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Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease of unknown etiology, whose hallmark is the production of autoantibodies. B cells are promising targets for novel SLE therapies. In 2011, belimumab (Benlysta®), a fully humanized monoclonal antibody inhibiting B-cell activation and proliferation, was the first medication in 50 years to be approved by the US Food and Drug Administration to treat adult SLE. This review discusses the current experience with B-cell-targeted therapies, including those targeting B-cell-surface antigens (rituximab, ocrelizumab, ofatumumab, obinutuzumab, obexelimab, epratuzumab, daratumumab), B-cell survival factors (belimumab, tabalumab, atacicept, blisibimod), or B-cell intracellular functions (ibrutinib, fenebrutinib, proteasome inhibitors), for the management of SLE. It focuses on ongoing clinical trials and real-world post-marketing use, where available, including their safety profiles, and concludes with our recommendations for B-cell-centric approaches to the management of SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement. Patients with SLE feature a lower tendency to develop erosive arthritis in comparison with rheumatoid arthritis (RA); however, in some arthritis cases it may be difficult to differentiate SLE from RA. Anti-cyclic citrullinated peptide (Anti-CCP) antibodies are highly-specific for RA. The current study evaluated the relationship between anti-CCP and arthritis in SLE patients. In this study, anti-CCP antibodies were tested in 300 patients with SLE. The INOVA Diagnostics QUANTA Lite™ CCP IgG ELISA and the Axis-Shield Diagnostics Diastat™ anti-CCP ELISA test were applied. Patients were divided into two groups: those with and those without arthritis. Patients with chronic arthritis (>6 weeks) had radiography done on the involved joints. Chi square and Fisher’s exact tests were applied to compare the two subsets. Anti-CCP antibodies were detected in 4.7% of all patients (CI: 2.6-7.8). Anti-CCP was positive in 6.4% of patients with arthritis and 2.3% of patients without arthritis (P=0.09). From seven patients with chronic arthritis, one had both positive anti-CCP and erosions. In the studied Iranian SLE patients, anti-CCP levels were higher in patients with arthritis than in those without arthritis. This study did not show any association of anti-CCP with erosion in SLE patients with arthritis. Ethnic and geographical variance may have influenced the results. More studies on chronic arthritis in SLE are needed to confirm this hypothesis.

Made available in DSpace on 2018-12-11T17:11:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-04-01 Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies (p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation. Pediatric Rheumatology Unit Children's Institute Faculdade de Medicina da Universidade de São Paulo (FMUSP) Division of Rheumatology Faculdade de Medicina da Universidade de São Paulo (FMUSP) Pediatric Rheumatology Unit State University of Campinas (UNICAMP) Pediatric Rheumatology Unit Universidade Federal de São Paulo (UNIFESP) Pediatric Rheumatology Division São Paulo State University (UNESP) Faculdade de Medicina de Botucatu Pediatric Rheumatology Unit Hospital Darcy Vargas Pediatric Rheumatology Unit Ribeirão Preto Medical School FMUSP Pediatric Rheumatology Division São Paulo State University (UNESP) Faculdade de Medicina de Botucatu

B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF. Furthermore, blisibimod has a unique structure built on four high-affinity BAFF-binding peptides fused to the IgG1-Fc carrier. It was tested in phase I and II trials in SLE where it showed safety and tolerability. While it failed to reach the primary endpoint in a recent phase II trial, post hoc analysis demonstrated its efficacy in SLE patients with higher disease activity. Based on these results, blisibimod is currently undergoing phase III trials targeting this responder subpopulation of SLE patients. The advantage of blisibimod, compared to its competitors, lies in its higher avidity for BAFF, but a possible drawback may come from its immunogenic potential and the anticipated loss of efficacy over time.

Objective: Previous studies have shown that biologic agents out of the nine medicines might be beneficial for the treatment of SLE. The aim of this study was to evaluate the most effective medication of six biologic agents in treatment of SLE using network meta-analysis (NMA). The performance of these processes is ranked according to the results of this analysis. Methods: Multiple databases including PubMed, EMBASE and Cochrane Library was used to identify applicable articles and collect relevant data to analyzed by using STATA (13.0) software. The papers included in this study were divided into control group (placebo) and observation group (one of the six medicines). Results: A total of 21 eligible RCTs of biologic agents were identified, a total of 995 papers were included, and the results showed that the belimumab had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking (SUCRA) curve of 75.0, was significantly superior (P < 0.05) to placebo alone. The blisibimod was the worst, with a SUCRA value of 29.4. The other biologic agents (atacicept, blisibimod, epratuzumab, rituximab, tabalumab) were insignificantly superior (P > 0.05) to placebo alone. Conclusions: Belimumab had the highest probability of being the best treatment for SLE compared with the other biologic agents (atacicept, blisibimod, epratuzumab, rituximab, tabalumab). The other biologic agents indicated an insignificant difference in efficacy for the treatment of SLE compared with placebo. doi: https://doi.org/10.12669/pjms.35.6.771 How to cite this:Tao MJ, Cheng P, Jin LR, Zhou J, Shi W, Peng H, et al. The safety and efficacy of biologic agents in treatment of systemic lupus erythematosus: A network meta-analysis. Pak J Med Sci. 2019;35(6):1680-1686. doi: https://doi.org/10.12669/pjms.35.6.771 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

BACKGROUND:Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4. OBJECTIVES:To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity. METHODS:442 patients with SLE with antinuclear antibodies or anti-dsDNA and Safety of Estrogen in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥10 on standard-of-care medications were randomised to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from week 8. The primary end point was the week 52 SLE Responder Index-6 (SRI-6). RESULTS:The SRI-6 primary end point was not met. There was a statistically significant steroid-sparing effect, and significantly more blisibimod-treated subjects achieved corticosteroid taper. Increased blisibimod treatment effect on SRI-6 was observed in subjects who achieved a concomitant decrease in corticosteroid dose from baseline. In subjects with baseline urinary protein:creatinine ratio (UPCR) ≥56.5 mg/mmol, significantly higher proportions of blisibimod subjects achieved >50% reduction in UPCR and/or UPCR

The current therapeutic approach to the difficult manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) remains empirical and is based on clinical experience. Available data on the use of rituximab in refractory NPSLE come from a large number of case reports and some open-label studies. Two patients with persistently active NPSLE, despite conventional therapy, responded dramatically to rituximab are described in this chapter. Current evidence on the therapeutic use of rituximab in this chapter is also analyzed through the English-language literatures. Evidence for the effectiveness of rituximab as induction therapy in NPSLE is based solely on several case reports and non-controlled trials. Although it is not yet possible to make definite recommendations, the global analysis of these cases supports the off-label use of rituximab in cases of severe refractory NPSLE. Furthermore, we present the blockade of new targets which may impact the future treatment of NPSLE.

Methods Levels of serum BAFF, IgG anti-BAFF and BAFF-IgG complexes were quantified by enzyme-linked immunosorbent assay. IgG anti-BAFF and BAFF-IgG complexes were further characterized using serum fractions obtained by fast protein liquid chromatography. To study the association of serum BAFF, IgG anti-BAFF and BAFF-IgG complex levels with SLE manifestations, 373 visits from 178 patients prospectively included in the Swiss SLE Cohort Study were analysed. Results While IgG anti-BAFF levels were not associated with clinical manifestations of SLE, serum BAFF levels correlated with disease activity and were higher in patients with renal involvement. Interestingly, we could also demonstrate the occurrence of BAFF-IgG complexes of different sizes in the sera of SLE patients, which were not due to treatment with belimumab and differed from complexes constructed in vitro. Most strikingly, the levels of these BAFF-IgG complexes were found to strongly correlate with overall disease activity, low complement levels and a history of lupus nephritis. Conclusion BAFF-IgG complexes strongly correlate with disease activity in SLE patients, suggesting a pathogenic role in SLE.

Background In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE). Methods C4d levels were determined by enzyme-linked immunosorbent assay in plasma samples of patients with established SLE using a novel approach based on detection of a short linear cleavage neoepitope. Cross-sectional associations were studied in 98 patients with SLE with samples taken at lower or higher respective disease activity. Temporal associations were investigated in 69 patients with SLE who were followed longitudinally for up to 5 years. Plasma samples from 77 healthy donors were included as controls. Results C4d levels were negligible in healthy control subjects and significantly increased in patients with SLE in the cross-sectional study (p < 0.0001). C4d levels discriminated between higher and lower disease activity according to ROC curve analysis (p < 0.001), exhibiting a positive predictive value of 68%. At higher disease activity, C4d levels correlated with the modified Systemic Lupus Erythematosus Disease Activity Index (p = 0.011) and predominantly with lupus nephritis (p = 0.003), exhibiting a sensitivity of 79% to identify patients with nephritis. High C4d levels together with the presence of anti-dsDNA autoantibodies preceded and thus predicted future lupus nephritis in the longitudinal study (OR 5.4, 95% CI 1.4–21.3). When we considered only patients with renal involvement (19 of 69) during the longitudinal study, we found that high C4d levels alone could forecast recurrence of future lupus nephritis (OR 3.3, 95% CI 1.2–9.6). Conclusions C4d appears to be a valuable marker for use in monitoring of patients with SLE, particularly for lupus nephritis. Importantly, C4d levels can predict impending flares of lupus nephritis and may thus be useful for informing treatment.

Autoimmune rheumatic disorders have complex etiopathogenetic mechanisms in which B cells play a central role. The importance of factors stimulating B cells, notably the B-cell activating factor (BAFF) and A proliferation inducing ligand (APRIL) axis is now recognized. BAFF and APRIL are cytokines essential for B-cell proliferation and survival from the immature stages to the development of plasma cells. Their levels are increased in some subsets of patients with autoimmune disorders. Several recent biologic drugs have been developed to block this axis, namely belimumab [already licensed for systemic lupus erythematosus (SLE) treatment], tabalumab, atacicept and blisibimod. Many clinical trials to evaluate the safety and efficacy of these drugs in several autoimmune disorders are ongoing, or have been completed recently. This review updates the information on the use of biologic agents blocking BAFF/APRIL for patients with SLE, rheumatoid arthritis, Sjögren’s syndrome and myositis.

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease of multifactorial pathoaetiology. One of the most serious manifestations is lupus nephritis. The pathogenesis of SLE has not been well elucidated, but it has been reported that interleukin-17 (IL-17) and Th17 cells play important roles in the pathogenesis of SLE. IL-17A, a member of IL-17 family, amplifies the immune response by inducing the local production of chemokines and cytokines, recruiting neutrophils and monocytes, augmenting the production of autoantibodies, and aggravating the inflammation and damage of target organs such as the kidney in SLE. In recent years, several IL-17A pathway inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibody and the anti-17RA monoclonal antibody. Several agents have shown great success in Phase II trials in multiple autoimmune diseases such as psoriasis, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and non-infectious uveitis, which has sparked the urgent need of anti-IL-17A as innovative therapeutic option in controlling disease activity of moderate-to-severe SLE. Here, we review and summarize current progress in IL-17A and SLE from in vitro studies, human expression studies, and animal models, providing novel insight into its therapeutic potential.

Key advances in lupus research in 2015 highlight the contribution of T cells to the pathogenesis of the disease. The findings not only shed light on the regulation and activity of these cells, but also suggest several novel therapeutic targets.

Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index. We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23). Subgroup analysis was carried out on the basis of organ damage (with/without, 42/33) and biopsy-proven LN (with/without, 27/48; active LN, n = 13; inactive LN, n = 14). Of thirty deregulated proteins between SLE and the healthy controls (P corr

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by excess B- and T-cell activation, the development of autoantibodies against self-antigens including nuclear antigens, and immune complex deposition in target organs, which triggers an inflammatory response and tissue damage. The genetic and environmental factors that contribute to the development of SLE have been studied extensively in both humans and mouse models of the disease. One of the important genetic contributions to SLE development is an alteration in the expression of the transcription factor Ets1, which regulates the functional differentiation of lymphocytes. Here, we review the genetic, biochemical, and immunological studies that have linked low levels of Ets1 to aberrant lymphocyte differentiation and to the pathogenesis of SLE.

Background: The clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated. Objectives: This study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients. Methods: A hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test. Results: Forty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%). Study limitations: The sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias. Conclusions: The level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Background Anti-Ro antibodies (Ab) are especially directed against two antigens, Ro52 and Ro60, with different structure and function. Studies in systemic lupus erythematosus (SLE) have been described a relationship between the presence of anti-Ro Ab and dry syndrome, subacute cutaneous lupus, myocardial involvement or minor renal involvement. However, studies about the clinical usefulness of determining the 2 specificities of anti-Ro Ab in SLE are not conclusive. It seems that anti-Ro52 could be associated with joint involvement and lung disease, while anti-Ro60 could be related to late-onset SLE. In this paper we evaluate the clinical usefullness of anti-Ro52 and Ro60 Ab chemiluminescence quantification in patients with SLE. Objectives To analyze the presence of anti-Ro52 and Ro60 Ab in a cohort of patients with SLE and evaluate its correlation with clinical, analytical and immunological parameters. Methods 152 patients with SLE (according to the SLICC criteria 2013) attended in an university hospital were included. Qualitative immunoblot analysis of anti-Ro Ab was performed on all of them; those with positive values were also assessed by a chemiluminescence quantification of anti-Ro52 and Ro60 Ac (normality Results 91% (138) were women with a mean age of 46±12 years (range, 20–75) and an average SLE evolution of 12±7 years (range, 1–40). 32% (49/138) of the patients had anti-Ro positive determination by immunoblot: 36 were anti-Ro52 positive (mean value 696±726 CU) and 48 anti-Ro60 positive (mean value 504±696 CU) by chemiluminescence. Only one anti-Ro52 positive patient was anti-Ro60 negative. 10.5% had late-onset SLE. The mean SLEDAI was 1.84±2.48 while the SLICC was 0.32±0.7, with a mean anti(ds)DNA Ac values about 207.87±357.15 IU/ml. 37.5% had hypocomplementemia. Anti-Ro positive patients by immunoblot had a higher value of anti(ds)DNA compared to the patients without Ro positive values and patients with both positivity by chemiluminescence had lower prevalence of APS, however the quantitative values of anti-Ro52 and anti-Ro60 were not related with clinical, analytical or immunological parameters. Conclusions 32% of patients in the cohort were anti-Ro positive being mostly anti-Ro60 positive. The presence of anti-Ro Ab was associated with higher value of antiDNAds and lower prevalence of APS. However, the quantitative values of anti-Ro52 and anti-Ro60 Ab by chemiluminescence were not related to the different parameters analyzed in the study. These results indicate the need to assess the quantification of anti-Ro Ab in a larger cohort of patients with SLE. Disclosure of Interest None declared

Background Targeted, biologic inhibitors of B-cell Activating Factor (BAFF) have been evaluated in Phase 3 trials in over 5000 patients with SLE. Post hoc analyses of these studies identify lower placebo response and greater treatment effect using more stringent endpoints in patients entering with higher disease activity, greater corticosteroid doses, and/or anti-double-stranded DNA (dsDNA) and low complement C3 or C41,2. Objectives The Phase 3 CHABLIS-SC1 trial evaluated blisibimod, an inhibitor of B-cell activating factor (BAFF), in a “responder population” identified from prior studies with this drug class. Methods 442 SLE patients with anti-nuclear antibodies or anti-dsDNA, SELENA-SLEDAI score ≥10 on standard of care medications were randomized to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from Week 8 with the goal to reach ≤7.5 mg prednisone/day. The primary endpoint at Week 52 was the SLE Responder Index-6 (SRI-6): ≥6-point improvement in SELENA-SLEDAI, no new BILAG 1A or 2B domain scores, and Results This study did not meet its primary endpoint at Week 52. Response rates to blisibimod were equivalent to past trials of BAFF inhibitors, but the placebo response was greater. A slightly higher proportion of subjects on blisibimod met the SRI-6 and SRI-4 criteria at most timepoints and more blisibimod-treated subjects achieved corticosteroid taper to prednisone ≤7.5 mg/day from Week 40 through Week 52 (p=0.04 at Week 44). Reductions in peripheral B cell lineages, anti-dsDNA, anti-phospholipid antibodies, and serum immunoglobulins, and increases in complement C3 and C4 were observed with blisibimod (see Table). Blisibimod was well-tolerated. The most common adverse events were upper respiratory tract infection (10.6% vs 14.3% on placebo), urinary tract infection (6.9% vs 10.7%), injection site erythema (7.8% vs 2.0%), injection site reaction (7.3% vs 2.6%), and diarrhea (7.3% vs 2.6%). Conclusions With a deliberate focus on a “responder population” for whom lower placebo rates were observed in previous trials, much higher placebo response rates were observed in the CHABLIS-SC1 trial. Modest benefits of blisibimod were observed on serological effects and corticosteroid tapering. References van Vollenhoven RF et al. Ann Rheum Dis. 2012;71:1343. Merrill JT et al. Ann Rheum Dis. 2016;75(2):332–40. Disclosure of Interest J. Merrill Grant/research support from: BMS, GSK, Consultant for: Anthera, GSK, EMD Serono, Lilly, Astra Zeneca, BMS, UCB, Celgene, Biogen, R. Martin Shareholder of: Anthera, Employee of: Anthera, W. Shanahan Shareholder of: Anthera, Employee of: Anthera, M. Scheinberg Consultant for: GSK,Pfizer, Janssen, Genzyme,Anthera, Novartis, Speakers bureau: GSK,Pfizer, Janssen, Genzyme,Anthera, Novartis, K. Kalunian Grant/research support from: GSK, Celgene, UCB, Consultant for: Anthera, Genentech, BMS, Lilly, Biogen, Shire, Exagen, D. Wofsy Consultant for: Anthera, Genentech, Amgen, GSK

The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves' disease (GD) among Mexican patients.We conducted a case-control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals. PTPN22 genotypes were determined using the TaqMan 5' allele discrimination assay.PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004), but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated that this polymorphism is associated with RA susceptibility (OR 4.17, p = 0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR 0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD.Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.

Autoimmune diseases often share common susceptibility genes. Most genetic variants associated with susceptibility to systemic lupus erythematosus are also associated with other autoimmune diseases. The X-linked variant rs2294020 is positioned in exon 7 of the CCDC22 gene. The encoded protein functions in the regulation of NF-kB, a master regulator in immune response. The aim of this study is to investigate whether the rs2294020 polymorphism may be a general susceptibility factor for autoimmunity. We evaluated case-control association between the occurrence of rs2294020 and different autoimmune diseases, including new data for systemic lupus erythematosus and previous genome-wide association studies (GWAS) (though most did not analyse the X chromosome) of psoriasis, celiac disease, Crohn’s disease, ulcerative colitis, multiple sclerosis, vitiligo, type-1 diabetes, rheumatoid arthritis, and ankylosing spondylitis. Cases from patients affected by amyotrophic lateral sclerosis and type-2 diabetes were also included in the study. We detected nominal significant associations of rs2294020 with systemic lupus erythematosus (additive model test: p=0.01), vitiligo (p =0.016), psoriasis (p =0.038), and in only one of two studies of multiple sclerosis (p =0.03). Our results suggest that rs2294020 is associated with the risk of several autoimmune diseases in European populations, specifically with diseases that present themselves, among else, in the skin.

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

To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial.547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI).Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo.This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3.NCT01162681.

In the last 50 years, only one drug has achieved marketing approval for treatment of systemic lupus erythematosus (SLE) by global regulatory authorities. This drug, belimumab, is a monoclonal antibody that binds to and inhibits BAFF. Blisibimod is a ‘peptibody’ consisting of four BAFF-binding domains fused to the Fc domain of human IgG1, and is structurally distinct from the anti-BAFF monoclonal antibodies such as belimumab and tabalumab. Compared with tabalumab and belimumab, blisibimod's binding affinity for BAFF (1 pM) is 126–250-fold higher, while its serum half-life (8–10 days) is approximately half as long. Completed Phase I and Phase II clinical trials with blisibimod provide the first evidence that subcutaneous administration of a biologic therapeutic may lead to improvements in SLE disease activity, as well as disease-associated pharmacodynamic markers, including peripheral B cells, autoantibodies and decreased complement consumption. Furthermore, the effect to significantly decrease the urinary ...

Despite significant advances in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), there are only a few drugs approved by the regulatory agencies across the world for the treatment of these patients; in fact, many of the compounds subjected to clinical trials have failed in achieving their primary endpoints. Current therapeutic options include antimalarials which should be used in all SLE patients unless they are strongly contraindicated, glucocorticoids which should be used at the lowest possible dose and for the shortest possible time, and immunosuppressive drugs which should be used judiciously, mainly in patients with severe organ involvements or receiving high doses of steroids to control their disease. Despite improvement on the survival of SLE patients, damage accrual has not varied over the last few decades, reflecting a gap between these therapeutic options and the expectations of these patients and their treating physicians. Biologic compounds can be used in some refractory cases. However, their cost is of great concern for both the patients and the health system. Cost is of special importance in low-income countries, because low-income SLE patients tend to experience a more severe disease having an overall worse prognosis which is compounded by their limited access to the health system. Although a treatment to target based on defined molecular pathways for specific disease subsets is appealing, this is not yet a reality. This review addressed current therapeutic options for SLE patients and the state of the art of investigational drugs targeting pathogenic pathways identified in these patients.

Drug-induced lupus erythematosus is defined as a syndrome with clinical and serological features similar to systemic lupus erythematosus that is temporally related to continuous drug exposure and which resolves after discontinuation of this drug. More than 90 drugs, including biological modulators such as tumour necrosis factor-α inhibitors and interferons, have been identified as likely ‘culprits’. While there are no standard diagnostic criteria for drug-induced lupus erythematosus, guidelines that can help to distinguish drug-induced lupus erythematosus from systemic lupus erythematosus have been proposed and several different patterns of drug-induced lupus erythematosus are emerging. Distinguishing drug-induced lupus erythematosus from systemic lupus erythematosus is important because the prognosis of drug-induced lupus erythematosus is usually good when the drug is withdrawn. This review discusses the differences between drug-induced lupus erythematosus and systemic lupus erythematosus, the mechanisms of action of drug-induced lupus erythematosus and drugs that are usually associated with drug-induced lupus erythematosus, with particular focus on the biological treatments.

In ARD , a group of outstanding investigators report the results of another lupus trial missing its primary endpoint, namely the Phase III CHABLIS-SC study aimed at testing the efficacy of blisibimod,1 composed of a tetrameric BAFF/BLyS domain fused to a human IgG1 Fc region. Interestingly, blisibimod displayed unequivocal effects on biomarkers, such as reduction of circulating B cells, serum immunoglobulin titres or anti-DNA antibodies and increase in complement levels, changes in line with its mode of action and known to correlate with improved clinical outcome. Moreover, although the trial was not intended to demonstrate renal efficacy, an interesting reduction of proteinuria was noticed. This paradox raises the possibility that the failure of CHABLIS-SC stems more from the choice of the primary efficacy endpoint than from the drug itself, the more so as BAFF/BLyS was proven to be an appropriate target in four previous clinical trials, namely the belimumab BLISS-52,2 BLISS-763 and BLISS-SC4 and the tabalumab ILLUMINATE-25 studies, all showing the same effects on biomarkers and a significant, although modest, clinical efficacy. Of note, while the primary outcome (SRI-6) failed in the CHABLIS-SC trial, a trend (p=0.056) in favour of blisibimod was demonstrated when a modified endpoint was used, which takes into account, besides SRI-6, achievement of a steroid dose reduction between weeks 40 and 52 compared with day 1. The main goal of this editorial is to propose a ‘U loop’ in …

T-helper (Th) cells abnormalities are considered to be associated with the pathogenesis of Systemic lupus erythematosus (SLE). Recently, The Th22 cells have been identified and implicated in the pathogenesis of autoimmune diseases such as Rheumatoid arthritis (RA), although therir role in Systemic lupus erythematosus (SLE) remains unclear. The present study intends to investigate their roles in SLE.Clinical data were collected in 65 SLE patients and 30 healthy controls. The patients were divided into active and inactive groups. CD4(+)IFN-γ(-)IL-17(-)IL-22(+)Tcells (Th22 cells),CD4(+) IFN-γ(-)IL-22(-)IL-17(+)T cells (Th17 cells),and CD4(+) IFN-γ(+) (Th1 cells) were assayed by flow cytometry. Serum interleukin-22 (IL-22) and IL-17 levels were measured by enzyme-linked immunosorbent assay.The main observation focused on increased Th22 cells in patients with sole lupus skin disease and decreased Th22 cells in patients with sole lupus nephritis. Likewise, concentrations of serum IL-22 were increased in patients with sole lupus skin disease, and decreased in patients with sole lupus nephritis. Additionally, there was a positive correlation between the percentage of Th22 cells and IL-22 production. The percentage of Th17 cells or concentration of serum IL-17 correlated positively with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).Th22 seems to be a more significant index to predict the tissue involvement of SLE than Th17, although Th17 may play a role in the activity of SLE.

Aim of the workTo further investigate the possible role of IL-18 in the pathogenesis of systemic lupus erythematosus (SLE) and development of lupus nephritis (LN), and to explore its relationship with pathological classes of LN, degree of acute renal activity and chronic damage.Patients and methodsForty-one SLE patients with LN, thirty-one lupus non-nephritis patients and fifteen age and sex matched healthy controls were enrolled in this study. SLE patients were subjected to disease activity assessment by SLEDAI, renal disease activity assessment by the Systemic Lupus International Collaborating Clinics (SLICC) Renal Activity Score, laboratory investigations including measurement of serum interleukin-18 using Enzyme Linked Immunosorbent Assay. Renal biopsy was obtained from LN patients and pathological classification was made according to World Health Organization (WHO) criteria. Analysis of activity and chronicity indices was done on these biopsy specimens.ResultsSerum levels of IL-18 were significantly higher in patients with LN than lupus non-nephritis patients and healthy controls (p

Epidemiological data suggest that the Epstein-Barr virus (EBV) is associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. However, it is not clear whether EBV plays a role in the pathogenesis of these diseases, and if so, by which mechanisms the virus may contribute. In this review, we discuss possible viral and immunological mechanisms that might explain associations between EBV and autoimmune diseases and whether these associations represent causes or effects of inflammation and autoimmunity.

Purpose The role of biologic disease-modifying drugs in patients with systemic lupus erythematosus (SLE) remains controversial. Methods Following systematic review and meta-analysis protocol, we searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov in January 2017 to identify all studies of people with SLE treated with biologic response modifiers. We performed direct frequentist random effects meta-analyses, calculated pooled relative risk and number needed to treat to achieve an outcome in 1 patient (NNT) as reciprocal to statistically significant absolute risk difference, and graded the quality of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Findings Seven meta-analyses, 33 publications of randomized controlled trials (RCTs), and 5 observational studies met inclusion criteria. All studies enrolled previously treated adults with moderate to severe SLE despite conventional immunosuppression. In patients with extrarenal SLE, adjunctive belimumab (10 mg/kg) increases the rates of clinical response (moderate quality evidence from 2 RCTs, 1125 patients, NNT = 8 [95% CI, 6–16]), whereas adjunctive rituximab or abatacept are ineffective. In adults with lupus nephritis, adjunctive rituximab (4000 mg, very-low-quality evidence from 1 RCT, 144 patients, NNT = 5 [95% CI, 3–18]), but not abatacept, improves renal function. Belimumab and rituximab do not increase the risk of serious intolerable adverse effects leading to treatment discontinuation. Rigerimod, blisibimod, sifalimumab, and anifrolumab show promising results in early RCTs, whereas epratuzumab and tabalumab have an unfavorable benefit-to-harm balance. Implications In adults with moderate to severe SLE despite conventional immunosuppressive agents, adjunctive belimumab in extrarenal SLE and off-label rituximab in lupus nephritis may offer additional modest benefits.

Summary B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) help in B cell activation, maintenance and plasma cell survival. B cell infiltration has been demonstrated in kidneys of patients with lupus nephritis (LN). Serum levels of BAFF and APRIL have shown inconsistent relationships with lupus disease activity. We evaluated urinary levels of BAFF and APRIL as biomarker for LN. Thirty-six patients with proliferative lupus nephritis (AN), 10 with active lupus without nephritis (AL) and 15 healthy controls (HC) were studied. APRIL and BAFF levels were measured in both serum and urine using enzyme-linked immunosorbent assay (ELISA). Urine levels were normalized for urinary creatinine excretion. Urine levels were correlated with conventional disease activity markers and histology. Levels were reassessed in 20 AN patients at 6 months after treatment with cyclophosphamide. Urinary APRIL (uAPRIL) and BAFF (uBAFF) levels were raised significantly in AN. uAPRIL, but not uBAFF, correlated moderately with renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in AN (r = 0·36, P

Cutaneous lupus erythematosus is a disfiguring and common manifestation in systemic lupus erythematosus, and the etiology of this predisposition for cutaneous inflammation is unknown. Here, we sought to examine the keratinocyte as an important source of IL-6 and define the mechanism for its increased production in cutaneous lupus erythematosus. Evaluation of discoid and subacute cutaneous lupus erythematosus lesions showed significant epidermal up-regulation of IL-6 compared with control via real-time PCR and immunohistochemistry. Keratinocytes from unaffected skin of lupus patients produced significantly more IL-6 compared with healthy control subjects after exposure to toll-like receptor 2, 3, or 4 agonists or exposure to UVB radiation. Pretreatment with type I interferons (IFN-α and IFN-κ) increased IL-6 production by control keratinocytes, and type I IFN blockade decreased IL-6 secretion by lupus keratinocytes. Secretion of keratinocyte-specific IFN-κ was significantly increased after toll-like receptor 2 and UVB treatment in lupus keratinocytes, and neutralization of IFN-κ decreased IL-6 production by lupus keratinocytes. Thus, lupus keratinocytes are primed for IL-6 hyperproduction in a type I IFN-dependent manner. Increased production of IFN-κ by lupus keratinocytes drives this response, indicating that IFN-κ may play a pathogenic role in cutaneous lupus erythematosus and serve as a target for treatment.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over the past 15 years. The results of Phase II trials were encouraging but rarely borne out by Phase III trials. Recent data, which are discussed in detail in this review, allowed belimumab - a monoclonal antibody against BLyS (B-lymphocyte stimulator) - to become the first biotherapy approved for use in SLE. Other molecules targeting B cells include the two anti-BLyS antibodies tabalumab and blisibimod; atacicept, which targets both BLyS and APRIL (a proliferation-inducing ligand); and the monoclonal antibody to CD22 epratuzumab. The rekindling of interest in the B-cell pathway has also driven new clinical research into rituximab, a monoclonal antibody targeting CD20 with evaluations of new strategies. A new and promising approach is the use of inhibitors of the type 1 interferon (IFN) pathway, of which the most promising is anifrolumab, a monoclonal antibody targeting the type 1 IFN receptor. In this review, we discuss study findings and their clinical relevance, present the most promising targets, and analyze possible explanations to negative results, such as inappropriate patient selection and treatment response criteria or the erratic use of high-dose glucocorticoid therapy.

Blisibimod is a potent and selective inhibitor of B cell activating factor (BAFF), a mediator of differentiation, maturation and survival of B cells. It has a unique tetravalent, 'peptibody' structure and resulting high potency, and is currently in clinical evaluation for the treatment of SLE. The importance of BAFF in the pathogenesis of systemic lupus erythematosus (SLE) is under intense investigation. The anti BAFF monoclonal antibody belimumab was approved by the FDA for the treatment of SLE.The general properties of blisibimod are reviewed including pharmacokinetic and pharmacodynamic properties in patients with SLE, efficacy and safety in the phase 2 PEARL-SC and open-label extension trials, and the focus in the ongoing phase 3 trial (CHABLIS-SC1) on the hypothesized 'responder' population. In addition, the rationale for evaluating blisibimod in patients with IgA nephropathy, a common nephritic disease for which there is no approved therapy, is presented.Blisibimod's unique tetravalent, peptibody structure and resulting high potency, and the deliberate focus of the Phase 3 clinical development program on the 'responder populations' identified in completed trials in SLE raise the possibility that blisibimod will become an important medication for treatment of SLE and IgA nephropathy.

Background/Aims Anti-C-reactive protein (CRP) antibody has been introduced as a potential biologic marker in Systemic lupus erythematosus (SLE). The aim of study is to evaluate the level of anti-CRP antibody in patients with SLE. METHODS This study investigated the relationship between levels of anti-CRP antibodies and disease activity markers, such as complement, anti-double-stranded DNA antibody, and SLE disease activity index in 34 patients with SLE. RESULTS The serum anti-CRP antibody levels of the patients with SLE were significantly higher than those of the healthy controls (11.3 ± 5.6 µg/mL vs. 9.1 ± 2.8 µg/mL). The percentages of the positive anti-CRP antibody were 52.9% in SLE and 27.8% in controls. Disease duration of SLE showed significant correlation with the anti-CRP antibody (r = 0.234, p = 0.026). However no significant relationship was observed between the levels of anti-CRP antibodies and disease activity markers. Conclusions These data show that the anti-CRP antibody levels of the patients with SLE were significantly higher than those of healthy controls. We observed that the presence of the anti-CRP anti-CRP antibody was not associated with disease activity of SLE.

This report evaluates the effects of blisibimod (A-623, AMG 623), a potent and selective inhibitor of B-cell activating factor (BAFF), on patient-reported fatigue and disease activity in the Phase 2b PEARL-SC clinical trial in patients with systemic lupus erythematosus (SLE). A total of 547 individuals who met the American College of Rheumatology (ACR) classification criteria for SLE, were positive for anti-double-stranded DNA or antinuclear antibodies, and had a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline, were randomized to receive placebo or blisibimod for at least 24 weeks. Patient self-reported fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and disease activity was evaluated using Physician’s Global Assessment, SELENA-SLEDAI, and British Isles Lupus Assessment Group Score. Statistically significant improvements in FACIT-Fatigue score were observed among individuals randomized to blisibimod, especially in the 200 mg QW group where favorable effects on disease activity with blisibimod compared to placebo were observed as early as Week 8. The mean improvement from baseline of 6.9 points at Week 24, compared with 4.4 points with placebo, met the criteria for minimal clinically important improvement difference defined for patients with SLE. Despite concomitant improvements in FACIT-Fatigue, SLE Responder Index (SRI) and SLE biomarkers (reported previously), FACIT-Fatigue score correlated only weakly with disease activity. While poor correlation between fatigue and disease activity is not new, the observation that correlation remains poor despite concurrent population improvements in disease and fatigue brings a new facet to our understanding of SLE.

Vitamin D is a steroid hormone that influences glucocorticoids and gonadal hormones, interfering with the immune system and estrogen-modulated cells. Therefore vitamin D deficiency is thought as a risk factor for several chronic inflammatory and autoimmune conditions.

Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE) in childhood affecting more than 80 % of patients. Treatment of this complication has undergone significant evolution in recent years. A series of randomized controlled trials has clarified the role of a variety of immunomodulating regimens including some novel biologic medications. This review touches on the major trials that have influenced practice and shaped current thinking about the treatment of proliferative lupus glomerulonephritis.

Hastalar ve yontemler: Aralik 2010 Aralik 2011 tarihleri arasinda, Kahire ve Ain Shaims Universite Hastanelerinden kolajen hastaligi olan 63 Misirli hasta [RA (n=21), SLE (n=21), BH (n=21)] ve beraberinde gorunusu saglikli olan 21 kisi kontrol grubu olarak calismaya dahil edildi. Katilimcilarin tumunun oykusu alindi, klinik muayenesi ve laboratuvar ve radyolojik incelemeleri yapildi ve hastalik aktivite skoru hesaplandi. Serum BAFF duzeyi, enzim bagli immunosorbent assay (ELISA) kiti ile olculdu.

To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE).A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches.After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs.CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.

OBJECTIVES This study aimed to compare the difference of the clinical and laboratory features of the patients between the combined systemic lupus erythematosus (SLE) and Sjogren syndrome (SLE-SS) and SLE only. MATERIALS AND METHODS A systematic literature search was performed to identify the articles as to SLE with SS between 1970 and May 2011. The demographics, pertinent clinical, and laboratory data were extracted from 6 publications, and a meta-analysis was performed. The pooled odds ratios and 95% confidence interval were computed for the variability of these parameters between SLE-SS and SLE. RESULTS A total of 6 studies were included, consisting of 2489 patients with SLE and 444 with SLE-SS, and the estimated prevalence of the latter was 17.8%. Patients with SLE-SS were older and more often had associated oral ulcers and arthritis. In contrast, proteinuria (odds ratio = 1.77; 95% confidence interval, 1.39-2.25; P < 0.0001) was more common in SLE alone than SLE-SS, and central nervous system involvement tended to be more common. Anti-double-stranded DNA antibodies were equally prevalent in both groups. Anti-SSA/Ro and anti-SSB/La antibodies were more frequent, and anti-Sm and anti-cardiolipin antibodies were less prevalent in SLE-SS than SLE alone. CONCLUSIONS There are significant variances in certain clinical and laboratory aspects between SLE-SS and SLE. This combined disease of SLE-SS has distinct features with relatively less major internal organ involvement but has more specific autoantibody profile and favorable clinical outcome.