

  11. Systemic lupus erythematosus in Nepal: A review.

    PubMed

    Kafle, M P; Lee, Vws

    2016-08-01

    Nepal is a small country that is landlocked between India and China. Several ethnic groups live within the 147,181 km(2) of this country. Geographic diversity ranges from the high Himalayas to the flatlands of the Ganges plains. Lupus nephritis (LN), a complication of systemic lupus erythematosus (SLE), is a common kidney problem in Nepal; but the real incidence and prevalence of SLE in Nepal is largely not known. Here, it more commonly affects people (mostly women) living in the southern flatlands, but SLE is reported to be uncommon further south in India. Even though the disease appears to be common, good quality research is uncommon in Nepali literature. This article was written to provide a review of the articles published to date about SLE in Nepal and to discuss the gaps in knowledge that require further evaluation. PMID:26957353

  12. Biomarkers for kidney involvement in pediatric lupus

    PubMed Central

    Goilav, Beatrice; Putterman, Chaim; Rubinstein, Tamar B

    2015-01-01

    Lupus nephritis (LN), the renal involvement in systemic lupus erythematosus, is currently diagnosed by histopathology obtained by percutaneous renal biopsy and is associated with increased morbidity and mortality in both adults and children. LN is more prevalent and severe in children, requiring aggressive and prolonged immunosuppression. The consequences of the diagnosis and its treatment have devastating long-term effects on the growth, well-being and quality of life of affected children. The paucity of reliable clinical indicators of the presence and severity of renal involvement have contributed to a halt in the reduction of progression to end-stage renal disease in recent years. Here, we discuss the recent development of biomarkers in the management of LN and their role as therapeutic targets. PMID:26079958

  13. CXCR5 is critically involved in progression of lupus through regulation of B cell and double-negative T cell trafficking.

    PubMed

    Wiener, A; Schippers, A; Wagner, N; Tacke, F; Ostendorf, T; Honke, N; Tenbrock, K; Ohl, K

    2016-07-01

    The recruitment of immune cells to sites of tissue inflammation is orchestrated by chemokine/chemokine receptor networks. Among these, the CXCL13/CXCR5 axis is thought to be involved critically in systemic lupus erythematosus (SLE) and lupus nephritis pathogenesis. Beyond B cell abnormalities, another hallmark of SLE disease is the occurrence of aberrant T cell responses. In particular, double-negative (DN) T cells are expanded in the peripheral blood of patients with SLE and in lupus-prone mice. DN T cells induce immunoglobulin production, secrete proinflammatory cytokines and infiltrate inflamed tissue, including kidneys. We aimed to investigate how CXCR5 deficiency changes immune cell trafficking in murine lupus. We therefore crossed CXCR5(-/-) mice with B6/lpr mice, a well-established murine lupus model. B cell numbers and B cellular immune responses were diminished in CXCR5-deficient B6/lpr mice. In addition, we observed reduced accumulation of DN T cells in spleen and lymph nodes, paralleled by reduced splenomegaly and lymphadenopathy. In-vivo migration assays revealed reduced migration of CXCR5-deficient DN T cells into lymph nodes, and ex-vivo-activated CXCR5-deficient DN T cells failed to infiltrate kidneys of recipients. Moreover, DN T cells and B cells of CXCR5-deficient B6/lpr mice failed to migrate towards CXCL13 in vitro. We propose that CXCR5 is involved critically in B cell trafficking and germinal cell (GC) formation in murine lupus and in guiding pathogenic DN T cells into lymphoid organs and kidneys, and we therefore describe new pathomechanisms for the CXCL13/CXCR5 axis in SLE. PMID:26990531

  14. 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

  15. 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

  16. [Progress and perspectives in the treatment of systemic lupus erythematosus].

    PubMed

    Robak, Ewa; Sysa-Jedrzejowska, Anna; Wozniacka, Anna

    2005-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women in childbearing age. SLE tissue damage is mediated by autoantibodies, complement activation and immune complexes deposition. The disease is diagnosed on the basis of its clinical manifestations and the demonstration of characteristic immunological phenomena, especially antinuclear antibodies. Management of the disease includes regular monitoring of disease activity, avoidance of predisposing factors and therapy guided by the activity and severity of the leading organ manifestation. Treatment ranges from nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents. Corticosteroids form the basis of all regimens. Antimalarials and azathioprine are important for treating mild and moderate SLE cases, especially for the long time. Cyclophosphamide given intravenously is the current gold standard for severe lupus nephritis. More recently new strategies for immunosuppression in SLE, that interfere with the syntesis of DNA and nucleotides have been developed (such as mycophenolate mofetil, fludarabine and cladribine). Other agents like cyclosporine and tacrolimus inhibit effect of the activation signals for T cells by inhibition of calcineurin. Some monoclonal antibodies against cytokines or components of the complement system interfere with the effector phase of the immune response. Abetimus (LJP-394) inhibits the production of anti-dsDNA antibodies and may prevent glomerulonephritis caused by anti-DNA containing immune complexes. Somatic gene therapy is also a novel approach in autoimmune disorders and my be a valuable method of SLE therapy in the future. The adrenal steroid prasterone (DHEA) has also shown benefitial effects in mild to moderate SLE. Finally, autologous stem cell transplantation can induce tolerance to self-antigens and cause significant improvement in SLE patients. However, new therapeutic strategies must be tested according to the established

  17. High-mobility Group Box-1 Protein Promotes Granulomatous Nephritis in Adenine-induced nephropathy

    PubMed Central

    Oyama, Yoko; Hashiguchi, Teruto; Taniguchi, Noboru; Tancharoen, Salunya; Uchimura, Tomonori; Biswas, Kamal K.; Kawahara, Ko-ichi; Nitanda, Takao; Umekita, Yoshihisa; Lotz, Martin; Maruyama, Ikuro

    2011-01-01

    Granulomatous nephritis can be triggered by diverse factors and results in kidney failure. However, despite accumulating data about granulomatous inflammation, pathogenetic mechanisms in nephritis remain unclear. The DNA-binding high-mobility group box-1 protein (HMGB1) initiates and propagates inflammation when released by activated macrophages, functions as an “alarm cytokine” signaling tissue damage. In this study, we demonstrated elevated HMGB1 expression in renal granulomas in rats with crystal-induced granulomatous nephritis caused by feeding an adenine-rich diet. HMGB1 levels were also raised in urine and serum, as well as monocyte chemoattractant protein-1 (MCP-1), a mediator of granulomatous inflammation. Injection of HMGB1 worsened renal function and upregulated MCP-1 in rats with crystal-induced granulomatous nephritis. HMGB1 also induced MCP-1 secretion through mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) pathways in rat renal tubular epithelial cells in vitro. Hmgb1+/− mice with crystal-induced nephritis displayed reduced MCP-1 expression in the kidneys and in urine and the number of macrophages in the kidneys was significantly decreased. We conclude that HMGB1 is a new mediator involved in crystal-induced nephritis that amplifies granulomatous inflammation in a cycle where MCP-1 attracts activated macrophages, resulting in excessive and sustained HMGB1 release. HMGB1 could be a novel target for inhibiting chronic granulomatous diseases. PMID:20231821

  18. Polyomavirus-associated nephritis in 2 horses.

    PubMed

    Jennings, S H; Wise, A G; Nickeleit, V; Maes, R K; Cianciolo, R E; Del Piero, F; Law, J M; Kim, Y; McCalla, A C; Breuhaus, B A; Roberts, M C; Linder, K E

    2013-09-01

    Polyomaviruses produce latent and asymptomatic infections in many species, but productive and lytic infections are rare. In immunocompromised humans, polyomaviruses can cause tubulointerstitial nephritis, demyelination, or meningoencephalitis in the central nervous system and interstitial pneumonia. This report describes 2 Standardbred horses with tubular necrosis and tubulointerstitial nephritis associated with productive equine polyomavirus infection that resembles BK polyomavirus nephropathy in immunocompromised humans. PMID:23381926

  19. Epratuzumab for systemic lupus erythematosus.

    PubMed

    Wallace, D J; Goldenberg, D M

    2013-04-01

    Epratuzumab (EMab, UCB, Immunomedics) is a humanized monoclonal antibody targeting CD22 that is being studied in clinical trials for patients with a variety of rheumatic and hematologic conditions, including systemic lupus erythematosus (SLE). An overview of its mechanism of action is followed by a summary of completed lupus studies, and a preview of studies in progress. The agent clearly has anti-inflammatory activity and is a potentially useful agent in the management of autoimmune disorders. PMID:23553783

  20. Refractory Angioedema in a Patient with Systemic Lupus Erythematosus

    PubMed Central

    Habibagahi, Zahra; Ruzbeh, Jamshid; Yarmohammadi, Vahide; Kamali, Malihe; Rastegar, Mohammad Hassan

    2015-01-01

    Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis. PMID:26170526

  1. 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

  2. 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

  3. Sildenafil Induced Acute Interstitial Nephritis

    PubMed Central

    Burkhart, Ryan; Shah, Nina; Lewin, Matthew

    2015-01-01

    Acute interstitial nephritis (AIN) is characterized by inflammation of the renal interstitium and usually occurs in a temporal relationship with the medication. We present a case of an Asian male who had nephrotic range proteinuria and presented with acute kidney injury. The patient reported an acute change in physical appearance and symptomatology after the ingestion of a single dose of sildenafil. Renal biopsy was notable for minimal change disease (MCD) with acute and chronic interstitial nephritis. Renal replacement and glucocorticoid therapy were initiated. Renal recovery within six weeks permitted discontinuation of dialysis. AIN superimposed on MCD is a known association of NSAID induced nephropathy. The temporal association and the absence of any new drugs suggest that the AIN was most likely due to the sildenafil. NSAIDs are less likely to have caused the AIN given their remote use. The ease of steroid responsiveness would also suggest another cause as NSAID induced AIN is often steroid resistant. The MCD was most likely idiopathic given the lack of temporal association with a secondary cause. As the number of sildenafil prescriptions increases, more cases of AIN may be identified and physician awareness for this potential drug disease association is necessary. PMID:26491581

  4. 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

  5. Systemic lupus erythematosus.

    PubMed

    Manson, Jessica J; Rahman, Anisur

    2006-01-01

    Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens. It is a multi-system disease, and patients can present in vastly different ways. Prevalence varies with ethnicity, but is estimated to be about 1 per 1000 overall with a female to male ratio of 10:1. The clinical heterogeneity of this disease mirrors its complex aetiopathogenesis, which highlights the importance of genetic factors and individual susceptibility to environmental factors. SLE can affect every organ in the body. The most common manifestations include rash, arthritis and fatigue. At the more severe end of the spectrum, SLE can cause nephritis, neurological problems, anaemia and thrombocytopaenia. Over 90% of patients with SLE have positive anti-nuclear antibodies (ANA). Significant titres are accepted to be of 1:80 or greater. SLE is a relapsing and remitting disease, and treatment aims are threefold: managing acute periods of potentially life-threatening ill health, minimizing the risk of flares during periods of relative stability, and controlling the less life-threatening, but often incapacitating day to day symptoms. Hydroxychloroquine and non-steroidal anti-inflammatory drugs are used for milder disease; corticosteroids and immunosuppressive therapies are generally reserved for major organ involvement; anti-CD20 monoclonal antibody is now used in patients with severe disease who has not responded to conventional treatments. Despite enormous improvements in prognosis since the introduction of corticosteroids and immunosuppressive drugs, SLE continues to have a significant impact on the mortality and morbidity of those affected. PMID:16722594

  6. 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

  7. An antibody profile of systemic lupus erythematosus detected by antigen microarray

    PubMed Central

    Fattal, Ittai; Shental, Noam; Mevorach, Dror; Anaya, Juan-Manuel; Livneh, Avi; Langevitz, Pnina; Zandman-Goddard, Gisele; Pauzner, Rachel; Lerner, Miriam; Blank, Miri; Hincapie, Maria-Eugenia; Gafter, Uzi; Naparstek, Yaakov; Shoenfeld, Yehuda; Domany, Eytan; Cohen, Irun R

    2010-01-01

    Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states – SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long-term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), Epstein–Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin-like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE. PMID:20201986

  8. 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

  9. Effect of total lymphoid irradiation on levels of serum autoantibodies in systemic lupus erythematosus and in rheumatoid arthritis

    SciTech Connect

    Tanay, A.; Schiffman, G.; Strober, S.

    1986-01-01

    The effects of total lymphoid irradiation (TLI) on serum levels of autoantibodies, and of antibodies to diphtheria toxoid, tetanus toxoid, and pneumococcal polysaccharide in patients with lupus nephritis were compared with those previously observed in rheumatoid arthritis (RA) patients. Baseline levels of antibodies to diphtheria toxoid and tetanus toxoid decreased significantly after TLI in patients with lupus and RA, but antibody levels to pneumococcal polysaccharide remained unchanged. After TLI, the levels of antinuclear and anti-DNA antibodies were reduced significantly in lupus, but levels of rheumatoid factor, antinuclear, and antigranulocyte antibodies all tended to increase in RA.

  10. Lupus erythematosus

    SciTech Connect

    Tuffanelli, D.L.

    1981-02-01

    Lupus erythematosus (LE) is a multisystem disease. Genetic predisposition, altered immunity, hormones, drugs, viruses, and ultraviolet light all may play a role in etiology. A wide range of cutaneous lesions occur, and variants such as subacute cutaneous LE, complement-deficient LE, and neonatal LE have recently been emphasized. Management of the LE patient, including appropriate diagnostic studies and therapy relevant to the dermatologist, is discussed in the review.

  11. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., however, absence of a kidney is the sole renal disability, even if removal was required because of nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in...

  12. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., however, absence of a kidney is the sole renal disability, even if removal was required because of nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in...

  13. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., however, absence of a kidney is the sole renal disability, even if removal was required because of nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in...

  14. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., however, absence of a kidney is the sole renal disability, even if removal was required because of nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in...

  15. 38 CFR 4.115 - Nephritis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., however, absence of a kidney is the sole renal disability, even if removal was required because of nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in...

  16. 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.

  17. 75 FR 35492 - Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus-Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    .... Specifically, the guidance addresses study population enrollment and efficacy endpoints for LN trials. In the Federal Register of March 29, 2005 (70 FR 15868), FDA announced the availability of a draft guidance..., efficacy endpoints, and response criteria in SLE. FDA received a number of comments on the draft...

  18. Poor agreement of objectively measured and self-reported physical activity in juvenile dermatomyositis and juvenile systemic lupus erythematosus.

    PubMed

    Pinto, Ana Jéssica; Roschel, Hamilton; Benatti, Fabiana Braga; de Sá Pinto, Ana Lúcia; Sallum, Adriana Maluf Elias; Silva, Clóvis Arthur; Gualano, Bruno

    2016-06-01

    To examine the agreement and association between objectively measured and indirectly assessed physical activity levels in patients with juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE) patients. The sample consisted of 19 JDM patients (age 8 to 22 years) and 20 JSLE patients (age 9 to 18 years). Physical activity level was objectively measured using Actigraph® accelerometers and indirectly assessed by the short-form International Physical Activity Questionnaire (IPAQ). Spearman's correlation coefficients were calculated to test possible associations between physical activity levels across the two instruments. The Bland-Altman technique was used to calculate bias and limits of agreement. Correlations between objectively measured and indirectly assessed physical activity levels in JDM and JSLE were weak, varying from R = 0.03 to R = 0.33 (all p > 0.05). Total physical activity was correlated between accelerometer and IPAQ in JSLE (R = 0.51, p = 0.021). Bland-Altman analyses suggested that IPAQ tended to highly underestimate sedentary time and light physical activity in JDM (mean bias 105.7 and 199.8 min, respectively) and JSLE (mean bias 36.4 and 127.8 min, respectively). Mean biases of moderate-to-vigorous physical activity were also highly variable, ranging from -42.9 to 54.9 min and -59.4 to 89.8 min for JDM and JSLE, respectively. IPAQ was shown to not be valid to assess physical activity levels in patients with JDM and JSLE when compared against accelerometry. While the validation of reliable self-reported instruments that measure physical activity in pediatric rheumatic patients remains necessary, the use of validated tools that objectively measure physical activity is recommended in both clinical and research settings. PMID:27021334

  19. 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

  20. 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

  1. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy.

    PubMed

    Blum, Daniel; Blake, Geoffrey

    2015-11-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady's TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  2. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

    PubMed Central

    Blum, Daniel; Blake, Geoffrey

    2015-01-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  3. Why are kids with lupus at an increased risk of cardiovascular disease?

    PubMed

    Quinlan, Catherine; Marks, Stephen D; Tullus, Kjell

    2016-06-01

    Juvenile-onset systemic lupus erythematosus (SLE) is an aggressive multisystem autoimmune disease. Despite improvements in outcomes for adult patients, children with SLE continue to have a lower life expectancy than adults with SLE, with more aggressive disease, a higher incidence of lupus nephritis and there is an emerging awareness of their increased risk of cardiovascular disease (CVD). In this review, we discuss the evidence for an increased risk of CVD in SLE, its pathogenesis, and the clinical approach to its management. PMID:26399239

  4. 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

  5. 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

  6. Radionuclide scintigraphy of bacterial nephritis

    SciTech Connect

    Conway, J.J.; Weiss, S.C.; Shkolnik, A.; Yogev, R.; Firlit, C.; Traisman, E.S.

    1984-01-01

    Pyelonephritis is a leading cause of renal failure and is expected to cost as much as three billion dollars in 1984. The diagnosis of urinary tract infection is usually not difficult. However, localization of the infection within the renal parenchyma as opposed to the collecting system is much more difficult. Flank pain, fever, bacteiuria and evidence of parenchymal involvement by intravenous urography may be absent or unrecognized particularly in the infant. Ultrasound and Nuclear Medicine are advocated as better methods to define parenchymal involvement. Such definition is important in the consideration of treatment since parenchymal involvement of the kidney carries a much more ominous potential outcome than infection restricted to within the collecting system. 38 children with a clinical diagnosis of urinary tract infection were studied. 26 of the patients demonstrated abnormal renal parenchymal findings with Gallium-67 Citrate or Tc-99m Glucoheptonate scintigraphy. Intravenous urography was notably ineffective with only 5 of the 20 interpreted as abnormal due to parenchymal disease or decreased function. 11 were entirely normal while only 5 demonstrated scars or hydronephrosis. Only 10 of 17 patients demonstrated intranvesicoureteral reflux on x-ray or nuclear cystography. Ultrasound depicted 6 of 20 patients as having parenchymal abnormalities. Seven were normal. Nonspecific findings such as dilitation of the renal pelvis or renal enlargement was noted in 11 of the 20 patients. Radionuclide Scintigraphy is the most efficacious modality to detect since acute bacterial nephritis.

  7. Junctional region sequences of T-cell receptor beta-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: possible selection by cationic autoantigens.

    PubMed Central

    Adams, S; Leblanc, P; Datta, S K

    1991-01-01

    We rescued from the spleens of 10 (SWR x NZB)F1 (SNF1) mice with lupus nephritis the T cells that were activated in vivo and cloned 268 T-cell lines and hybridomas. Only 12% of these T-cell clones had the functional ability to preferentially augment the production of pathogenic anti-DNA autoantibodies. Among these, 16 helper T-cell (Th-cell) clones that were mostly CD4+ and had the strongest autoantibody-inducing ability were analyzed for T-cell receptor (TCR) beta-chain gene usage. Seven of the 16 Th-cell clones expressed beta-chain variable region (V beta) V beta 8 (8.2 or 8.3) genes and three expressed V beta 4, whereas two clones each used a V beta 1 or V beta 2 or V beta 14 gene, suggesting some restriction in TCR gene usage. Although heterogeneous, the V-D-J junctional region sequences of TCR beta-chain genes used by these Th-cell clones invariably encoded one or more negatively charged residues (aspartic or glutamic acid) that had been generated in most cases by unspecified nucleotide (N) additions. Representative pathogenic autoantibody-inducing Th-cell clones could rapidly induce the development of lupus nephritis when injected into young prenephritic SNF1 mice. The pathogenic autoantibody-inducing Th cells expressing the anionic residues in their TCR beta-chain junctions (complementarity-determining region CDR3) were probably selected by some cationic autoantigenic peptide presented by the anti-DNA B cells they preferentially helped. These results offer a clue regarding the nature of the primary autoantigen that may drive the pathogenic autoimmune response in lupus. Images PMID:1837146

  8. Hypocomplementemic urticarial vasculitis or systemic lupus erythematosus?

    PubMed

    Trendelenburg, M; Courvoisier, S; Späth, P J; Moll, S; Mihatsch, M; Itin, P; Schifferli, J A

    1999-10-01

    The 2 patients presented here showed the typical signs of hypocomplementemic urticarial vasculitis syndrome (HUVS). During follow-up, there was an inverse correlation between anti-C1q autoantibody titer and C1q antigen concentration in serum in both patients over a period of 2 years. The first patient had nephritis characterized by immune deposits in glomeruli and around the tubules. The histological findings, C1q deposits, and presence of tubuloreticular inclusions in capillary endothelial cells suggested a disease process identical to systemic lupus erythematosus (SLE). The second patient, after a lag phase of 2 years, fulfilled a fourth American College of Rheumatology criteria for SLE when she developed anti-double-stranded DNA antibodies. HUVS and SLE overlap, and the criteria for identifying HUVS as an entity distinct from SLE are lacking. PMID:10516358

  9. Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus.

    PubMed

    Richards, H B; Satoh, M; Shaw, M; Libert, C; Poli, V; Reeves, W H

    1998-09-01

    Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6-deficient (-/-) and -intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, -double-stranded (ds)DNA, and -chromatin antibodies in IL-6(+/+), but not IL-6(-/-) mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not -/-, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6(-/-) and IL-6(+/+) mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses. PMID:9730900

  10. Psgl-1 Deficiency is Protective against Stroke in a Murine Model of Lupus.

    PubMed

    Wang, Hui; Knight, Jason S; Hodgin, Jeffrey B; Wang, Jintao; Guo, Chiao; Kleiman, Kyle; Eitzman, Daniel T

    2016-01-01

    Systemic lupus erythematosus (SLE) is associated with an elevated risk of vascular complications, including premature stroke. Therapies targeting leukocyte recruitment may be beneficial in reducing vascular complications associated with SLE. Lupus was induced in female wild-type (WT) and P-selectin glycoprotein ligand-1 deficient (Psgl-1(-/-)) mice with pristane. Stroke was induced following photochemical injury to the middle cerebral artery (MCA). Stroke size was increased in pristane-treated WT mice compared to non-pristane-treated WT controls. However, stroke size was not increased in pristane-treated Psgl-1(-/-) mice compared to controls, despite evidence of increased nephritis in Psgl-1(-/-) mice. Pristane-treated WT mice showed elevated anti-dsDNA, anti-snRNP, CXCL1, and MCP-1 levels compared to untreated mice; however levels of anti-snRNP, MCP-1, and CXCL1 were reduced in pristane-treated Psgl-1(-/-) mice compared to pristane-treated WT mice. Infiltration of neutrophils and macrophages at the cerebral infarction site were reduced in pristane-treated Psgl-1(-/-) mice compared to pristane-treated WT mice. In conclusion, the increase in stroke size associated with lupus is prevented by Psgl-1 deficiency while nephritis is exacerbated. Therapies targeting Psgl-1 may be useful in the management of SLE patients at high risk of acute vascular complications although elucidation of downstream pathways will be necessary to identify targets that do not promote nephritis. PMID:27357136

  11. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus.

    PubMed

    Liao, Tang-Dong; Nakagawa, Pablo; Janic, Branislava; D'Ambrosio, Martin; Worou, Morel E; Peterson, Edward L; Rhaleb, Nour-Eddine; Yang, Xiao-Ping; Carretero, Oscar A

    2015-05-15

    Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. PMID:25740596

  12. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus

    PubMed Central

    Liao, Tang-Dong; Nakagawa, Pablo; Janic, Branislava; D'Ambrosio, Martin; Worou, Morel E.; Peterson, Edward L.; Rhaleb, Nour-Eddine; Yang, Xiao-Ping

    2015-01-01

    Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. PMID:25740596

  13. Streptococcal Infection-related Nephritis (SIRN) Manifesting Membranoproliferative Glomerulonephritis Type I.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Yamamoto, Yasutaka; Kobayashi, Naoto; Oda, Takashi; Yamaguchi, Yutaka; Shibata, Takanori

    2016-01-01

    We herein report the case of an 18-year-old boy who developed nephrotic syndrome and hypertension after upper airway inflammation. Post-streptococcal acute glomerulonephritis was diagnosed on the basis of a high antistreptolysin O titer, hypocomplementemia, proteinuria, and microscopic hematuria. A renal biopsy was performed due to persistent proteinuria, and the pathological diagnosis was membranoproliferative glomerulonephritis (MPGN) type I. Glomeruli showed positive staining for nephritis-associated plasmin receptor (NAPlr), a nephritogenic group A streptococcal antigen, and plasmin activity was found in a similar distribution as NAPlr deposition. This rare case of streptococcal infection-related nephritis (SIRN) manifesting MPGN type I supports the histological diversity of SIRN. PMID:26984084

  14. Oridonin ameliorates lupus-like symptoms of MRL(lpr/lpr) mice by inhibition of B-cell activating factor (BAFF).

    PubMed

    Zhou, Lin; Sun, Lijuan; Wu, Hongkun; Zhang, Lingzhen; Chen, Mingcang; Liu, Jianwen; Zhong, Renqian

    2013-09-01

    Oridonin, a pharmacologically safe agent extracted from Isodon Serra, has been shown to possess potent anti-inflammatory properties. However, it is not clear whether Oridonin affects B-cell activating factor (BAFF) expression, thereby exerting beneficial effects in the treatment of BAFF-associated autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the current study aimed to find the function of Oridonin in regulation of BAFF and amelioration of SLE. In vitro, we explored the effect of Oridonin on BAFF expression and production in mouse macrophages. Moreover, using a spontaneous murine SLE model, we investigated the role of Oridonin delivery in the treatment of lupus-like disease in MRL(lpr/lpr) mice, by measuring the changes in lupus symptoms, renal damage, BAFF expression, and B cell subsets. Our results showed that Oridonin significantly inhibited BAFF expression in mouse macrophages by suppressing the transcriptional activation of its promoter. And in vivo administration of Oridonin efficiently ameliorated the serological and clinical manifestations of SLE in MRL(lpr/lpr) mice, as shown by increased survival benefit, reduced proteinuria levels, diminished production of specific auto-antibodies, and attenuated renal damage, in association with down-regulation of BAFF and a lower rate of B-cell maturation and differentiation. Thus, it suggests that Oridonin will serve as a novel natural therapeutic strategy for SLE by inhibition of BAFF. PMID:23712004

  15. Immune complex disease with a lupus-like pattern of deposition in an antinuclear antibody-negative patient.

    PubMed

    Pirkle, James L; Freedman, Barry I; Fogo, Agnes B

    2013-07-01

    Immune complex-mediated glomerulonephritis can be caused by a multitude of disease processes and may manifest in a variety of histologic patterns. Lupus nephritis is an immune complex disease, the diagnosis of which requires that the affected patient have systemic lupus erythematosus (SLE). In the absence of SLE, the finding of glomerulonephritis with certain patterns of immune complex deposition characteristic of lupus nephritis has been referred to as lupus-like glomerulonephritis. Immunoglobulin G (IgG), IgA, IgM, complement C3, and C1q deposition in glomerular immune deposits is one such pattern. We report a case of immune complex disease in a primarily membranous distribution with mesangial, subendothelial, and tubular basement membrane deposits with IgG, IgA, IgM, C3, and C1q deposition in a patient with proteinuria, photosensitive dermatitis, and a positive lupus anticoagulant test. The patient had 3 of the clinical criteria for SLE, thus failing to meet the diagnosis based on the American College of Rheumatology definition. In this case, a diagnosis of lupus-like glomerulonephritis was made after other causes of membranous glomerulopathy were excluded. This teaching case highlights the broad differential diagnosis of this pattern of injury and reviews similar cases in the literature. PMID:23548558

  16. Circulating microparticles in systemic Lupus Erythematosus.

    PubMed

    Nielsen, Christoffer Tandrup

    2012-11-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease presenting with a wide array of clinical manifestations and an elusive pathogenesis. A characteristic feature in SLE is the occurrence of autoantibodies against chromatin, double-stranded DNA, and RNA-binding ribonucleoproteins. Observations of defective clearance of dying cells in SLE combined with the generation and exposure of nuclear autoantigens during apoptosis have led to the hypothesis that improperly cleared apoptotic debris constitutes a source of autoantigens capable of triggering autoimmune disease. In blood, circulating, heterogeneous subcellular microparticles (MPs) are released from cells and platelets constitutively and upon cellular activation or apoptosis. Such MPs may reflect the state of their parental cells and tissues, and could serve as markers of pathology. Particular in SLE MPs may serve as carriers of autoantigens and constituents of immune complexes (ICs). The purposes of this PhD thesis were to develop and apply qualitative and quantitative methods to characterize circulating MPs with respect to numbers, cellular origins and composition in a large cohort of well-characterized SLE patients compared to healthy and disease controls and to explore associations with clinical, biochemical and serological parameters. The PhD thesis consists of a review and three papers. In the first paper we show that SLE patients have significantly decreased numbers of annexin V binding MPs and MPs from platelets, leukocytes and endothelial cells using flow cytometry. Two morphologically distinguishable populations of annexin V non-binding MPs were increased in the SLE patients. The annexin V non-binding MPs of most likely cellular origin were associated with the presence of lupus nephritis, markers of increased disease activity and levels of endothelial cell-derived MPs. In the second paper we present the development of a proteomic method to characterize the protein composition of purified

  17. Neurological Sequelae of Lupus

    MedlinePlus

    ... Page Synonym(s): Lupus - Neurological Sequelae, Systemic Lupus Erythematosus Table of Contents (click to jump to sections) What ... health problems and have a normal lifespan with periodic doctor visits and treatments with various drugs. What ...

  18. Living Well with Lupus

    MedlinePlus

    ... Awards Investigator Grants, Fellowships and Career Development Awards & Prizes Peer-Reviewed Grant Program LIFELINE Grant Program 2015 ... following a specific diet or nutrition plan for my lupus? How do I explain lupus to others? ...

  19. Target Awareness: Lupus

    MedlinePlus Videos and Cool Tools

    ... 15 Questions - Spotlight on Clinical Trials 15 Questions - Kidney Issues and Lupus 15 Questions – Pulmonary Issues and ... 15 Questions - Strategies for Restful Sleep 15 Questions - Kidney Issues with Lupus 15 Questions - Cardiovascular Issues with ...

  20. Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype

    PubMed Central

    Ceccarelli, Fulvia; Perricone, Carlo; Borgiani, Paola; Ciccacci, Cinzia; Rufini, Sara; Cipriano, Enrica; Alessandri, Cristiano; Spinelli, Francesca Romana; Sili Scavalli, Antonio; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio

    2015-01-01

    Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association. PMID:26798662

  1. 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

  2. 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.

  3. Elevated sacroilac joint uptake ratios in systemic lupus erythematosus

    SciTech Connect

    De Smet, A.A.; Mahmood, T.; Robinson, R.G.; Lindsley, H.B.

    1984-08-01

    Sacroiliac joint radiographs and radionuclide sacroiliac joint uptake ratios were obtained on 14 patients with active systemic lupus erythematosus. Elevated joint ratios were found unilaterally in two patients and bilaterally in seven patients when their lupus was active. In patients whose disease became quiescent, the uptake ratios returned to normal. Two patients had persistently elevated ratios with continued clinical and laboratory evidence of active lupus. Mild sacroiliac joint sclerosis and erosions were detected on pelvic radiographs in these same two patients. Elevated quantitative sacroiliac joint uptake ratios may occur as a manifestation of active systemic lupus erythematosus.

  4. Immune complexes activate human endothelium involving the cell-signaling HMGB1-RAGE axis in the pathogenesis of lupus vasculitis.

    PubMed

    Sun, Wenping; Jiao, Yulian; Cui, Bin; Gao, Xuejun; Xia, Yu; Zhao, Yueran

    2013-06-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of immune complexes (ICs), which contain a complex mixture of autoantigens nucleic acids, nucleic acids-associated proteins and corresponding autoantibodies. In SLE, ICs are deposited in multiple organs. Vasculopathy and vasculitis in SLE are typical complications and are associated with deposition of ICs on endothelium, endothelial activation and inflammatory cell infiltration. However, the effects of ICs on endothelial cells and the mechanisms involved remain unclear. In this study, we have demonstrated for the first time that ICs upregulated cell surface expression of the receptor for advanced glycation end products (RAGE), the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), increased the secretion of the chemokines interleukin 8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), the proinflammatoy cytokines interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and promoted the activation of the transcription factor NF-κB p65 in human endothelial cells (P<0.05). ICs also increased transendothelial migration of monocytes (P<0.05). One of the mechanisms underlying these activating effects of ICs on human endothelial cells involves cell signaling by high-mobility group box 1 protein (HMGB1)-RAGE axis, as these effects can be partially blocked by HMGB1 A-box, soluble RAGE (sRAGE), SB203580, PD98059, Bay 117082 (P<0.05) and co-treatment with these agents (P<0.05). In conclusion, ICs elicit proinflammatory responses in human endothelial cells and alter their function involving cellular signaling via the HMGB1-RAGE axis in the pathogenesis of SLE vasculitis. PMID:23628898

  5. 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

  6. Chronic active thrombotic microangiopathy in native and transplanted kidneys.

    PubMed

    Zhang, Ping L; Prichard, Jeffery W; Lin, Fan; Shultz, Michael F; Malek, Sayeed K; Shaw, John H; Hartle, James E

    2006-01-01

    We report 2 complicated cases of thrombotic microangiopathy with chronic features and active components. The first case was a 36-yr-old woman with positive anti-DNA antibody and possible lupus cerebritis, who developed thrombotic microangiopathy secondary to a series of syndromes, including preeclampsia and anti-phospholipid antibody syndrome. Renal biopsy revealed no evidence of lupus nephritis and her renal function returned to normal 1 week after the biopsy. The second case was a 46-yr-old man who developed thrombotic microangiopathy of unknown etiology, which led to end-stage renal disease within 6 mo. The patient received a living related-donor transplant, but thrombotic microangiopathy recurred in the donor kidney only 40 days after the renal transplantation. PMID:16951274

  7. TLR7-dependent and FcγR-independent production of type I interferon in experimental mouse lupus

    PubMed Central

    Lee, Pui Y.; Kumagai, Yutaro; Li, Yi; Takeuchi, Osamu; Yoshida, Hideo; Weinstein, Jason; Kellner, Erinn S.; Nacionales, Dina; Barker, Tolga; Kelly-Scumpia, Kindra; van Rooijen, Nico; Kumar, Himanshu; Kawai, Taro; Satoh, Minoru; Akira, Shizuo; Reeves, Westley H.

    2008-01-01

    Increased type I interferon (IFN-I) production and IFN-stimulated gene (ISG) expression are linked to the pathogenesis of systemic lupus erythematosus (SLE). Although the mechanisms responsible for dysregulated IFN-I production in SLE remain unclear, autoantibody-mediated uptake of endogenous nucleic acids is thought to play a role. 2,6,10,14-tetramethylpentadecane (TMPD; also known as pristane) induces a lupus-like disease in mice characterized by immune complex nephritis with autoantibodies to DNA and ribonucleoproteins. We recently reported that TMPD also causes increased ISG expression and that the development of the lupus is completely dependent on IFN-I signaling (Nacionales, D.C., K.M. Kelly-Scumpia, P.Y. Lee, J.S. Weinstein, R. Lyons, E. Sobel, M. Satoh, and W.H. Reeves. 2007. Arthritis Rheum. 56:3770–3783). We show that TMPD elicits IFN-I production, monocyte recruitment, and autoantibody production exclusively through a Toll-like receptor (TLR) 7– and myeloid differentiation factor 88 (MyD88)–dependent pathway. In vitro studies revealed that TMPD augments the effect of TLR7 ligands but does not directly activate TLR7 itself. The effects of TMPD were amplified by the Y-linked autoimmune acceleration cluster, which carries a duplication of the TLR7 gene. In contrast, deficiency of Fcγ receptors (FcγRs) did not affect the production of IFN-I. Collectively, the data demonstrate that TMPD-stimulated IFN-I production requires TLR7/MyD88 signaling and is independent of autoantibody-mediated uptake of ribonucleoproteins by FcγRs. PMID:19047436

  8. The stellar population of the Lupus clouds

    NASA Technical Reports Server (NTRS)

    Hughes, Joanne; Hartigan, Patrick; Krautter, Joachim; Kelemen, Janos

    1994-01-01

    We present photometric and spectroscopic observations of the H alpha emission stars in the Lupus dark cloud complex. We estimate the effective temperatures of the stars from their spectral types and calculate the reddening towards each object from the (R-I) colors. From these data, we derive mass and age distributions for the Lupus stars using a new set of pre-main sequence evolutionar tracks. We compare the results for the Lupus stars with those for a similar population of young stellar objects in Taurus-Auriga and Chamaeleon and with the initial mass function for field stars in the solar neighborhood. From the H-R diagrams, Lupus appears to contain older stars than Taurus. The Lupus dark clouds form a greater proportion of low mass stars than the Taurus complex. Also, the proportion of low mass stars in Lupus is higher than that predicted by the Miller-Scalo initial mass function, and the lowest mass stars in Lupus are less active than similar T Tauri stars in other regions.

  9. Current and emerging treatment options in the management of lupus.

    PubMed

    Jordan, Natasha; D'Cruz, David

    2016-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

  10. Current and emerging treatment options in the management of lupus

    PubMed Central

    Jordan, Natasha; D’Cruz, David

    2016-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

  11. 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

  12. 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

  13. 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

  14. Cutaneous manifestations of lupus erythematosus.

    PubMed

    Laman, S D; Provost, T T

    1994-02-01

    Lupus erythematosus is an autoimmune disease that demonstrates cutaneous, systemic, or both cutaneous and systemic manifestations. This article reviews the cutaneous manifestations of lupus erythematosus. PMID:8153399

  15. Development of tertiary lymphoid structures in the kidneys of pigs with chronic leptospiral nephritis.

    PubMed

    Pezzolato, M; Maina, E; Lonardi, S; Bozzetta, E; Grassi, F; Scanziani, E; Radaelli, E

    2012-01-15

    Tertiary lymphoid organs (TLOs) are structures that are morphologically and functionally similar to secondary lymphoid organs. TLOs usually arise in a background of chronic inflammation. Several histological patterns of interstitial nephritis have been documented in porcine leptospirosis. Among them the lympho-follicular pattern is characterized by infiltrates of mononuclear cells organized in lymphoid follicle-like structures. Immunohistological analysis of 5 cases of porcine lympho-follicular nephritis associated with Leptospira Pomona infection demonstrated the presence of inflammatory cell populations, including B cells, T cells, macrophages and follicular dendritic cells (FDCs), which were compartmentalized as in TLOs. Immunohistochemistry for Leptospira Pomona revealed an intimate association between leptospiral antigen and FDCs. Overexpression of MHCII in different populations of both professional and non-professional antigen presenting cells was also demonstrated. FDCs play role during TLOs induction for their ability to retain non-self antigens in the form of immune complexes, thus causing persistent T cell activation, generation of a complex cytokine network and stimulation of humoral immunity. Sustained bacterial antigen presentation in the context of chronic leptospiral nephritis, may also lead to autoimmune mechanisms involved in the generation of TLOs. Whether lymphoid neogenesis and TLOs play a protective role in porcine leptospiral nephritis is still unclear. PMID:22227076

  16. 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

  17. Radiation nephritis. Clinical manifestations and pathophysiologic mechanisms

    SciTech Connect

    Krochak, R.J.; Baker, D.G.

    1986-05-01

    Radiation nephritis is both volume and dose related. Clinical experience would indicate that a minimum of one third of the renal volume needs to be excluded from nephrotoxic doses which appears to have a threshold of 2,000 cGy. The site of damage leading to renal failure appears to be the microvasculature ultimately expressed as glomerulosclerosis. How much direct damage to the tubular system contributes to this process is unclear, but undoubtedly the resultant systemic physiologic effects potentiate the expression of damage in the irradiated kidney. The acute syndrome, with all the potential manifestations of renal failure, rarely presents sooner than six months and appears to have no clear prodrome, although it would seem reasonable that a subclinical syndrome consisting of abnormalities detectable by urinalysis may occur. Treatment of radiation-induced nephritis or hypertension is no different from treatment for nephritis from any other cause and should be aggressive with lifelong follow-up. Carcinogenesis is a rare late expression of radiation-induced kidney damage. 25 references.

  18. 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

  19. FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in lupus-prone BXSB mice

    SciTech Connect

    Ando, Seiichiro; Amano, Hirofumi; Amano, Eri; Minowa, Kentaro; Watanabe, Takashi; Nakano, Soichiro; Nakiri, Yutaka; Morimoto, Shinji; Tokano, Yoshiaki; Lin, Qingshun; Hou, Rong; Ohtsuji, Mareki; Tsurui, Hiromichi; Hirose, Sachiko; Takasaki, Yoshinari

    2010-04-09

    FTY720 is a novel investigational agent targeting the sphingosine 1-phosphate (S1P) receptors with an ability to cause immunosuppression by inducing lymphocyte sequestration in lymphoid organs. Systemic lupus erythematosus (SLE) is refractory autoimmune disease characterized by the production of a wide variety of autoantibodies and immune complex (IC)-mediated lupus nephritis. Among several SLE-prone strains of mice, BXSB is unique in terms of the disease-associated monocytosis in periphery and the reduced frequency of marginal zone B (MZ B) cells in spleen. In the present study, we examined the effect of FTY720 on lupus nephritis of BXSB mice. FTY720 treatment resulted in a marked decrease in lymphocytes, but not monocytes, in peripheral blood, and caused relocalization of marginal zone B (MZ B) cells into the follicle in the spleen. These changes did not affect the production of autoantibodies, thus IgG and C3 were deposited in glomeruli in FTY720-treated mice. Despite these IC depositions, FTY720-treated mice showed survival advantage with the improved proteinuria. Histological analysis revealed that FTY720 suppressed mesangial cell proliferation and inflammatory cell infiltration. These results suggest that FTY720 ameliorates lupus nephritis by inhibiting the end-stage inflammatory process following IC deposition in glomeruli.

  20. Drug-induced lupus erythematosus

    MedlinePlus

    Complications may include: Infection Thrombocytopenia purpura -- bleeding near the skin surface, resulting from a low number of platelets in the blood Hemolytic anemia Myocarditis Pericarditis Nephritis

  1. Pharmacological Management of Childhood-Onset Systemic Lupus Erythematosus.

    PubMed

    Thorbinson, Colin; Oni, Louise; Smith, Eve; Midgley, Angela; Beresford, Michael W

    2016-06-01

    Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50 years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing B cell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents. PMID:26971103

  2. Severe Nephrotoxic Nephritis following Conditional and Kidney-Specific Knockdown of Stanniocalcin-1

    PubMed Central

    Huang, Luping; Lou, Yahuan; Ju, Huiming; Zhang, Lin; Pan, Jenny Szu-Chin; Ross, April; Sun, Yuxiang; Truong, Luan D.; Sheikh-Hamad, David

    2015-01-01

    Background Inflammation is the hallmark of nephrotoxic nephritis. Stanniocalcin-1 (STC1), a pro-survival factor, inhibits macrophages, stabilizes endothelial barrier function, and diminishes trans-endothelial migration of leukocytes; consistently, transgenic (Tg) overexpression of STC1 protects from nephrotoxic nephritis. Herein, we sought to determine the phenotype of nephrotoxic nephritis after conditional and kidney-specific knockdown of STC1. Methods We used Tg mice that, express either STC1 shRNA (70% knockdown of STC1 within 4d) or scrambled shRNA (control) upon delivery of Cre-expressing plasmid to the kidney using ultrasound microbubble technique. Sheep anti-mouse GBM antibody was administered 4d after shRNA activation; and mice were euthanized 10 days later for analysis. Results Serum creatinine, proteinuria, albuminuria and urine output were similar 10 days after anti-GBM delivery in both groups; however, anti-GBM antibody delivery to mice with kidney-specific knockdown of STC1 produced severe nephrotoxic nephritis, characterized by severe tubular necrosis, glomerular hyalinosis/necrosis and massive cast formation, while control mice manifested mild tubular injury and crescentic glomerulonephritis. Surprisingly, the expression of cytokines/chemokines and infiltration with T-cells and macrophages were also diminished in STC1 knockdown kidneys. Staining for sheep anti-mouse GBM antibody, deposition of mouse C3 and IgG in the kidney, and antibody response to sheep IgG were equal. Conclusions nephrotoxic nephritis after kidney-specific knockdown of STC1 is characterized by severe tubular and glomerular necrosis, possibly due to loss of STC1-mediated pro-survival factors, and we attribute the paucity of inflammation to diminished release of cytokines/chemokines/growth factors from the necrotic epithelium. PMID:26393521

  3. 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

  4. Failure of Gallium-67 scintigraphy to identify reliably noninfectious interstitial nephritis: concise communication

    SciTech Connect

    Graham, G.D.; Lundy, M.M.; Moreno, A.J.

    1983-07-01

    Gallium-67 scintigraphy has been reported to be useful in the diagnosis of noninfectious interstitial nephritis. We studied 12 patients with Ga-67 citrate that were diagnosed as having noninfectious interstitial nephritis on renal biopsy. Only seven of the twelve patients with interstitial nephritis on biopsy were scan-positive. Gallium-67 scintigraphy may not reliably identify noninfectious interstitial nephritis.

  5. Definition of risk factors for death, end stage renal disease, and thromboembolic events in a monocentric cohort of 338 patients with systemic lupus erythematosus

    PubMed Central

    Manger, K; Manger, B; Repp, R; Geisselbrecht, M; Geiger, A; Pfahlberg, A; Harrer, T; Kalden, J

    2002-01-01

    Background: The survival rate in patients with systemic lupus erythematosus (SLE) has improved dramatically during the past four decades to 96.6% (five year) in the Erlangen cohort, but it is nearly three times as high as in an age and sex matched control population. Reasons for death are mainly cardiovascular diseases (37%) and infections (29%). Objective: To find risk factors existing at disease onset for a severe outcome in the Erlangen cohort. Patients and methods: By using a database of 338 patients with SLE from a single centre, documented at least one to 15 years and including Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage score data and index (SDI) and an activity score (European Consensus Lupus Activity Measurement (ECLAM)), a retrospective search was made for risk factors for a severe outcome like death, end stage renal disease (ESRD), and thromboembolic events (TE) in SLE. For this purpose, multivariable Cox regression models were analysed using the statistical package SPSS 10.0 for Windows. Results: The following were defined as risk factors for death at disease onset: male sex (p<0.001, relative risk (RR)=3.5), age >40 at disease onset (p<0.0001, RR=19.9), nephritis (p<0.05, RR=1.6), a reduction of creatinine clearance (p<0.001, RR=1.8), heart disease (p=0.05, RR=1.5), and central nervous system (CNS) disease (p=0.06, RR=1.6). An increase in the SDI of two or more points from the first to the third year of disease was the worst prognostic factor (p<0.0001, RR=7.7). The existence of Ro or nRNP antibodies, or both, was protective (p<0.05, RR =0.1). A low C3 (p<0.01 RR=3.0) and splenomegaly (p<0.01 RR=2.7) at disease onset turned out to be risk factors for ESRD besides a nephritis. In patients with hypertension (p<0.05) and/or high titres of dsDNA antibodies (>70 U/l) (p<0.01) and/or a mean ECLAM score of 4 (p<0.01) in the course of disease, a prevalence of ESRD was recorded in 9% (p<0.05) and 10% (p

  6. Fatigue in systemic lupus erythematosus.

    PubMed

    Ahn, Grace E; Ramsey-Goldman, Rosalind

    2012-04-01

    Systemic lupus erythematosus is a chronic inflammatory autoimmune disease often characterized by fatigue, with significant effects on physical functioning and wellbeing. The definition, prevalence and factors associated with fatigue, including physical activity, obesity, sleep, depression, anxiety, mood, cognitive dysfunction, vitamin D deficiency/insufficiency, pain, effects of medications and comorbidities, as well as potential therapeutic options of fatigue in the systemic lupus erythematosus population are reviewed. Due to variability in the reliability and validity of various fatigue measures used in clinical studies, clinical trial data have been challenging to interpret. Further investigation into the relationships between these risk factors and fatigue, and improved measures of fatigue, may lead to an improvement in the management of this chronic inflammatory disease. PMID:22737181

  7. IL-17 promotes murine lupus.

    PubMed

    Amarilyo, Gil; Lourenço, Elaine V; Shi, Fu-Dong; La Cava, Antonio

    2014-07-15

    The proinflammatory activity of IL-17-producing Th17 cells has been associated with the pathogenesis of several autoimmune diseases. In this article, we provide direct evidence for a role of IL-17 in the pathogenesis of systemic lupus erythematosus (SLE). The induction of SLE by pristane in IL-17-sufficient wild-type mice did not occur in IL-17-deficient mice, which were protected from development of lupus autoantibodies and glomerulonephritis. The protection from SLE in IL-17-deficient mice was associated with a reduced frequency of CD3(+)CD4(-)CD8(-) double-negative T cells and an expansion of CD4(+) regulatory T cells, and did not depend on Stat-1 signaling. These data affirm the key role of IL-17 in the pathogenesis of SLE and strengthen the support for IL-17 blockade in the therapy of SLE. PMID:24920843

  8. Haematological manifestations of lupus

    PubMed Central

    Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

    2015-01-01

    Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

  9. [Alveolar hemorrhage secondary to generalized systemic lupus erithematosus treated with recombinant activated factor VII. Case report and literature review].

    PubMed

    Carrillo-Esper, Raúl; Elizondo-Argueta, Sandra; Sánchez-Zúñiga, Martín de Jesús; Carrillo-Córdova, Jorge Raúl

    2007-01-01

    Alveolar hemorrhage is a severe complication of systemic lupus erithematosus (SLe) associated with high mortality. Treatment includes administration of steroids and cyclophosphamide. Additionally, some reports have recommended the use of plasmapheresis, azathioprine and methotrexate. There is a single case reported in the literature in which recombinant activatedfactor VII (rFVIIa) was used to control severe hemorrhage secondary to alveolitis unresponsive to standard treatment. We report the case of a patient with SLE who developed severe alveolar hemorrhage unresponsive to standard measures, but who was successfully treated with rFVIIa. PMID:17388100

  10. Clinical Features of Systemic Lupus Erythematosus Patients Complicated With Evans Syndrome

    PubMed Central

    Zhang, Lili; Wu, Xiuhua; Wang, Laifang; Li, Jing; Chen, Hua; Zhao, Yan; Zheng, Wenjie

    2016-01-01

    Abstract The aim of the study was to investigate the clinical features of systemic lupus erythematous (SLE) complicated with Evans syndrome (ES). We conducted a retrospective case–control study to compare the clinical and laboratory features of age- and gender-matched lupus patients with and without ES in 1:3 ratios. In 5724 hospitalized SLE patients, we identified 27 (0.47%, 22 women and 5 men, average age 34.2 years) SLE patients complicated with ES. Fifteen patients (55.6%) presented with hematologic abnormalities initially, including 6 (22.2%) cases of isolated ITP, 4 (14.8%) cases of isolated AIHA, and 5 (18.5%) cases of classical ES. The median intervals between hematological presentations the diagnosis of SLE was 36 months (range 0–252). ES developed after the SLE diagnosis in 4 patients (14.8%), and concomitantly with SLE diagnosis in 8 patients (29.6%). Systemic involvements are frequently observed in SLE patients with ES, including fever (55.6%), serositis (51.9%), hair loss (40.7%), lupus nephritis (37%), Raynaud phenomenon (33.3%), neuropsychiatric (33.3%) and pulmonary involvement (25.9%), and photosensitivity (25.9%). The incidence of photosensitivity, hypocomplementemia, elevated serum IgG level, and lupus nephritis in patients with ES or without ES was 25.9% vs 6.2% (P = 0.007), 88.9% vs 67.1% (P = 0.029), 48.1% vs 24.4% (P = 0.021), and 37% vs 64.2% (P = 0.013), respectively. Twenty-five (92.6%) patients achieved improvement following treatment of glucocorticoids and immunosuppressants as well as splenectomy, whereas 6 patients experienced the relapse and 1 patient died from renal failure during the follow-up. ES is a relatively rare complication of SLE. Photosensitivity, hypocomplementemia, and elevated serum IgG level were frequently observed in ES patients, but lupus nephritis was less observed. More than half of patients presented with hematological manifestation at onset, and progress to typical lupus over months to years

  11. Psgl-1 Deficiency is Protective against Stroke in a Murine Model of Lupus

    PubMed Central

    Wang, Hui; Knight, Jason S.; Hodgin, Jeffrey B.; Wang, Jintao; Guo, Chiao; Kleiman, Kyle; Eitzman, Daniel T.

    2016-01-01

    Systemic lupus erythematosus (SLE) is associated with an elevated risk of vascular complications, including premature stroke. Therapies targeting leukocyte recruitment may be beneficial in reducing vascular complications associated with SLE. Lupus was induced in female wild-type (WT) and P-selectin glycoprotein ligand-1 deficient (Psgl-1−/−) mice with pristane. Stroke was induced following photochemical injury to the middle cerebral artery (MCA). Stroke size was increased in pristane-treated WT mice compared to non-pristane-treated WT controls. However, stroke size was not increased in pristane-treated Psgl-1−/− mice compared to controls, despite evidence of increased nephritis in Psgl-1−/− mice. Pristane-treated WT mice showed elevated anti-dsDNA, anti-snRNP, CXCL1, and MCP-1 levels compared to untreated mice; however levels of anti-snRNP, MCP-1, and CXCL1 were reduced in pristane-treated Psgl-1−/− mice compared to pristane-treated WT mice. Infiltration of neutrophils and macrophages at the cerebral infarction site were reduced in pristane-treated Psgl-1−/− mice compared to pristane-treated WT mice. In conclusion, the increase in stroke size associated with lupus is prevented by Psgl-1 deficiency while nephritis is exacerbated. Therapies targeting Psgl-1 may be useful in the management of SLE patients at high risk of acute vascular complications although elucidation of downstream pathways will be necessary to identify targets that do not promote nephritis. PMID:27357136

  12. Fatal suppurative nephritis caused by Pseudomonas in a chimpanzee

    USGS Publications Warehouse

    Migaki, G.; Asher, D.M.; Casey, H.W.; Locke, L.N.; Gibbs, C.J.; Gajdusek, C.

    1979-01-01

    Reports of nephritis in chimpanzees are relatively rare, compared with those in other nonhuman primates. McClure and Guilloud reported chronic pyelonephritis in a 35-year-old female chimpanzee; Schmidt and Butler reported glomerulonephritis in an 11-year-old female chimpanzee, and Kim reported on a 12-year-old male with subacute interstitial nephritis in a chimpanzee after the animal had recurrent hemolysis due to phenolic intoxication. The present report deals with supprative nephritis caused by Pseudomonas resulting in renal failure in a chimpanzee.

  13. 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

  14. Lupus and Your Body

    MedlinePlus

    ... Recipients 2014 LIFELINE Grant Program™ Recipients Lupus Insight Prize Evelyn V. Hess, MD, MACP, MACR, Award About ... V. Hess Mary Betty Stevens, MD, Young Investigator Prize About Dr. Mary Betty Stevens Career Development Award ...

  15. Lupus Foundation of America

    MedlinePlus

    ... Lupus Q&A with Sheri R. Abrams - Social Security and Disability Q&A with Dr. Betsy Blazek- ... Life Insurance Employment, Disability and Legal Issues Social Security Disability Applying for Social Security Disability Work Related ...

  16. Systemic lupus erythematosus.

    PubMed

    Samuelson, S J; Friedlander, A H; Swerdloff, M

    1980-04-01

    A case of osteomyelitis of the mandible in a patient with systemic lupus erythematosus is described. Both the disease process and the treatment modalities must be understood for correct management. PMID:6928895

  17. Clinical and pathologic considerations of the qualitative and quantitative aspects of lupus nephritogenic autoantibodies: A comprehensive review.

    PubMed

    Gatto, Mariele; Iaccarino, Luca; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

    2016-05-01

    Autoantibodies are key mediators in determining the clinical manifestations of systemic lupus erythematosus (SLE). The mechanisms by which antibodies may be harmful to self tissues encompass complement mediated inflammation, cell apoptosis and immune-complexes mediated damage, however the precise cooperation of antibodies in SLE have not been unravelled so far. Lupus nephritis (LN) is a protean feature of SLE resulting in wide variety of symptoms including asymptomatic proteinuria, mild renal disease until end-stage renal failure which are triggered by complex autoantibody interactions. Novel clues concerning development and self-maintenance of LN have come to light in recent times, pointing straight to a multistep inflammatory process which is incited by anti-chromatin antibodies, the best known being anti-DNA and anti-nucleosome antibodies, culminating in a self-maintaining inflammatory loop with spreading of glomerular inflammation. In the maintenance of the inflammatory process pro-inflammatory antibodies are involved, among which anti-C1q are thought to play a major role, whereas hindrance of the nephritic process could be actively mediated by protective autoantibodies. Despite being so relevant in occurrence of LN, nor anti-chromatin neither anti-C1q antibodies have been precisely characterized in terms of origin, antigen specificity and mechanisms of action. Moreover, novel autoantibodies are emerging in LN which can modify disease course, whereas the pathogenic value of a myriad of cross-reactive antibodies has been progressively challenged. The aim of this review is to give a comprehensive view of known and emerging autoantibody reactivities involved in renal inflammation and damage going over their origin, mechanisms of action and interactions in determining LN course. PMID:26879422

  18. Belimumab in systemic lupus erythematosus

    PubMed Central

    Vilas-Boas, Andreia; Morais, Sandra A; Isenberg, David A

    2015-01-01

    Systemic lupus erythematosus (SLE) is one of the most challenging autoimmune disorders with a complex pathophysiology and diverse clinical presentation. Many drugs have been used to treat SLE with suboptimal results, especially in patients with moderate-to-severe disease. Belimumab is the first biological drug to be approved for the treatment of SLE in more than 50 years. This monoclonal antibody blocks B-cell activating factor, a cytokine important for B-cell differentiation and survival. In this review we focus on the activity of belimumab in patients with SLE and discuss the controversies of its use. PMID:26509047

  19. Unmet medical needs in systemic lupus erythematosus

    PubMed Central

    2012-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease of diverse manifestations, with onset usually in young women in the third to fourth decade of life. The chronic nature of this relapsing remitting disease leads to organ damage accrual over time. Mortality and morbidity are increased in patients with SLE compared with the general population. Therapeutic advances over the last few decades have led to significant improvements in patient outcomes. Five-year survival has improved to over 90% from a low of 50% in the 1950s. However, multiple aspects of the management of SLE patients are still far from optimal. Early diagnosis remains a challenge; diagnostic delays leading to delay in definitive treatment are common. Monitoring treatment remains problematic due to the paucity of sensitive biomarkers. Current treatment regimens rely heavily on corticosteroids, even though corticosteroids are well known to cause organ damage. Treatment of refractory disease manifestations such as nephritis, recalcitrant cutaneous lesions and neurological involvement require new approaches with greater efficacy. Cognitive dysfunction is common in SLE patients, but early recognition and adequate treatment are yet to be established. Premature accelerated atherosclerosis remains a leading cause of morbidity and mortality. Fatigue is one of the most disabling symptoms, and contributes to the poor quality of life in patients with SLE. Ongoing research in SLE faces many challenges, including enrollment of homogeneous patient populations, use of reliable outcome measures and a standard control arm. The current review will highlight some of the outstanding unmet challenges in the management of this complex disease. PMID:23281889

  20. Lupus anticoagulants and antiphospholipid antibodies

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  1. Lupus Therapies Continue to Evolve

    MedlinePlus

    ... common form, called systemic lupus erythematosus, commonly causes mouth sores, rash, fatigue, joint pain and swelling, as well ... symptoms such as fatigue, rashes, joint pain or mouth sores. Part of what makes lupus research such a ...

  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. 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

  4. Clinical outcome measures for Cutaneous Lupus Erythematosus

    PubMed Central

    Albrecht, Joerg; Werth, Victoria P.

    2011-01-01

    Cutaneous lupus erythematosus is a clinically heterogeneous group of rare skin diseases that only rarely have been subjected to controlled clinical trials. This may be have been partly due to a lack of suitable validated outcome instruments. Recently the FDA mandated that organ specific trials for lupus erythematosus need to use a combination of different outcome measures. The patient’s condition needs to be assessed in terms of quality of life, the patient’s global response and organ specific instruments that measure activity of the disease as well as damage due to the disease. For the skin the only formally validated and published instrument is currently the Cutaneous Lupus Erythematosis Disease Area and Severity Index (CLASI). This paper discusses the background of the development of the CLASI as well as issues related to its use and interpretation in the context of clinical research of CLE. PMID:20693208

  5. Acute Interstitial Nephritis Following Multiple Asian Giant Hornet Stings

    PubMed Central

    Li, Xiang-Dong; Liu, Zheng; Zhai, Ying; Zhao, Ming; Shen, Hai-Yan; Li, Yi; Zhang, Bo; Liu, Tao

    2015-01-01

    Patient: Male, 42 Final Diagnosis: Acute interstitial nephritis Symptoms: Difficulty breathing • headache • numbness • oliguria Medication: Methylprednisolone Clinical Procedure: Plasma exchange Specialty: Nephrology Objective: Rare disease Background: The Asian giant hornet is the largest wasp species in the world. Its stings can cause acute interstitial nephritis and acute renal failure. From July to October, 2013, Asian giant hornet attacks have killed 42 people and injured 1675 people with their powerful venomous stings in Hanzhong, Ankang, and Shangluo, three cities in the southern part of Shaanxi Province, China. Case Report: We report here a case of a 42-year-old man with acute interstitial nephritis following multiple Asian giant hornet stings. On admission, the patient had difficulty breathing, headache, and numbness in both limbs (arm and leg). He was treated in the Emergency Department and Department of Nephrology with plasma exchange and dialysis within 24 hours after being stung. A kidney biopsy revealed acute interstitial nephritis with interstitial infiltrations of eosinophils and lymphocytes. After intensive treatment, his liver function recovered within 10 days. Along with oral methylprednisolone, his renal function recovered 1 month later. Conclusions: This case shows that acute interstitial nephritis happens several days after being stung. Since the number of deaths in southern Shaanxi province is much higher than other places, our report draws the attention of fellow clinicians to the acute interstitial nephritis following multiple Asian giant hornet stings. PMID:26076055

  6. 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

  7. Posterior reversible encephalopathy syndrome: an acute manifestation of systemic lupus erythematous.

    PubMed

    Chan, Dexter Yak Seng; Ong, Yin Sheng

    2013-09-01

    Stroke mimickers are common, and they represent a diagnostic dilemma for clinicians. Many, like posterior reversible encephalopathy syndrome (PRES), are easily reversible. The manifestation of PRES is characterised by headaches, convulsions, altered mental functioning and blindness. In most cases, computed tomography of the brain will show hypodense lesions in the parieto-occpitial lobe, which only further confounds the physician. Although this syndrome is uncommon, prompt and accurate recognition allows early treatment, which has been shown to produce favourable outcomes. Herein, we report the case of a 54-year-old woman, who presented with PRES, as an acute manifestation of systemic lupus erythematous (SLE) and lupus nephritis. The patient was initially thought to be experiencing an ischaemic stroke, but the diagnosis was later changed. On management of her underlying condition, her symptoms resolved. PRES should be recognised as an acute emergency manifestation of SLE. It should not be mistaken for an ischaemic stroke as inappropriate treatment could have adverse outcomes. PMID:24068069

  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. Assessment of the translational value of mouse lupus models using clinically relevant biomarkers.

    PubMed

    Bender, Andrew T; Wu, Yin; Cao, Qiongfang; Ding, Yueyun; Oestreicher, Judith; Genest, Melinda; Akare, Sandeep; Ishizaka, Sally T; Mackey, Matthew F

    2014-06-01

    Lupus is an autoimmune disease with a poorly understood etiology that manifests with a diverse pathology. This heterogeneity has been a challenge to clinical drug development efforts. A related difficulty is the uncertain translational power of animal models used for evaluating potential drug targets and candidate therapeutics, because it is unlikely that any 1 preclinical model will recapitulate the spectrum of human disease. Therefore, multiple models, along with an understanding of the immune mechanisms that drive them, are necessary if we are to use them to identify valid drug targets and evaluate candidate therapies successfully. To this end, we have characterized several different mouse lupus models and report their differences with respect to biomarkers and symptoms that are representative of the human disease. We compared the pristane-induced mouse lupus disease model using 3 different strains (DBA/1, SJL, BALB/c), and the spontaneous NZB x NZW F1(NZB/W) mouse model. We show that the models differ significantly in their autoantibody profiles, disease manifestations such as nephritis and arthritis, and expression of type I interferon-regulated genes. Similar to the NZB/W model, pristane-induced disease in SJL mice manifests with nephritis and proteinuria, whereas the pristane-treated DBA/1 mice develop arthritis and an interferon-driven gene signature that closely resembles that in human patients. The elucidation of each model's strengths and the identification of translatable biomarkers yields insight for basic lupus research and drug development, and should assist in the proper selection of models for evaluating candidate targets and therapeutic strategies. PMID:24462761

  10. Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Induce a Proinflammatory Phenotype in Macrophages.

    PubMed

    Thanei, Sophia; Trendelenburg, Marten

    2016-03-01

    Anti-C1q autoantibodies (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE) and correlate with the occurrence of proliferative lupus nephritis. A previous study of anti-C1q in experimental lupus nephritis demonstrated an important role for FcγRs in the pathogenesis of lupus nephritis, suggesting a direct effect on phagocytes. Therefore, we developed an in vitro model to study the effect of SLE patient-derived anti-C1q bound to immobilized C1q (imC1q) on human monocyte-derived macrophages (HMDMs) obtained from healthy donors and SLE patients. HMDMs were investigated by analyzing the cell morphology, LPS-induced cytokine profile, surface marker expression, and phagocytosis rate of apoptotic Jurkat cells. Morphologically, bound anti-C1q induced cell aggregations of HMDMs compared with imC1q or IgG alone. In addition, anti-C1q reversed the effect of imC1q alone, shifting the LPS-induced cytokine release toward a proinflammatory response. FcγR-blocking experiments revealed that the secretion of proinflammatory cytokines was mediated via FcγRII. The anti-C1q-induced inflammatory cytokine profile was accompanied by a downregulation of CD163 and an upregulation of LPS-induced CD80, CD274, and MHC class II. Finally, HMDMs primed on bound anti-C1q versus imC1q alone displayed a significantly lower phagocytosis rate of early and late apoptotic cells accompanied by a reduced Mer tyrosine kinase expression. Interestingly, anti-C1q-dependent secretion of proinflammatory cytokines was similar in SLE patient-derived cells, with the exception that IL-10 was slightly increased. In conclusion, anti-C1q induced a proinflammatory phenotype in HMDMs reversing the effects of imC1q alone. This effect might exacerbate underlying pathogenic mechanisms in lupus nephritis. PMID:26829984

  11. Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation

    PubMed Central

    Wu, Yanwei; He, Shijun; Bai, Bingxin; Zhang, Luyao; Xue, Lu; Lin, Zemin; Yang, Xiaoqian; Zhu, Fenghua; He, Peilan; Tang, Wei; Zuo, Jianping

    2016-01-01

    We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRL/lpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus (SLE). When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/lpr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies (ANAs) and of the pathogenic cytokines IL-6, IL-10 and IL-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/lpr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell (PC) numbers. Ex vivo, SM934 suppressed the Toll-like receptor (TLR)-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-κB phosphorylation. In human peripheral blood mononuclear cells (PBMCs), consistent with the results in MRL/lpr mice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/lpr mice by suppressing B cell activation and plasma cell formation. PMID:25942599

  12. Epigenetics and Systemic Lupus Erythematosus: Unmet Needs.

    PubMed

    Meroni, Pier Luigi; Penatti, Alessandra Emiliana

    2016-06-01

    Systemic lupus erythematosus (SLE) is a chronic relapsing-remitting autoimmune disease affecting several organs. Although the management of lupus patients has improved in the last years, several aspects still remain challenging. More sensitive and specific biomarkers for an early diagnosis as well as for monitoring disease activity and tissue damage are needed. Genome-wide association and gene mapping studies have supported the genetic background for SLE susceptibility. However, the relatively modest risk association and the studies in twins have suggested a role for environmental and epigenetic factors, as well as genetic-epigenetic interaction. Accordingly, there is evidence that differences in DNA methylation, histone modifications, and miRNA profiling can be found in lupus patients versus normal subjects. Moreover, impaired DNA methylation on the inactive X-chromosome was suggested to explain, at least in part, the female prevalence of the disease. Epigenetic markers may be help in fulfilling the unmet needs for SLE by offering new diagnostic tools, new biomarkers for monitoring disease activity, or to better characterize patients with a silent clinical disease but with an active serology. Anti-DNA, anti-phospholipid, and anti-Ro/SSA autoantibodies are thought to be pathogenic for glomerulonephritis, recurrent thrombosis and miscarriages, and neonatal lupus, respectively. However, tissue damage occurs occasionally or, in some patients, only in spite of the persistent presence of the antibodies. Preliminary studies suggest that epigenetic mechanisms may explain why the damage takes place in some patients only or at a given time. PMID:26206675

  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. 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

  15. Large pericardial effusions due to systemic lupus erythematosus: a report of eight cases.

    PubMed

    Weich, H S v H; Burgess, L J; Reuter, H; Brice, E A; Doubell, A F

    2005-01-01

    The aim of this study was to describe the clinical, echocardiographic and laboratory characteristics of large pericardial effusions and cardiac tamponade secondary to systemic lupus erythematosus (SLE). An ongoing prospective study was conducted at Tygerberg Academic Hospital, South Africa between 1996 and 2002. All patients older than 13 years presenting with large pericardial effusions (> 10 mm) requiring pericardiocentesis were included. Eight cases (out of 258) were diagnosed with SLE. The mean (SD) age was 29.5 (10.7) years. Common clinical features were Raynaud's phenomenon, arthralgia and lupus nephritis class III/IV. Echocardiography showed Libman-Sacks endocarditis (LSE) in all the mitral valves. Two patients developed transient left ventricular dysfunction; both these patients had pancarditis. Typical serological findings included antinuclear antibodies, anti-double stranded DNA antibodies, low complement C4 levels and low C3 levels. CRP was elevated in six cases. Treatment consisted of oral steroids and complete drainage of the pericardial effusions. No repeat pericardial effusions or constrictive pericarditis developed amongst the survivors (3.1 years follow up). This study concludes that large pericardial effusions due to SLE are rare, and associated with nephritis, LSE and myocardial dysfunction. Treatment with steroids and complete drainage is associated with a good cardiac outcome. PMID:16038109

  16. BANK1 Regulates IgG Production in a Lupus Model by Controlling TLR7-Dependent STAT1 Activation

    PubMed Central

    Iida, Ryuji; Bagavant, Harini; Alarcón-Riquelme, Marta E.

    2016-01-01

    The purpose of our study was to investigate the effects of the adaptor Bank1 in TLR7 signaling using the B6.Sle1.yaa mouse, a lupus model that develops disease through exacerbated TLR7 expression. Crosses of B6.Sle1.yaa with Bank1-/- mice maintained several B and myeloid cell phenotypes close to normal wild-type levels. Most striking was the reduction in total serum IgG antibodies, but not of IgM, and reduced serum levels of autoantibodies, IL-6, and BAFF. Bank1 deficiency did modify numbers of MZ B cells and total B cell numbers, as well as expression of CXCR4 by follicular helper T cells. Other T cell changes were not observed. Bank1 deficiency did not modify numbers of germinal center B cells or plasma cells or clinical disease outcomes. Purified B cells from Bank1 deficient mice had strongly reduced Ifnb, Ifna4, Irf7, Aicda and Stat1 gene expression following TLR7 agonist stimulation. Interestingly, phosphorylation of Tyr701, but not of Ser727 of STAT1, was impaired in splenic B cells from B6.Sle1.yaa.Bank1-/- mice, as was the nuclear translocation of IRF7 in response to TLR7 agonist stimulation. Further, Bank1 deficiency in B6.Sle1.yaa mice reduced the production of IgG2c after in vitro TLR7 agonist stimulation. Our results demonstrate that Bank1 controls TLR7-mediated type I interferon production. Combined with the control of the nuclear translocation of IRF7, the modulation of STAT1 transcription and phosphorylation, Bank1 contributes to IgG production during development of autoimmune disease. PMID:27228057

  17. DEFICIENCY OF THE TYPE I INTERFERON RECEPTOR PROTECTS MICE FROM EXPERIMENTAL LUPUS

    PubMed Central

    Nacionales, Dina C.; Kelly-Scumpia, Kindra M.; Lee, Pui Y.; Weinstein, Jason S.; Lyons, Robert; Sobel, Eric; Satoh, Minoru; Reeves, Westley H.

    2010-01-01

    Objective Systemic lupus erythematosus (SLE) is diagnosed by a spectrum of clinical manifestations and autoantibodies associated with abnormal expression of Type I interferon (IFN-I) stimulated genes (ISGs). The role of IFN-I in the pathogenesis of SLE remains uncertain, partly due to the lack of suitable animal models. The objective of this study was to examine the role of IFN-I signaling in the pathogenesis of murine lupus induced by 2, 6, 10, 14 tetramethylpentadecane (TMPD). Methods 129Sv IFN-I receptor deficient (IFNAR−/−) and control 129Sv mice were treated i.p. with TMPD. The expression of ISGs was measured by real-time PCR. Autoantibody production was evaluated by immunofluorescence and ELISA. Proteinuria and renal glomerular cellularity were measured and renal immune complexes were examined by immunofluorescence. Results Increased ISG expression was seen in peripheral blood of TMPD-treated wild type but not IFNAR−/− mice. TMPD did not induce lupus-specific autoantibodies (anti-nRNP/Sm, -dsDNA) in IFNAR−/− mice, whereas 129Sv controls developed these specificities. Although glomerular immune complexes were present in IFNAR−/− mice, proteinuria and glomerular hypercellularity did not develop, unlike TMPD-treated controls. Thus, consistent with the association of increased ISG expression with lupus-specific autoantibodies, and nephritis in humans, these clinical and serological manifestations were strongly dependent on IFNAR signaling in TMPD-treated mice. Conclusion Signaling via the IFNAR is central to the pathogenesis of autoantibodies and glomerulonephritis in TMPD-lupus, consistent with a similar role in human SLE. TMPD-lupus is the first animal model shown to recapitulate the interferon signature in peripheral blood. PMID:17968932

  18. Genetics Home Reference: systemic lupus erythematosus

    MedlinePlus

    ... Genetics Home Health Conditions systemic lupus erythematosus systemic lupus erythematosus Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Systemic lupus erythematosus (SLE) is a chronic disease that causes ...

  19. S.L.E. Lupus Foundation

    MedlinePlus

    ... Strategies for Speaking with Your Lupus Doctor Traveling Smart with Lupus 21st Century Cures A Year’s Worth ... Kickoff 2009 Camp Sunshine 2009 ING New York City Marathon 2009 Life Without Lupus® Gala 2010 Camp ...

  20. Ectopic Axillary Breast during Systemic Lupus

    PubMed Central

    Ben Dhaou, Besma; Boussema, Fatma; Aydi, Zohra; Baili, Lilia; Rokbani, Lilia

    2012-01-01

    Many breast changes may occur in systemic lupus erythematosus. We report a 41-year-old woman with lupus who presented three years after the onset of lupus an ectopic mammary gland confirmed by histological study. PMID:22924044

  1. Suspected acute interstitial nephritis induced by colistin.

    PubMed

    Kallel, Hatem; Hamida, Chokri Ben; Ksibi, Hichem; Bahloul, Mabrouk; Hergafi, Leila; Chaari, Anis; Chelly, Hedi; Bouaziz, Mounir

    2005-01-01

    We describe a 35-year-old male admitted to the intensive care unit (ICU) for acute exacerbation of chronic obstructive pulmonary disease (COPD). He developed ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and was treated with imipenem and colistin without any renal toxicity. The patient was readmitted to the ICU for a 2nd and a 3rd exacerbation of COPD and was again treated with imipenem and colistin. In both episodes, he developed rapid worsening in renal function, which improved following colistin withdrawal. Use of the Naranjo ADR probability scale indicated a probable relationship between the renal failure and the colistin therapy. In addition, the time course of events suggested that colistin was the cause of acute interstitial nephritis in this patient. We conclude that our patient had a possible acute allergic reaction to colistin since the 1st introduction was not associated with any renal toxicity and renal failure was observed on the 1st day of the 2nd and the 3rd initiation of colistin therapy, respectively. PMID:16013023

  2. Acute interstitial nephritis - a reappraisal and update.

    PubMed

    Raghavan, Rajeev; Eknoyan, Garabed

    2014-09-01

    Acute interstitial nephritis (AIN) is an under recognized and under diagnosed cause of acute kidney injury (AKI). It is estimated to account for 15 - 20% of cases of AKI; it is the reported diagnosis in 2.8% of all kidney biopsies, and 13.5% of biopsies done specifically for acute renal failure. Considerable evidence implicates antigen initiated cell-mediated injury in the pathogenesis of AIN. Drugs account for 70% of all cases, with over 150 different agents incriminated. The remaining cases are due to infections, autoimmune diseases, and rarely idiopathic. The central component of renal injury in AIN is altered tubular function, which usually precedes decrements in filtration rate. The key to early diagnosis is vigilance for the presence of tubular dysfunction in non-oliguric individuals, especially in patients with modest but gradual increments in creatinine level. The utility of urinary biomarkers to diagnose AIN in its early nascent and potentially reversible stage remains to be determined. Prompt recognition, elimination of the offending source of antigen, and use of a limited course of steroid therapy where indicated, will result in complete resolution in ~ 65% of cases, partial resolution in up to 20%, and irreversible damage in the rest. PMID:25079860

  3. Immunologic Observations in Canine Interstitial Nephritis

    PubMed Central

    Krohn, Kai; Mero, Matti; Oksanen, Aili; Sandholm, Markus

    1971-01-01

    Immunofluorescence studies in cases of chronic interstitial nephritis (CIN) in the dog demonstrated deposition of canine IgC and C'3 in the thickened capillary walls of the glomeruli and in the mesangium. Eluates obtained from the nephritic kidneys contained antibodies of IgG type and reacted with autologous or homologous nephritic kidneys but not with normal kidneys or with any normal canine tissue. The staining pattern of fluorescein-conjugated eluates was similar to that obtained with anti-canine IgG or anti-canine C'3. The eluates did not contain leptospiral antibodies. The findings indicate that complement-fixing immune complexes are deposited in the damaged glomeruli in CIN. The nature of the antigen involved in these complexes is unknown, but it does not seem to be a component of normal canine tissue and could thus be viral or bacterial. ImagesFig 5Fig 6Fig 7Fig 8Fig 13Fig 14Fig 15Fig 16Fig 9Fig 10Fig 11Fig 12Fig 1Fig 2Fig 3Fig 4 PMID:4106382

  4. VGX-1027 modulates genes involved in lipopolysaccharide-induced Toll-like receptor 4 activation and in a murine model of systemic lupus erythematosus

    PubMed Central

    Fagone, Paolo; Muthumani, Karuppiah; Mangano, Katia; Magro, Gaetano; Meroni, Pier Luigi; Kim, Joseph J; Sardesai, Niranjan Y; Weiner, David B; Nicoletti, Ferdinando

    2014-01-01

    VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid] is a small molecule compound with immunomodulatory properties, which favourably influences the development of immuno-inflammatory and autoimmune diseases in different animal models such as type 1 diabetes mellitus, pleurisy, rheumatoid arthritis and inflammatory bowel disease. However, the precise mechanism of action of VGX-1027 remains to be ascertained. With this aim, we have studied the immunomodulatory effects of VGX-1027 in vitro, using a genome-wide oligonucleotide microarray approach, and in vivo, using the NZB/NZW F1 model of systemic lupus erythematosus. Microarray data revealed that the administration of VGX-1027 profoundly affected the immune response to exogenous antigens, by modulating the expression of genes that are primarily involved in antigen processing and presentation as well as genes that regulate immune activation. When administered in vivo VGX-1027 ameliorated the course of the disease in the NZB/NZW F1 mice, which correlated with higher per cent survival and improved clinical and histopathological signs. The data presented herein support the theory that VGX-1027 modulates immunity, probably by inhibiting inflammatory antigen presentation and so limiting immune cell expansion. PMID:24527796

  5. 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

  6. Challenges for lupus management in emerging countries.

    PubMed

    Tazi Mezalek, Zoubida; Bono, Wafaa

    2014-06-01

    In emerging countries, systemic lupus erythematosus (SLE) has been associated with several unfavorable outcomes including disease activity, damage accrual, work disability and mortality. Poor socioeconomic status (SES) and lack of access to healthcare, especially in medically underserved communities, may be responsible for many of the observed disparities. Diagnostic delay of SLE or for severe organ damages (renal involvement) have a negative impact on those adverse outcomes in lupus patients who either belong to minority groups or live in emerging countries. Longitudinal and observational prospective studies and registries may help to identify the factors that influence poor SLE outcomes in emerging countries. Infection is an important cause of mortality and morbidity in SLE, particularly in low SES patients and tuberculosis appears to be frequent in SLE patients living in endemic areas (mainly emerging countries). Thus, tuberculosis screening should be systematically performed and prophylaxis discussed for patients from these areas. SLE treatment in the developing world is restricted by the availability and cost of some immunosuppressive drugs. Moreover, poor adherence has been associated to bad outcomes in lupus patients with a higher risk of flares, morbidity, hospitalization, and poor renal prognosis. Low education and the lack of money are identified as the main barrier to improve lupus prognosis. Newer therapeutic agents and new protocols had contributed to improve survival in SLE. The use of corticoid-sparing agents (hydroxychloroquine, methotrexate, azathioprine and mycophenolate mofetif) is one of the most useful strategy; availability of inexpensive generics may help to optimize access to these medications. PMID:24857588

  7. 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

  8. Acute interstitial nephritis following kudzu root juice ingestion.

    PubMed

    Jung, Jae Myun; Kwon, Soon Hyo; Noh, Hyunjin; Han, Dong Cheol; Jeon, Jin Seok; Jin, So Young

    2013-10-01

    Recently, the use of herbal remedies and complementary and alternative medicine has increased globally. Kudzu root (Pueraria lobata) is a plant commonly used in traditional medicine to promote health. A middle-aged woman consumed kudzu root juice to promote health and well-being for 10 days. Subsequently, she developed anorexia, epigastric discomfort and azotemia. These symptoms improved rapidly within several days after discontinuation of the suspected offending agent and conservative treatment. Acute interstitial nephritis was diagnosed by renal biopsy. To our knowledge, this is the first case report describing acute interstitial nephritis following the ingestion of kudzu root juice. PMID:24060140

  9. Inhibition of C5a receptor alleviates experimental CNS lupus

    PubMed Central

    Jacob, Alexander; Hack, Bradley; Bai, Tao; Brorson, James R.; Quigg, Richard J.; Alexander, Jessy J.

    2010-01-01

    To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF-α and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK, pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/lpr brains. MRL/lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus. PMID:20207017

  10. Dissection of the role of MHC class II A and E genes in autoimmune susceptibility in murine lupus models with intragenic recombination.

    PubMed

    Zhang, Danqing; Fujio, Keishi; Jiang, Yi; Zhao, Jingyuan; Tada, Norihiro; Sudo, Katsuko; Tsurui, Hiromichi; Nakamura, Kazuhiro; Yamamoto, Kazuhiko; Nishimura, Hiroyuki; Shira, Toshikazu; Hirose, Sachiko

    2004-09-21

    Systemic lupus erythematosus (SLE) is a multigenic autoimmune disease, and the major histocompatibility complex (MHC) class II polymorphism serves as a key genetic element. In SLE-prone (NZB x NZW)F(1) mice, the MHC H-2(d/z) heterozygosity (H-2(d) of NZB and H-2(z) of NZW) has a strong impact on disease; thus, congenic H-2(d/d) homozygous F(1) mice do not develop severe disease. In this study, we used Ea-deficient intra-H-2 recombination to establish A(d/d)-congenic (NZB x NZW)F(1) mice, with or without E molecule expression, and dissected the role of class II A and E molecules. Here we found that A(d/d) homozygous F(1) mice lacking E molecules developed severe SLE similar to that seen in wild-type F1 mice, including lupus nephritis, autoantibody production, and spontaneously occurring T cell activation. Additional evidence revealed that E molecules prevent the disease in a dose-dependent manner; however, the effect is greatly influenced by the haplotype of A molecules, because wild-type H-2(d/z) F(1) mice develop SLE, despite E molecule expression. Studies on the potential of dendritic cells to present a self-antigen chromatin indicated that dendritic cells from wild-type F(1) mice induced a greater response of chromatin-specific T cells than did those from A(d/d) F(1) mice, irrespective of the presence or absence of E molecules, suggesting that the self-antigen presentation is mediated by A, but not by E, molecules. Our mouse models are useful for analyzing the molecular mechanisms by which MHC class II regions regulate the process of autoimmune responses. PMID:15361580

  11. Renal failure due to granulomatous interstitial nephritis in native and allograft renal biopsies: experience from a tertiary care hospital.

    PubMed

    Gupta, Pallav; Rana, D S; Bhalla, A K; Gupta, Ashwini; Malik, Manish; Gupta, Anurag; Bhargava, Vinant

    2014-10-01

    Granulomatous interstitial nephritis is a rare cause of renal failure in both native and allograft renal biopsies. Drugs and sarcoidosis are the commonest causes of granulomatous interstitial nephritis as reported in Western countries. Unlike the west, tuberculosis is the commonest cause of granulomatous interstitial nephritis in Indian subcontinent. The etiological factors, clinical course, glomerular and tubulointerstitial changes associated with granulomatous interstitial nephritis have been analyzed in the present study along with the outcome in patients with granulomatous interstitial nephritis. PMID:25155448

  12. The Effect of Mycophenolate Mofetil on Disease Development in the gld.apoE−/− Mouse Model of Accelerated Atherosclerosis and Systemic Lupus Erythematosus

    PubMed Central

    Richez, Christophe; Richards, Rocco J.; Duffau, Pierre; Weitzner, Zachary; Andry, Christopher D.; Rifkin, Ian R.; Aprahamian, Tamar

    2013-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by autoantibody production and inflammatory disease involving multiple organs. Premature atherosclerosis is a common complication of SLE and results in substantial morbidity and mortality from cardiovascular disease (CVD). The reasons for the premature atherosclerosis in SLE are incompletely understood, although chronic inflammation is thought to play an important role. There is currently no known preventative treatment of premature atherosclerosis in SLE. Mycophenolate mofetil (MMF) is an immunosuppressive agent that is commonly used for treatment of patients with SLE. In order to study the impact of this drug on murine lupus disease including premature atherosclerosis development, we treated gld.apoE−/− mice, a model of SLE and accelerated atherosclerosis, with MMF. We maintained seven-week old gld.apoE−/− mice on a high cholesterol Western diet with or without MMF. After 12 weeks on diet, mice receiving MMF showed decreased atherosclerotic lesion area compared to the control group. MMF treatment also improved the lupus phenotype, indicated by a significant decrease circulating autoantibody levels and ameliorating lupus nephritis associated with this model. This data suggests that the effects of MMF on the immune system may not only be beneficial for lupus, but also for inflammation driving lupus-associated atherosclerosis. PMID:23577189

  13. Cutaneous Lupus Erythematosus: Diagnosis and treatment

    PubMed Central

    Okon, Lauren G.; Werth, Victoria P.

    2013-01-01

    Cutaneous lupus erythematosus encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several subtypes, including acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus. Chronic cutaneous lupus erythematosus includes discoid lupus erythematosus, lupus erythematosus profundus, chilblain cutaneous lupus, and lupus tumidus. Diagnosis of these diseases requires proper classification of the subtype, through a combination of physical exam, laboratory studies, histology, antibody serology, and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. Treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring, or treatment-refractory disease. In this review, we discuss issues in classification and diagnosis of the various subtypes of CLE, as well as provide an update on therapeutic management. PMID:24238695

  14. Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management.

    PubMed

    Lam, Nguyet-Cam Vu; Ghetu, Maria V; Bieniek, Marzena L

    2016-08-15

    Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treatment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body systems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient's family physician to improve chronic care as well as preventive health services. PMID:27548593

  15. 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

  16. Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study

    PubMed Central

    Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Ordi-Ros, Josep; Balada, Eva; Bijl, Marc; Papasteriades, Chryssa; Carreira, Patricia; Skopouli, Fotini N.; Witte, Torsten; Endreffy, Emöke; Marchini, Maurizio; Migliaresi, Sergio; Sebastiani, Gian Domenico; Santos, Maria Jose; Suarez, Ana; Blanco, Francisco J.; Barizzone, Nadia; Pullmann, Rudolf; Ruzickova, Sarka; Lauwerys, Bernard R.; Gomez-Reino, Juan J.; Gonzalez, Antonio

    2012-01-01

    Introduction Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. Methods European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. Results There were three new associations: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30, Pcorr = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. Conclusion Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component. PMID:23049788

  17. Apoptosis in chronic cutaneous lupus erythematosus, discoid lupus, and lupus profundus

    PubMed Central

    Sáenz-Corral, Claudia Ileana; Vega-Memíje, María Elisa; Martínez-Luna, Eduwiges; Cuevas-González, Juan Carlos; Rodríguez-Carreón, Alma Angélica; de la Rosa, Juan José Bollain-y-Goytia; del Muro, Felipe de Jesús Torres; Avalos-Díaz, Esperanza

    2015-01-01

    Introduction: Lupus erythematosus is a multisystemic disease that is characterized by autoantibody production and immune complex deposition in such tissues as the mucosa, joints, the central nervous system, and skin. Cutaneous lupus erythematosus is categorized as acute, subacute, and chronic. Chronic cutaneous lupus erythematosus comprises discoid lupus erythematosus (DLE) and lupus profundus (LP). Aim: To analyze the expression of proapoptotic molecules in patients with lupus erythematosus discoid and lupus profundus. Material and methods: Descriptive study, the study groups comprised 10 cases of LP and 10 cases of DLE, and a control. Skin samples of cases and controls were processed for immunohistochemistry and by TUNEL technique. The database and statistical analysis was performed (statistical test X2) SPSS (Chicago, IL, USA). Results: Apoptotic features were broadly distributed along the skin biopsies in epidermal keratinocytes as well as at dermis. By immunohistochemistry the expression of Fas receptor and Fas-L was higher in the skin of lupus patients compared with controls. We also noted differences in Fas-L, -Fas, and -Bax proteins expression intensity in discoid lupus erythematosus patients in the epidermis, and hair follicles. Conclusions: Fas and Fas-L are expressed similarly in LP and DLE. PMID:26261624

  18. Role of interleukin-1 in mesangial cell proliferation and matrix deposition in experimental mesangioproliferative nephritis.

    PubMed Central

    Tesch, G. H.; Lan, H. Y.; Atkins, R. C.; Nikolic-Paterson, D. J.

    1997-01-01

    We examined the functional role of interleukin (IL)-1 in mesangial cell proliferation during rat anti-Thy-1 nephritis by blocking its action with IL-1 receptor antagonist (IL-1ra). Anti-Thy-1 nephritis was induced by intravenous injection of 5 mg/kg OX-7 IgG (day 0) into inbred Wistar rats. Groups of animals (n = 9) were implanted with a micro-osmotic pump on day -1, which delivered 25 micrograms/hour human recombinant IL-1ra or saline continuously until the rats were killed at day 6, the peak of mesangial cell proliferation. Immunostaining showed that IL-1 was expressed by mesangial cells during disease. IL-1ra treatment did not affect the mild, but significant, proteinuria seen after OX-7 injection. Compared with saline treatment, IL-1ra treatment reduced mesangial cell proliferation (decreases 24% P < 0.05), glomerular hypercellularity (decreases 29%; P < 0.05), and glomerular macrophage accumulation (decreases 20%; P < 0.05). However, IL-1ra treatment had no effect on glomerular IL-1 beta mRNA expression and caused only a small reduction in the high levels of glomerular expression of platelet-derived growth factor-beta protein (decreases 6%; P < 0.05). IL-1ra caused a modest reduction in the marked up-regulation of glomerular transforming growth factor-beta 1 mRNA expression on day 6 (decreases 26%; P < 0.05), although urinary excretion of this factor was unaffected. Interestingly, IL-1ra treatment had relatively little effect upon glomerular deposition of laminin, fibronectin, and collagen type IV seen in this acute disease. In conclusion, this study has 1) demonstrated that IL-1 is expressed by mesangial cells in vivo, 2) demonstrated that IL-1 is a mesangial cell growth factor in experimental mesangioproliferative nephritis, and 3) suggests that IL-1 has little or no fibrogenic activity in mesangial matrix deposition. Images Figure 1 Figure 5 PMID:9212740

  19. Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus.

    PubMed

    Masek-Hammerman, K; Peeva, E; Ahmad, A; Menon, S; Afsharvand, M; Peng Qu, R; Cheng, J B; Syed, J; Zhan, Y; O'Neil, S P; Pleasic-Williams, S; Cox, L A; Beidler, D

    2016-02-01

    This study's objective was to assess the effects of PD-0360324, a fully human immunoglobulin G2 monoclonal antibody against macrophage colony-stimulating factor in cutaneous lupus erythematosus (CLE). Patients with active subacute CLE or discoid lupus erythematosus were randomized to receive 100 or 150 mg PD-0360324 or placebo via intravenous infusion every 2 weeks for 3 months. Blood and urine samples were obtained pre- and post-treatment to analyse pharmacokinetics and pharmacodynamic changes in CD14(+) CD16(+) monocytes, urinary N-terminal telopeptide (uNTX), alanine/aspartate aminotransferases (ALT/AST) and creatine kinase (CK); tissue biopsy samples were taken to evaluate macrophage populations and T cells using immunohistochemistry. Clinical efficacy assessments included the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Among 28 randomized/analysed patients, peak/trough plasma concentrations increased in a greater-than-dose-proportional manner with dose increases from 100 to 150 mg. Statistically significant differences were observed between active treatment and placebo groups in changes from baseline in CD14(+) CD16(+) cells, uNTX, ALT, AST and CK levels at most time-points. The numbers, density and activation states of tissue macrophages and T cells did not change from baseline to treatment end. No between-group differences were seen in CLASI. Patients receiving PD-0360324 reported significantly more adverse events than those receiving placebo, but no serious adverse events. In patients with CLE, 100 and 150 mg PD-0360324 every 2 weeks for 3 months suppressed a subset of circulating monocytes and altered activity of some tissue macrophages without affecting cell populations in CLE skin lesions or improving clinical end-points. PMID:26376111

  20. An acquired defect in IgG-dependent phagocytosis explains the impairment in antibody-mediated cellular depletion in Lupus.

    PubMed

    Ahuja, Anupama; Teichmann, Lino L; Wang, Haowei; Dunn, Robert; Kehry, Marilyn R; Shlomchik, Mark J

    2011-10-01

    B cells play important roles in autoimmune diseases ranging from multiple sclerosis to rheumatoid arthritis. B cells have also long been considered central players in systemic lupus erythematosus. However, anti-CD20-mediated B cell depletion was not effective in two clinical lupus studies, whereas anti-B lymphocyte stimulator, which inhibits B cell survival, was effective. Others and we previously found that anti-CD20-based depletion was surprisingly ineffective in tissues of lupus-prone mice, but that persistent high doses eventually led to depletion and ameliorated lupus. Lupus patients might also have incomplete depletion, as suggested in several studies, and which could have led to therapeutic failure. In this study, we investigated the mechanism of resistance to Ab-mediated cellular depletion in murine lupus. B cells from lupus-prone mice were easily depleted when transferred into normal environments or in lupus-prone mice that lacked serum Ig. Serum from lupus-prone mice transferred depletion resistance, with the active component being IgG. Because depletion is FcγR-dependent, we assayed macrophages and neutrophils exposed to lupus mouse serum, showing that they are impaired in IgG-mediated phagocytosis. We conclude that depletion resistance is an acquired, reversible phagocytic defect depending on exposure to lupus serum IgG. These results have implications for optimizing and monitoring cellular depletion therapy. PMID:21873531

  1. THE CAROLINA LUPUS STUDY (CLU)

    EPA Science Inventory

    Carolina Lupus (CLU) Study, an epidemiologic study of risk factors for systemic lupus erythematosus (SLE). SLE is a severe, chronic, systemic autoimmune disease that disproportionately affects women and African-Americans. The CLU Study focuses on measures of endogenous hormone ex...

  2. Lupus - the cold, hard facts.

    PubMed

    Wong, N W K; Ng, Vt-Y; Ibrahim, S; Slessarev, M; Chandran, V

    2014-07-01

    Systemic lupus erythematosus (SLE) is a multisystem chronic disease with a multitude of clinical presentations. We review and synthesize how an environmental insult (exposure to extreme cold for a short duration) and endogenous (antiphospholipid antibody syndrome, SLE vasculitis) insults in a susceptible young female with lupus (peripheral arterial disease, smoking, SLE) led to a perfect storm resulting in catastrophic injuries (frostbite). PMID:24699313

  3. Toward the Development of a Lupus Interactive Navigator to Facilitate Patients and Their Health Care Providers in the Management of Lupus: Results of Web-Based Surveys

    PubMed Central

    Neville, Carolyn; DaCosta, Deborah; Rochon, Murray; Eng, Davy

    2014-01-01

    Background Systemic lupus erythematosus is an inflammatory autoimmune disease associated with high morbidity and unacceptable mortality. Information and management tools are needed to help persons with lupus cope with their illness and facilitate health care providers in the delivery of care. Objective The objective of the study was to assess the needs and find solutions to support persons with lupus and their health care providers. Methods Web-based surveys were distributed across Canada to persons with lupus and their relatives (n=3119), rheumatologists (n=517), and arthritis health professionals (AHPs) (n=226) by Lupus Canada, the Canadian Rheumatology Association, and the Arthritis Health Professions Association, respectively. Results The survey sample comprised 665 (21.3%) persons with lupus, 98 (19.0%) rheumatologists, and 74 (32.7%) AHPs. Among the participants with lupus, 92.4% were female, the average age was 46.8 (SD 12.7) years, 79.2% were Caucasian, and 58.8% were employed. All Canadian provinces and territories were represented. The majority (43.3%) of respondents were from Ontario. Mean disease duration was 10.2 (SD 9.5) years, and 41.9% rated their global assessment as fair or poor. There was high agreement between lupus participants and health care providers regarding disease-specific information topics. All groups rated topics related to lupus, fatigue, medications, and stress as most important. Ratings differed among lupus participants and their health care providers regarding perceived helpfulness of some of the patient tools, such as the option to view test results. Needs differed for persons with lupus based on age, sex, depression, stress, and disease activity. Differences in health care provider needs were based on amount of experience in treating lupus. Conclusions Information and support tools needed for persons with lupus and their health care providers were identified. These results will help guide us in the development of a Web

  4. Mortality from nephritis and nephrosis in the fibreglass manufacturing industry

    PubMed Central

    Chiazze, L.; Watkins, D. K.; Fryar, C.; Fayerweather, W.; Bender, J. R.; Chiazze, M.

    1999-01-01

    OBJECTIVES: To investigate the question of whether there is an association between exposure to silica or respirable glass fibre and mortality from nephritis or nephrosis among workers in fibrous glass wool manufacturing facilities. METHODS: A case-control study with cases and controls derived from the Owens Corning mortality surveillance system. Two case-control analyses were carried out, one where the cases are defined with nephritis or nephrosis as the underlying cause of death and one where cases are defined as those where nephritis or nephrosis is either the underlying or a contributing cause of death. RESULTS: There is no consistent relation between respirable fibres or respirable silica and nephritis or nephrosis when the analysis is based either on underlying cause only or on underlying plus contributing cause of death. None of the sociodemographic variables considered suggests an increased risk when considering both underlying and contributing cause of death. CONCLUSIONS: These data would seem to support the contention that the most accurate picture of renal disease will be gained from the use of all information on the death certificate and not only the underlying cause. For these data, all odds ratios (ORs) for respirable fibres and silica based on both underlying and contributing cause of death are < 1 with the exception of the highest exposure to silica which is slightly > 1 (OR = 1.04). Although these results do not prove that there is no association between nephritis and nephrosis and exposure to fibreglass or silica in the fibreglass manufacturing environment, they do not support the assertion that such an association exists.   PMID:10448324

  5. 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

  6. 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

  7. 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

  8. Dominant NZB contributions to lupus in the (SWR x NZB)F1 model.

    PubMed

    Xie, S; Chang, S H; Sedrak, P; Kaliyaperumal, A; Datta, S K; Mohan, C

    2002-10-01

    (SWR x NZB)F1 (or SNF1) mice succumb to lupus nephritis. Analysis of NZB x SNF1 backcross mice has recently revealed the existence of four dominant SWR loci (H2 on Chr 17, Swrl-1 on Chr 1, Swrl-2 on Chr 14 and Swrl-3 on Chr 18), and two NZB loci (Nba1 and Lbw2/Sbw2, both on Chr 4) conferring lupus susceptibility. The present study focusing on a panel of 88 SWR x SNF1 backcross mice reveals the existence of five suggestive loci for antinuclear antibody formation, consisting of three dominant NZB contributions (Nba4 on Chr 5, Lbw4 on Chr 6, and Nba5 on Chr 7), and two recessive SWR contributions (Swrl-1 on Chr 1, and Swrl-4 on Chr 10). In addition, this study reveals a dominant NZB locus for GN (Nba3 on Chr 7, peak at 31 cM), and a dominant NZB locus linked to early mortality, on Chr 10 (peak at 4 cM). Collectively, these studies suggest that lupus in the SNF1 strain is the epistatic end-product of four dominant SWR loci and four dominant NZB loci. The immunological functions and molecular identities of these loci await elucidation. PMID:12215897

  9. The TLR7 7926A>G polymorphism is associated with susceptibility to systemic lupus erythematosus.

    PubMed

    Tian, Jing; Ma, Yan; Li, Jing; Cen, Han; Wang, De-Guang; Feng, Chen-Chen; Li, Ruo-Jie; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

    2012-07-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder that predominantly affects women of childbearing age, with a female-to-male ratio of approximately 9:1. Previous findings indicated that male cases of SLE were associated with Klinefelter's syndrome (47, XXY), whereas females with Turner's syndrome (45, X0) did not contract SLE. Additionally, duplicated Toll-like receptor 7 (TLR7) was found to promote lupus-like disease. Consequently, the aim of this study was to evaluate whether the TLR7 gene served as a genetic marker for the development of SLE. A case-control study was performed on one tag single nucleotide polymorphism TLR7 rs1634323 in a population with 507 SLE patients and 513 healthy controls. Genotyping was determined by the TaqMan genotyping assay using the ABI 7300 real-time reverse transcription polymerase chain reaction system. The results showed a significantly elevated risk of SLE with the rs1634323 AG genotype in females (P = 0.040, OR = 1.897, 95% CI 1.031-3.491), whereas a similar association was not replicated in males (P = 0.303, OR = 0.338, 95% CI 0.043-2.656). In a subgroup analysis by clinical manifestation of lupus nephritis, no significant differences were found. These findings indicate that the TLR7 gene rs1634323 polymorphism may contribute to SLE susceptibility in females. PMID:22505023

  10. An uncommon presentation of an uncommon disease: relapsing polychondritis overlap with systemic lupus erythematosus.

    PubMed

    Nguyen, Michelle A; Rahnama-Moghadam, Sahand; Gilson, Robert T

    2016-01-01

    Relapsing polychondritis (RP) is a rare rheumatologic disorder in which recurrent episodes of inflammation result in destruction of cartilage of the ears and nose. The joints, eyes, audio-vestibular system, heart valves, respiratory tract, kidneys, and skin can also be involved. Skin involvement is most frequently linked to concomitant myelodysplastic syndrome and has rarely been associated with systemic lupus erythematosus. A 47-year-old woman presented with violaceous, indurated, tender plaques on the bilateral cartilaginous ears with sparing of the lobes, consistent with RP. Further investigations revealed positive ANA and anti-Smith antibody, oral ulcers, a photo-distributed skin eruption, and biopsy-proven lupus nephritis, leading to a second concomitant diagnosis of systemic lupus erythematosus (SLE). The diagnosis of SLE associated with RP was made and the patient was started on oral prednisone and hydroxychloroquine. This is a rare report of SLE associated with RP. It is unclear whether RP occurring in patients with SLE represents another clinical manifestation of SLE or a coexisting disease. However, a significant ANA titer in a patient with RP strongly suggests the presence of an associated autoimmune disorder. If immunologic abnormalities usually found in SLE are detected in patients with RP, it is important to monitor patients for the development of other manifestations of SLE. PMID:27267190

  11. Asymptomatic diffuse "encephalitic" cerebral toxoplasmosis in a woman with systemic lupus erythematosus.

    PubMed

    Murro, Diana; Novo, Jorge; Arvanitis, Leonidas

    2016-07-01

    Classic cerebral toxoplasmosis typically presents with neurologic symptoms such as seizures and mental status changes and histological examination shows focal lesions with necrosis. However, in the diffuse "encephalitic" form, patients are asymptomatic with diffuse, inflammatory, non-necrotic lesions. Asymptomatic diffuse "encephalitic" toxoplasmosis has been reported only in four acquired immunodeficiency syndrome patients and one human immunodeficiency virus (HIV) negative patient with chronic lymphocytic leukemia. We present a 36-year-old HIV-negative woman with systemic lupus erythematosus and lupus nephritis who was on immunosuppression for 9years after cadaveric renal transplant and died from pulmonary hemorrhage and cytomegalovirus pneumonia. Brain autopsy findings revealed multifocal microglial nodules containing Toxoplasma bradyzoites and associated astrogliosis. These nodules were prominent in the cerebellum, midbrain and medulla and also present in the cortex and thalamus. No coagulative necrosis, necrotizing abscesses, or other opportunistic infections were present. The patient had previously exhibited no neurologic symptoms and there was no clinical suspicion for toxoplasmosis. To the best of our knowledge, this is the first case of diffuse, non-necrotizing, "encephalitic" cerebral toxoplasmosis reported in a lupus patient and also the first reported female case. PMID:26896909

  12. Lupus thrombocytopenia: clinical implications and prognostic significance

    PubMed Central

    Ziakas, P; Giannouli, S; Zintzaras, E; Tzioufas, A; Voulgarelis, M

    2005-01-01

    Methods: 632 patients were reviewed retrospectively. Fifty patients with thrombocytopenia were included as cases and matched with 100 control patients. Clinical manifestations at first thrombocytopenic episode were recorded. Classification criteria at diagnosis, basic immunological profiles, disease activity (ECLAM), and end organ damage (SLICC) were recorded. Results: 29/50 (58%) had thrombocytopenia at diagnosis of lupus. Haemorrhagic manifestations were associated with the degree of thrombocytopenia (p<0.001). Anticardiolipin antibodies were not related to the degree of thrombocytopenia or the severity of haemorrhagic manifestations. Megakaryocytes were normal or increased in 26/28 (93%) bone marrow specimens, indicating peripheral platelet destruction. Patients with high disease activity were more thrombocytopenic than controls (OR = 2.61, 95% CI 1.13 to 5.96, p = 0.009). Patients with low C3 or CH50 were more likely to be thrombocytopenic (OR = 2.36, 95% CI 1.05 to 5.26, p = 0.029). Median SLICC for lupus patients with thrombocytopenia was 2 (range 0–11) compared with 1 (range 0–12) for controls (p<0.001). No deaths occurred during thrombocytopenic episodes. Conclusions: Thrombocytopenia is not directly associated with end organ damage and mortality, but defines a subgroup of patients with higher morbidity and is thus a major complication of systemic lupus erythematosus, affecting overall prognosis. PMID:16100344

  13. 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

  14. 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

  15. Successful treatment of severe hantavirus nephritis with corticosteroids: a case report and literature review.

    PubMed

    Martinuč Bergoč, Maja; Lindič, Jelka; Kovač, Damjan; Ferluga, Dušan; Pajek, Jernej

    2013-08-01

    Hantaviruses can be associated with severe form of hemorrhagic fever with renal syndrome although there are only a few cases reporting chronic kidney disease after hantavirus infection. We report a severe nonresolving chronic renal failure after protracted Dobrava hantavirus infection successfully treated with corticosteroids. Ten days after working in a basement a 33-year-old man fell seriously ill, with high fever, chills, diffuse myalgia, headache and abdominal pain. After hospital admission a diagnosis of hemorrhagic fever with renal syndrome caused by Dobrava hantavirus was made. Acute oliguric kidney injury developed in the first 3 days after admission, in a few days diuresis restored and he became polyuric. Nevertheless renal failure persisted and he needed hemodialysis. Because of nonresolving kidney failure, nephrogenic diabetes insipidus and renoparenchymal arterial hypertension persisting 2 months after onset of symptoms, a kidney biopsy was performed, showing severe necrotizing tubulointerstitial nephritis. High dose methylprednisolone therapy was started and his renal function significantly improved. Two months later a second renal biopsy showed persisting elements of active necrotizing tubulointerstitial nephritis. We decided to stop corticosteroid treatment and introduced aldosterone antagonist eplerenon as anti-fibrotic agent, and his renal function further improved and remained stable. Nine months later his serum creatinine concentration was 227 μmol/L, proteinuria 0.156 g/day and well controlled nephrogenic diabetes insipidus. PMID:23931879

  16. Interstitial nephritis caused by HIV infection by itself: a case report

    PubMed Central

    Doi, Asako; Iwata, Kentaro; Hara, Shigeo; Imai, Yukihiro; Hasuike, Toshikazu; Nishioka, Hiroaki

    2016-01-01

    Interstitial nephritis is a common cause of renal dysfunction. It is primarily caused by drugs, infections, or autoimmune disorders. Patients with human immunodeficiency virus (HIV) infection can develop interstitial nephritis, although it typically occurs because of the aforementioned etiologies and not as a direct consequence of HIV infection. Interstitial lesions may occur in patients with HIV-associated nephropathy (HIVAN). However, interstitial nephritis without the glomerular injuries characteristic of HIVAN, and without the risk factors described earlier, is very rare. Here, we describe a rare case of interstitial nephritis that was likely caused directly by HIV infection and not by other etiologies. PMID:27621665

  17. Interstitial nephritis caused by HIV infection by itself: a case report.

    PubMed

    Doi, Asako; Iwata, Kentaro; Hara, Shigeo; Imai, Yukihiro; Hasuike, Toshikazu; Nishioka, Hiroaki

    2016-01-01

    Interstitial nephritis is a common cause of renal dysfunction. It is primarily caused by drugs, infections, or autoimmune disorders. Patients with human immunodeficiency virus (HIV) infection can develop interstitial nephritis, although it typically occurs because of the aforementioned etiologies and not as a direct consequence of HIV infection. Interstitial lesions may occur in patients with HIV-associated nephropathy (HIVAN). However, interstitial nephritis without the glomerular injuries characteristic of HIVAN, and without the risk factors described earlier, is very rare. Here, we describe a rare case of interstitial nephritis that was likely caused directly by HIV infection and not by other etiologies. PMID:27621665

  18. Beyond Apoptosis in Lupus

    PubMed Central

    Colonna, Lucrezia; Lood, Christian; Elkon, Keith B.

    2014-01-01

    Purpose of review Systemic lupus erythematosus (SLE) is characterized by autoantibodies directed against nuclear autoantigens normally concealed from immune recognition in healthy individuals. Here we summarize recently identified mechanisms of abnormal cell death leading to exposure and aberrant processing of nucleoprotein self antigens, and discuss their role in the SLE pathogenesis. Recent findings During the past few years, the unveiling of several new forms of cell death has expanded our understanding beyond the simple view of “apoptotic” versus “necrotic” cell death. SLE patients show abnormalities in cell death at several levels, including increased rates of apoptosis, necrosis, and autophagy, as well as reduced clearance of dying cells. These abnormalities lead to an increased autoantigen burden and also antigen modifications, such as nucleic acid oxidation that increase the inflammatory properties of self antigens. Recent investigations have highlighted the role of opsonins in determining the immunogenic versus tolerogenic characteristics of self antigens. Summary Dysregulation of different forms of programmed cell death contributes to increased exposure, availability, and immunogenic characteristic of intracellular self antigens, which all participate in development of lupus autoimmunity. As our understanding of abnormalities of cell death in SLE advances, potential therapeutic opportunities await human implementation. PMID:25036095

  19. 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 aim of this study was to evaluate changes in the cytokines INF-γ, IL-10, IL-6, TNF-α and soluble TNF receptors (sTNFR1 and sTNFR2) in response to single bouts of acute moderate and intense exercise in systemic lupus erythematosus women with active (SLE(ACTIVE)) and inactive (SLE(INACTIVE)) disease. Twelve SLE(INACTIVE) women (age: 35.3 ± 5.7 yrs; BMI: 25.6±3.4 kg/m2), eleven SLE(ACTIVE) women (age: 30.4 ± 4.5 yrs; BMI: 26.1±4.8 kg/m2), and 10 age- and BMI-matched healthy control women (HC) performed 30 minutes of acute moderate (~50% of VO(2)peak) and intense (~70% of VO(2)peak) exercise bout. Cytokines and soluble TNF receptors were assessed at baseline, immediately after, every 30 minutes up to three hours, and 24 hours after both acute exercise bouts. In response to acute moderate exercise, cytokines and soluble TNF receptors levels remained unchanged in all groups (P>0.05), except for a reduction in IL-6 levels in the SLE(ACTIVE) group at the 60th and 180th minutes of recovery (P<0.05), and a reduction in sTNFR1 levels in the HC group at the 90th, 120th, 150th, 180th minutes of recovery (P<0.05). The SLE(INACTIVE) group showed higher levels of TNF-α, sTNFR1, and sTNFR2 at all time points when compared with the HC group (P<0.05). Also, the SLE(ACTIVE) group showed higher levels of IL-6 at the 60th minute of recovery (P<0.05) when compared with the HC group. After intense exercise, sTNFR1 levels were reduced at the 150th (P=0.041) and 180th (P=0.034) minutes of recovery in the SLE(INACTIVE) group, whereas the other cytokines and sTNFR2 levels remained unchanged (P>0.05). In the HC group, IL-10, TNF-α, sTNFR1, and sTNFR2 levels did not change, whilst INF-γ levels decreased (P=0.05) and IL-6 levels increased immediately after the exercise (P=0.028), returning to baseline levels 24 hours later (P > 0.05). When compared with the HC group, the SLE(INACTIVE) group showed higher levels of TNF-α and sTNFR2 in all time points, and higher levels of sTNFR1 at

  20. An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis.

    PubMed

    Ramírez-Sandoval, Roxana; Luévano-Rodríguez, Nayeli; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Saldívar-Elias, Sergio; Gurrola-Carlos, Reinaldo; Avalos-Díaz, Esperanza; Bollain-y-Goytia, Juan José; Herrera-Esparza, Rafael

    2015-01-01

    Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis. PMID:26064998

  1. An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis

    PubMed Central

    Ramírez-Sandoval, Roxana; Luévano-Rodríguez, Nayeli; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Saldívar-Elias, Sergio; Gurrola-Carlos, Reinaldo; Avalos-Díaz, Esperanza; Bollain-y-Goytia, Juan José

    2015-01-01

    Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis. PMID:26064998

  2. Variables associated to fetal microchimerism in systemic lupus erythematosus patients.

    PubMed

    da Silva Florim, Greiciane Maria; Caldas, Heloisa Cristina; Pavarino, Erika Cristina; Bertollo, Eny Maria Goloni; Fernandes, Ida Maria Maximina; Abbud-Filho, Mario

    2016-01-01

    In the present study, we sought to identify the factors during the pregnancy of systemic lupus erythematosus (SLE) patients that could be linked to the presence and proliferation of male fetal cells (MFC) and the possible relation between these factors and development of lupus nephritis (LN). We evaluated 18 healthy women (control group) and 28 women affected by SLE. Genomic DNA was extracted from peripheral blood and quantified using the technique of quantitative real-time polymerase chain reaction (qPCR) for specific Y chromosome sequences. The amount of MFC was significantly higher in the SLE group compared with the controls (SLE 252 ± 654 vs control 2.13 ± 3.7; P = 0.029). A higher amount of MFC was detected among multiparous SLE patients when compared with the control group (SLE 382 ± 924 vs control 0.073 ± 0.045; P = 0.019). LN was associated with reduced amount of MFC (LN 95.5 ± 338 vs control 388 ± 827; P = 0.019) especially when they have delivered their child before age 18 (LN 0.23 ± 0.22 vs control 355 ± 623; P = 0.028). SLE patients present a higher amount of MFC, which may increase with the time since birth of the first male child. LN patients showed an inverse correlation with MFC, suggesting that the role of the cells may be ambiguous during the various stages of development of the disease. PMID:26608904

  3. Ergotamine-induced acute tubulo-interstitial nephritis.

    PubMed

    Pakfetrat, Maryam; Rasekhi, Akbar; Eftekhari, Fatemeh; Hashemi, Nahid; Roozbeh, Jamshid; Torabineghad, Simin; Malekmakan, Leila

    2013-09-01

    Ergotamine has been used for the treatment of migraine for many years, and its use in adults is considered to be safe and effective. In this report, we present a 22-year-old female patient, a known case of migraine, who was on ergotamine tartrate and presented with hypertension and renal failure. Renal biopsy indicated features of acute tubulo-interstitital nephritis. PMID:24029265

  4. Vitamin D and Systemic Lupus Erythematosus: Myth or Reality?

    PubMed

    Watad, Abdulla; Neumann, Shana G; Soriano, Alessandra; Amital, Howard; Shoenfeld, Yehuda

    2016-01-01

    There is growing interest in the contribution of vitamin D deficiency to autoimmunity. Several studies have shown an association between low levels of vitamin D and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid diseases, celiac disease, and systemic lupus erythematosus (SLE). Vitamin D receptor ligands can mediate immunosuppressive effects. It has been suggested that low levels of this hormone contribute to the immune activation in lupus and other autoimmune diseases. This review updates and summarizes the literature on the association between vitamin D and SLE, and discusses the various correlations between vitamin D and SLE activity, clinical expressions, serology, and gene polymorphisms of vitamin D receptors. PMID:27228639

  5. IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis

    PubMed Central

    Watkins, Amanda A.; Yasuda, Kei; Wilson, Gabriella E.; Aprahamian, Tamar; Xie, Yao; Maganto-Garcia, Elena; Shukla, Prachi; Oberlander, Lillian; Laskow, Bari; Menn-Josephy, Hanni; Wu, Yuanyuan; Duffau, Pierre; Fried, Susan K.; Lichtman, Andrew H.; Bonegio, Ramon G.; Rifkin, Ian R.

    2015-01-01

    Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. Here we addressed this question using the gld.apoE−/− mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and non-immune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients. PMID:25595782

  6. Lupus Erythematosus Panniculitis in Pregnancy

    PubMed Central

    Gondane, Swati; Kothiwala, Rajkumar; Dangi, Sapna; Meherda, Ashok

    2015-01-01

    A case of lupus erythematosus (LE) panniculitis in pregnancy without any lesions of discoid LE or systemic LE is being reported. There were no systemic symptoms. Her ANA, anti-dsDNA, anti-Ro/SSA, and anti-La/SSB antibodies were within normal limits. Diagnosis of lupus panniculitis was considered on clinical and histopathological grounds. The condition responded favorably to systemic steroid therapy. PMID:26677307

  7. IL-10 regulates murine lupus.

    PubMed

    Yin, Zhinan; Bahtiyar, Gul; Zhang, Na; Liu, Lanzhen; Zhu, Ping; Robert, Marie E; McNiff, Jennifer; Madaio, Michael P; Craft, Joe

    2002-08-15

    MRL/MpJ-Tnfrsf6(lpr) (MRL/MpJ-Fas(lpr); MRL-Fas(lpr)) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10(-/-)) MRL-Fas(lpr) (MRL-Fas(lpr) IL-10(-/-)) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Fas(lpr) IL-10(+/-) and MRL-Fas(lpr) IL-10(+/+) mice, respectively). MRL-Fas(lpr) IL-10(-/-) mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Fas(lpr) IL-10(-/-) mice was closely associated with enhanced IFN-gamma production by both CD4(+) and CD8(+) cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Fas(lpr) animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus. PMID:12165544

  8. Leukocyte Beta-Catenin Expression Is Disturbed in Systemic Lupus Erythematosus.

    PubMed

    Orme, Jacob J; Du, Yong; Vanarsa, Kamala; Wu, Tianfu; Satterthwaite, Anne B; Mohan, Chandra

    2016-01-01

    Wnt/β-catenin signaling is relatively understudied in immunity and autoimmunity. β-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished β-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/β-catenin, were also decreased in lupus-prone mice. Surprisingly, however, preemptive deletion of β-catenin from macrophages appears to have no effect on lupus development, even in mice with varying genetic loads for lupus. Although myeloid-specific loss of β-catenin does not seem to be important for lupus development, the potential role of this transcription factor in other leukocytes and renal cells remain to be elucidated. PMID:27548498

  9. Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells

    PubMed Central

    Reihl, Alec M.

    2016-01-01

    Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with multiple tissue manifestations. In this review, we summarize recent studies on the roles of conventional DC and plasmacytoid DC in the development of both murine lupus and human SLE. In the past decade, studies using selective DC depletions have demonstrated critical roles of DC in lupus progression. Comprehensive in vitro and in vivo studies suggest activation of DC by self-antigens in lupus pathogenesis, followed by breakdown of immune tolerance to self. Potential treatment strategies targeting DC have been developed. However, many questions remain regarding the mechanisms by which DC modulate lupus pathogenesis that require further investigations. PMID:27034965

  10. Leukocyte Beta-Catenin Expression Is Disturbed in Systemic Lupus Erythematosus

    PubMed Central

    Orme, Jacob J.; Du, Yong; Vanarsa, Kamala; Wu, Tianfu; Satterthwaite, Anne B.

    2016-01-01

    Wnt/β-catenin signaling is relatively understudied in immunity and autoimmunity. β-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished β-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/β-catenin, were also decreased in lupus-prone mice. Surprisingly, however, preemptive deletion of β-catenin from macrophages appears to have no effect on lupus development, even in mice with varying genetic loads for lupus. Although myeloid-specific loss of β-catenin does not seem to be important for lupus development, the potential role of this transcription factor in other leukocytes and renal cells remain to be elucidated. PMID:27548498

  11. Leadership in wolf, Canis lupus, packs

    USGS Publications Warehouse

    Mech, L.D.

    2000-01-01

    I examine leadership in Wolf (Canis lupus) packs based on published observations and data gathered during summers from 1986 to 1998 studying a free-ranging pack of Wolves on Ellesmere Island that were habituated to my presence. The breeding male tended to initiate activities associated with foraging and travel, and the breeding female to initiate, and predominate in, pup care and protection. However, there was considerable overlap and interaction during these activities such that leadership could be considered a joint function. In packs with multiple breeders, quantitative information about leadership is needed.

  12. Analysis of the New Zealand Black contribution to lupus-like renal disease

    SciTech Connect

    Drake, C.G.; Rozzo, S.J.; Hirschfeld, H.F.; Smarnworawong, N.P.; Palmer, E.; Kotzin, B.L. |

    1995-03-01

    F{sub 1} progeny of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop an autoimmune process remarkably similar to human systemic lupus erythematosus. Previous studies have implicated major genetic contributions from the NZW MHC and from a dominant NZB gene on chromosome 4. To identify additional NZB contributions to lupus-like disease, (NZB x SM/J)F{sub 1} x NZW backcross mice were followed for the development of severe renal disease and were comprehensively genotyped. Despite a 50% incidence of disease significant associations between the presence of the NZB genotype and disease were noted on chromosomes 1, 4, 7, 10, 13, and 19. The data indicated that multiple NZB genes, in different combinations, contribute to severe renal disease, and that no single gene is required. To further investigate this NZB contribution, NZB x SM/J (NXSM) recombinant inbred (RI) strains were crossed with NZW mice, and F{sub 1} progeny were analyzed for the presence of lupus-like renal disease. Interestingly, nearly all of the (RI x NZW)F{sub 1} cohorts studies expressed some level of disease. Five RI strains generated a high incidence of disease, similar to (NZB x NZW)F{sub 1} mice, and nearly one-half of the cohorts developed disease at intermediate levels. Only two cohorts demonstrated very little disease, supporting the conclusion that multiple genes are capable of disease induction. Experiments correlating the genotypes of these RI strains with their ability to generate disease revealed that none of the disease-associated loci defined by the backcross analysis were present in all five RI strains that generated disease at high levels. Overall, both the backcross data and RI analysis provide additional support for the genetic complexity of lupus nephritis and uphold the conclusion that heterogeneous combinations of contributing NZB genes seem to operate in a threshold manner to generate the disease phenotype. 31 refs., 3 figs., 2 tabs.

  13. Analysis of Ancestral and Functionally Relevant CD5 Variants in Systemic Lupus Erythematosus Patients

    PubMed Central

    Consuegra, Marta; Bonet, Lizette; Carnero-Montoro, Elena; Armiger, Noelia; Caballero-Baños, Miguel; Arias, Maria Teresa; Benitez, Daniel; Ortego-Centeno, Norberto; de Ramón, Enrique; Sabio, José Mario; García–Hernández, Francisco J.; Tolosa, Carles; Suárez, Ana; González-Gay, Miguel A.; Bosch, Elena; Martín, Javier; Lozano, Francisco

    2014-01-01

    Objective CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. Methods The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. Results T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis. Conclusion The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients. PMID:25402503

  14. Early Cutaneous Lupus Erythematosus

    PubMed Central

    Sams, Wiley M.

    1966-01-01

    Cutaneous disorders which manifest themselves on the exposed parts are more likely than are hidden lesions to cause the patient to seek professional services promptly. Usually he consults his family physician or the community dermatologist. The physician who first sees the patient is dependent upon his own resources for management and diagnosis. A background of experience, a measure of energy and an inquisitive attitude are the necessary ingredients for successful management. The difficulties involved in differentiating early lupus erythematosus and polymorphic light eruptions cannot be invariably resolved even with the most complete review. The course of the disorder and the response to environmental factors supply important clues. Investigative work, especially in the field of immunology, offers hope for the solution of some of our problems. PMID:5909872

  15. Lupus, discoid on a child's face (image)

    MedlinePlus

    The round or disk shaped (discoid) rash of lupus produces red, raised patches with scales. The pores ( ... The majority (approximately 90%) of individuals with discoid lupus have only skin involvement as compared to more ...

  16. How Does Lupus Affect the Blood?

    MedlinePlus

    ... Awards Investigator Grants, Fellowships and Career Development Awards & Prizes Peer-Reviewed Grant Program LIFELINE Grant Program 2015 ... common symptoms of lupus? How can I manage my fatigue? How is lupus diagnosed? What is photosensitivity? ...

  17. Star counts in southern dark clouds: Corona Australis and Lupus.

    NASA Astrophysics Data System (ADS)

    Andreazza, C. M.; Vilas-Boas, J. W. S.

    1996-03-01

    Star counts technique is used towards southern dark globular filaments situated in the cloud complexes of Corona Australis and Lupus. Tables and maps of the distribution of visual extinction are presented for each filament. Lower limit masses for the filaments and condensations have been estimated and the central coordinates of the condensations are also given. R CrA is the most active star forming region among the filaments studied in this work whereas Lupus 1, with almost the same lower limit of mass, has only a few T Tauri stars and just one young embedded object. The distribution of direction of the magnetic field in the condensations of Lupus, suggests that the condensation morphologies does not have any apparent relation with the magnetic field orientation.

  18. Infection in systemic lupus erythematosus: friend or foe?

    PubMed Central

    Francis, Lisa; Perl, Andras

    2010-01-01

    Infectious agents have long been implicated in the pathogenesis of systemic lupus erythematosus. Common viruses, such as the Epstein-Barr virus, transfusion transmitted virus, parvovirus and cytomegalovirus, have an increased prevalence in patients with systemic lupus erythematosus. They may contribute to disease pathogenesis through triggering autoimmunity via structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self antigens or modulate antigen processing, activation, or apoptosis of B and T cells, macrophages or dendritic cells. Alternatively, some infectious agents, such as malaria, Toxoplasma gondii and Helicobacter pylori, may have a protective effect. Vaccinations may play dual roles by protecting against friend and foe alike. PMID:20209114

  19. Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a review of literature.

    PubMed

    Chiewchengchol, Direkrit; Murphy, Ruth; Edwards, Steven W; Beresford, Michael W

    2015-01-01

    Patients diagnosed with juvenile-onset systemic lupus erythematosus (JSLE) often have skin and oral lesions as part of their presentation. These mucocutaneous lesions, as defined by the American College of Rheumatology (ACR) in 1997, include malar rash, discoid rash, photosensitivity and oral ulcers. It is therefore essential to recognize mucocutaneous lesions to accurately diagnose JSLE. The mucocutaneous lesions can be divided into those with classical histological features (LE specific) and those strongly associated with and forming part of the diagnostic spectrum, but without the classical histological changes of lupus (LE nonspecific). A malar rash is the most commonly associated LE specific dermatological presentation. This skin manifestation is an acute form and also correlates with disease activity. Subacute (polycyclic or papulosquamous lesions) and chronic (discoid lesions) forms, whilst showing classical histological changes supportive of lupus, are less commonly associated with systemic lupus and do not correlate with disease activity. The most commonly associated skin lesions without classical lupus changes are cutaneous vasculitis, oral ulcers and diffuse non-scarring alopecia. These signs frequently relate to disease activity. An understanding of cutaneous signs and symptoms of lupus in children is important to avoid delay in diagnosis. They will often improve as lupus is adequately controlled and their reappearance is often the first indicator of a disease flare. PMID:25587243

  20. Granulomatous Interstitial Nephritis Presenting as Hypercalcemia and Nephrolithiasis

    PubMed Central

    Sharmeen, Saika; Kalkan, Esra; Yi, Chunhui; Smith, Steven D.

    2016-01-01

    We report a case of acute kidney injury as the initial manifestation of sarcoidosis. A 55-year-old male was sent from his primary care physician's office with incidental lab findings significant for hypercalcemia and acute kidney injury with past medical history significant for nephrolithiasis. Initial treatment with intravenous hydration did not improve his condition. The renal biopsy subsequently revealed granulomatous interstitial nephritis (GIN). Treatment with the appropriate dose of glucocorticoids improved both the hypercalcemia and renal function. Our case demonstrates that renal limited GIN due to sarcoidosis, although a rare entity, can cause severe acute kidney injury and progressive renal failure unless promptly diagnosed and treated. PMID:26904327

  1. Idiopathic granulomatous interstitial nephritis responsive to mycophenolate mofetil therapy.

    PubMed

    Leeaphorn, Napat; Stokes, Michael B; Ungprasert, Patompong; Lecates, William

    2014-04-01

    Granulomatous interstitial nephritis (GIN) is a rare histologic disease. Various causes have been reported in the literature, including drugs, sarcoidosis, and infections. Other incidents have no discernible cause and are identified as idiopathic. We report a 68-year-old white man who presented with acute kidney injury and was given a diagnosis of idiopathic GIN. Mycophenolate mofetil treatment was elected because of steroid toxicity. He responded well to mycophenolate mofetil and has been in remission for more than 3 years. To our knowledge, this is the first report of successful treatment with mycophenolate mofetil of an adult patient with idiopathic GIN. PMID:24315767

  2. Levetiracetam-induced severe acute granulomatous interstitial nephritis.

    PubMed

    Chau, Katrina; Yong, Jim; Ismail, Kasim; Griffith, Neil; Liu, Michael; Makris, Angela

    2012-06-01

    Granulomatous interstitial nephritis (GIN) is an uncommon cause of renal failure, which may be caused by drugs. Levetiracetam is an increasingly used anti-epileptic medication that is not known to cause renal toxicity in adults. To our knowledge, levetiracetam has not previously been reported as a cause of GIN. We report the case of a 69-year-old woman who developed haemodialysis-requiring acute renal failure after commencement of treatment with levetiracetam, which was shown to be GIN by renal biopsy. She made a complete recovery with cessation of levetiracetam and treatment with steroids. PMID:26069773

  3. Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus

    PubMed Central

    Knight, Jason S.; Zhao, Wenpu; Luo, Wei; Subramanian, Venkataraman; O’Dell, Alexander A.; Yalavarthi, Srilakshmi; Hodgin, Jeffrey B.; Eitzman, Daniel T.; Thompson, Paul R.; Kaplan, Mariana J.

    2013-01-01

    Recent evidence suggests that enhanced neutrophil extracellular trap (NET) formation activates plasmacytoid dendritic cells and serves as a source of autoantigens in SLE. We propose that aberrant NET formation is also linked to organ damage and to the premature vascular disease characteristic of human SLE. Here, we demonstrate enhanced NET formation in the New Zealand mixed 2328 (NZM) model of murine lupus. NZM mice also developed autoantibodies to NETs as well as the ortholog of human cathelicidin/LL37 (CRAMP), a molecule externalized in the NETs. NZM mice were treated with Cl-amidine, an inhibitor of peptidylarginine deiminases (PAD), to block NET formation and were evaluated for lupus-like disease activity, endothelial function, and prothrombotic phenotype. Cl-amidine treatment inhibited NZM NET formation in vivo and significantly altered circulating autoantibody profiles and complement levels while reducing glomerular IgG deposition. Further, Cl-amidine increased the differentiation capacity of bone marrow endothelial progenitor cells, improved endothelium-dependent vasorelaxation, and markedly delayed time to arterial thrombosis induced by photochemical injury. Overall, these findings suggest that PAD inhibition can modulate phenotypes crucial for lupus pathogenesis and disease activity and may represent an important strategy for mitigating cardiovascular risk in lupus patients. PMID:23722903

  4. Clinical significance of serum properdin levels and properdin deposition in the dermal-epidermal junction in systemic lupus erythematosus.

    PubMed Central

    Schrager, M A; Rothfield, N F

    1976-01-01

    61 biopsies of normal skin from the deltoid area and lesional skin from various sites from 48 patients with systemic lupus erythematosus (SLE) were studied for the presence of properdin, C3, C4, and immunoglobulins (IgG, IgM, and IgA) in the dermal-epidermal junction (DEJ) using direct and indirect immunofluorescence. Properdin was present in 50% of normal and 40% of lesional skins. Properdin was present without C4 in only 2 of 38 nonlesional skin biopsies and in only 2 of 20 lesions. There was no significant difference in incidence of deposition of any of the six proteins studied between nonlesional and lesional skin. The frequency of deposition of each of the proteins correlated with clinical disease activity. The presence of proteins in the DEJ did not correlate with the presence of active renal disease at the time of biopsy nor with previously documented active nephritis. In addition, no other single clinical manifestation correlated with the presence of DEJ deposition of any protein studied. IgA was not demonstrated in the DEJ of nonlesional skin of 16 patients in remission and was present in 7 of 23 patients with active disease (P less than 0.05). Deposition of properdin in lesional skin correlated with the presence of extracutaneous disease activity (P less than 0.05). Analysis of serologic studies on serum obtained at the time of biopsy revealed a statistically significant correlation between C4 and C3 (r = 0.67). This correlation was stronger than that between properdin and C4 (r = 0.37). Titer of antinuclear antibody and percent of DNA binding correlated better with C4 levels than with properdin levels. Serum properdin levels were significantly lower in patients with active disease than in those in remission (P less than 0.05). Serum properdin levels were significantly lower in patients with properdin deposits in lesional skin than in those without properdin deposits. The data suggest that both alternative and classical pathways are activated in patients

  5. When Coke Is Not Hydrating: Cocaine-Induced Acute Interstitial Nephritis.

    PubMed

    Bahaa Aldeen, Mohammed; Talibmamury, Nibras; Alalusi, Sumer; Nadham, Omar; Omer, Abdel Rahman; Smalligan, Roger D

    2014-01-01

    home with an improving Cr of 3.5 mg/dL, back to baseline of 1.5 in 8 weeks. Discussion. Internists encounter patients with acute kidney injury (AKI) on a daily basis, most of which can be explained by prerenal azotemia, acute tubular necrosis (ATN), obstruction, or rhabdomyolysis among other etiologies. Cocaine is only rarely implicated as an etiology of AKI and if it is, usually the injury is due to ATN or pigment effects. Acute interstitial nephritis (AIN) caused by cocaine, on the other hand, has only been described in a handful of cases. AIN is a renal lesion that causes a decline in creatinine clearance and is characterized by an inflammatory infiltrate in the kidney interstitium and is most often associated with drug therapy. AIN can also be seen in autoimmune disorders like systemic lupus erythematosus, Sjögren's syndrome, or sarcoidosis; or with infections remote to the kidney like Legionella, leptospirosis, and streptococcal disease. Our case was very similar to the other reported cases of AIN due to cocaine in that all have occurred in middle-aged African American males and all have responded to steroids. This case reminds clinicians to consider AIN in patients with AKI and a history of cocaine abuse. PMID:26425622

  6. Systemic lupus erythematosus.

    PubMed

    Kaul, Arvind; Gordon, Caroline; Crow, Mary K; Touma, Zahi; Urowitz, Murray B; van Vollenhoven, Ronald; Ruiz-Irastorza, Guillermo; Hughes, Graham

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future. PMID:27306639

  7. Overview of neonatal lupus.

    PubMed

    Johnson, Benay

    2014-01-01

    Neonatal lupus (NL) is defined by the presentation of the fetus and the newborn who possess autoantibodies received from the mother. It is the dysfunction of the maternal immune system that leads to the production of autoantibodies to anti-Sjögren syndrome-A, anti-Sjögren syndrome-B, and anti-ribonuclear protein antigens. These antibodies are shared through the placenta and produce bodily changes in the fetal skin and heart, as well as potential changes in other body systems. Congenital complete heart block is the most dangerous manifestation of NL that can occur in utero or after birth. This article will provide an overview the presentation of NL and current therapies. Prenatal steroids have been the mainstay of therapy to try to reverse first- and second-degree congenital heart block and to prevent progression to a more advanced stage. New therapies are combining steroids with intravenous immunoglobulin and plasmapheresis. This article will provide guidelines for practitioners so they can consider NL as a differential diagnosis when presented with cutaneous lesions, congenital heart block, or abnormal findings in the hematologic, hepatobiliary, neurologic, and musculoskeletal systems. PMID:24100008

  8. Creatinine - blood

    MedlinePlus

    ... Hepatorenal syndrome Interstitial nephritis Lupus nephritis Malignant hypertension Medullary cystic kidney disease Membranoproliferative glomerulonephritis Muscular dystrophy Polymyositis - adult Preeclampsia Prerenal ...

  9. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks.

    PubMed

    Rekvig, O P

    2015-01-01

    Antibodies to mammalian dsDNA have, for decades, been linked to systemic lupus erythematosus (SLE) and particularly to its most serious complication, lupus nephritis. This canonical view derives from studies on its strong association with disease. The dogma was particularly settled when the antibody was included in the classification criteria for SLE that developed during the 1970s, most prominently in the 1982 American College of Rheumatology (ACR), and recently in The Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. There are several problems to be discussed before the anti-dsDNA antibody can be accepted without further distinction as a criterion to classify SLE. Old and contemporary knowledge make it clear that an anti-dsDNA antibody is not a unifying term. It embraces antibodies with a wide spectrum of fine molecular specificities, antibodies that are produced transiently in context of infections and persistently in the context of true autoimmunity, and also includes anti-dsDNA antibodies that have the potential to bind chromatin (accessible DNA structures) and not (specificity for DNA structures that are embedded in chromatin and therefore unaccessible for the antibodies). This critical review summarizes this knowledge and questions whether or not an anti-dsDNA antibody, as simply that, can be used to classify SLE. PMID:24533624

  10. Renal Transplantation in Systemic Lupus Erythematosus: Outcome and Prognostic Factors in 50 Cases from a Single Centre

    PubMed Central

    Cairoli, Ernesto; Sanchez-Marcos, Carolina; Espinosa, Gerard; Glucksmann, Constanza; Ercilla, Guadalupe; Oppenheimer, Federico; Cervera, Ricard

    2014-01-01

    Background. End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Objectives. To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Results. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36 ± 10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n = 12), acute rejection (n = 2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P = 0.007) and positive anti-HCV antibodies (P = 0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Conclusion. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure. PMID:25013800

  11. [A rare case of an acute abdomen patient with gangrene of the colon as a complication of systemic lupus erythematosus].

    PubMed

    Dolák, S; Prochotský, A; Mifkovič, A; Škultéty, J; Ježovít, M; Koudelka, P; Bluska, P

    2015-02-01

    The authors present a case report of a 39-year-old woman with acute abdomen - a comorbid patient with systemic lupus erythematosus, chronic renal insufficiency as a complication of lupus nephritis, included in a haemodialysis programme. The patient had also undergone transplantation of the left kidney in the past. She was initially admitted to the Department of Traumatology for a total endoprosthesis procedure due to bionecrosis of the head of the thigh bone. Postoperatively, the patients condition was complicated by gangrene of the colon confirmed by CT scan and during the operation. The patient was operated on - subtotal colectomy, terminal ileostomy and left-sided ovariectomy was performed. The postoperative course was complicated by perforation of the jejunum which was sutured. The patient was admitted to ICU and, after recovery, to our surgical department. Because of the metabolic disturbance she was treated in the internal medicine department. After 60 days she was discharged in a good condition, walking and with full per os realimentation.Key words: lupus erythematosus gangrene of the colon acute abdomen. PMID:25659257

  12. Anti-Proliferative Actions of T-Type Calcium Channel Inhibition in Thy1 Nephritis

    PubMed Central

    Cove-Smith, Andrea; Mulgrew, Christopher J.; Rudyk, Olena; Dutt, Neelanjana; McLatchie, Linda M.; Shattock, Michael J.; Hendry, Bruce M.

    2014-01-01

    Aberrant proliferation of mesangial cells (MCs) is a key finding in progressive glomerular disease. TH1177 is a small molecule that has been shown to inhibit low-voltage activated T-type Ca2+ channels (TCCs). The current study investigates the effect of TH1177 on MC proliferation in vitro and in vivo. The effect of Ca2+ channel inhibition on primary rat MC proliferation in vitro was studied using the microculture tetrazolium assay and by measuring bromodeoxyuridine incorporation. In vivo, rats with Thy1 nephritis were treated with TH1177 or vehicle. Glomerular injury and average glomerular cell number were determined in a blinded fashion. Immunostaining for Ki-67 and phosphorylated ERK were also performed. The expression of TCC isoforms in healthy and diseased tissue was investigated using quantitative real-time PCR. TCC blockade caused a significant reduction in rat MC proliferation in vitro, whereas L-type inhibition had no effect. Treatment of Thy1 nephritis with TH1177 significantly reduced glomerular injury (P < 0.005) and caused a 49% reduction in glomerular cell number (P < 0.005) compared to the placebo. TH1177 also reduced Ki-67-positive and pERK-positive cells per glomerulus by 52% (P < 0.01 and P < 0.005, respectively). These results demonstrate that TH1177 inhibits MC proliferation in vitro and in vivo, supporting the hypothesis that TCC inhibition may be a useful strategy for studying and modifying MC proliferative responses to injury. PMID:23746655

  13. Expression of major histocompatibility complex class II antigens in porcine leptospiral nephritis.

    PubMed

    Radaelli, E; Del Piero, F; Aresu, L; Sciarrone, F; Vicari, N; Mattiello, S; Tagliabue, S; Fabbi, M; Scanziani, E

    2009-09-01

    Class II major histocompatibility complex (MHCII) is required for the presentation of antigens to CD4 helper T cells. During nephritis, not only primary antigen presenting cells such as histiocytes and lymphocytes, but also cytokine-stimulated tubular epithelial cells express MHCII. Leptospirosis in fattening pigs is characterized by several degrees of nephritis, from absence of lesions to severe multifocal tubulo-interstitial inflammation. Renal tissue from 20 8-month-old pigs with spontaneous nephritis and 6 control pigs without renal lesions were investigated for leptospirosis by indirect immunohistochemistry (IHC) and polymerase chain reaction (PCR). IHC for MHCII also was performed on renal samples. Serum samples were tested for different serovars of Leptospira interrogans. Control pigs were free of interstitial nephritis and negative for leptospirosis by all tests. In pigs with nephritis, serology was positive for serovar Pomona in 19/20 pigs. In 16 of these 19 pigs, leptospiral renal infection was confirmed by PCR and/or indirect IHC. Nephritic lesions were classified histologically into perivascular lymphocytic (4 pigs), lymphofollicular (6 pigs), lymphohistiocytic (8 pigs), and neutrophilic (2 pigs) pattern. MHCII expression by histiocytes and lymphocytes was observed in all lesions. Prominent MHCII expression in regenerating tubular epithelium was observed in lymphofollicular and lymphohistiocytic nephritis. No tubular colocalization between leptospiral and MHCII antigen was observed. Results suggest that during leptospiral nephritis, MHCII contributes to the intensity of the inflammatory response. Furthermore de novo MHCII expression in regenerating tubules may play a role in the defence mechanism against leptospiral tubular colonization. PMID:19179617

  14. Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice.

    PubMed

    Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T; Lucas, Julie A; Rabacal, Whitney A; Croker, Byron P; Zong, Xiao-Hua; Stanley, E Richard; Kelley, Vicki R

    2008-11-15

    Sunlight (UVB) triggers cutaneous lupus erythematosus (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø)-mediated mechanism in MRL-Fas(lpr) mice. By constructing mutant MRL-Fas(lpr) strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex vivo gene transfer to deliver CSF-1 intradermally, we determined that CSF-1 induces CLE in lupus-susceptible MRL-Fas(lpr) mice, but not in lupus-resistant BALB/c mice. UVB incites an increase in Møs, apoptosis in the skin, and CLE in MRL-Fas(lpr), but not in CSF-1-deficient MRL-Fas(lpr) mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Møs that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Fas(lpr) but not lupus-resistant BALB/c mice. Taken together, CSF-1 is envisioned as the match and lupus susceptibility as the tinder leading to CLE. PMID:18981160

  15. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    PubMed Central

    Li, Xiangling; Wang, Yanqiang

    2016-01-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  16. Cyclic AMP-Responsive Element Modulator α Polymorphisms Are Potential Genetic Risks for Systemic Lupus Erythematosus

    PubMed Central

    Guo, Qian; Chen, Xuyong; Du, Yan; Guo, Jianping; Su, Yin