Possible Role of Regulatory B Cells in Different Behçet's Disease Phenotypes and Therapies: First Report from Egypt.

BACKGROUND AND AIM: The data about the role of regulatory B cells (Breg) in Behcet Disease (BD) are scarce. We aimed to evaluate the frequency of total B lymphocytes and Breg cells in different BD phenotypes and therapies attempting to unravel their function. METHODS: This cross-sectional study included 35 BD patients and 39 healthy controls (HCs). The demographic data of the study subjects were collected including age and gender. Current medications including disease-modifying anti-rheumatic drugs (DMARDs) were recorded. All patients underwent testing for baseline laboratory investigations including full blood count, liver and kidney function tests, erythrocyte sedimentation rate (ESR) by Westergren blot and C-reactive protein (CRP). Measurement of the total B lymphocytes and their subtypes B regulatory lymphocytes by flow cytometric assay. Assessment of BD activity was done using the revised Behçet's Disease Current Activity Form (BDCAF) 2006 and Behçet's Syndrome Activity Score (BSAS) 1111111111. All participants were assessed for the presence of erectile dysfunction using the International Index of Erectile Function (IIEF-5 score), and for depression using the Beck Depression Inventory. RESULTS: A dramatic drop in the number of B cells, total and regulatory, was observed in the patients compared to the HCs. Regulatory cells (Bregs) tend to be upregulated with genital ulcers or vascular disease. Bregs but not B lymphocytes were associated with BSAS and ESR. Neither the total B lymphocytes nor the Bregs correlated with CRP or the sexual function or depression scores. Of all the used medications, low-dose aspirin was seen with markedly high Bregs proportions. CONCLUSION: This study supports the role of B cells in BD pathogenesis and strongly suggests a possible role for Bregs in the resolution of different BD manifestations.

B Cell Tetherin: A Flow Cytometric Cell-Specific Assay for Response to Type I Interferon Predicts Clinical Features and Flares in Systemic Lupus Erythematosus.

OBJECTIVE: Type I interferon (IFN) responses are broadly associated with autoimmune diseases, including systemic lupus erythematosus (SLE). Given the cardinal role of autoantibodies in SLE, this study was undertaken to investigate whether the findings of a B cell-specific IFN assay correlate with SLE activity. METHODS: B cells and peripheral blood mononuclear cells (PBMCs) were stimulated with type I IFN and type II IFN. Gene expression was analyzed, and the expression of pathway-related membrane proteins was determined. A flow cytometry assay for tetherin (CD317), an IFN-induced protein ubiquitously expressed on leukocytes, was validated in vitro and then clinically against SLE diagnosis, plasmablast expansion, and the British Isles Lupus Assessment Group (BILAG) 2004 score in a discovery cohort (n = 156 SLE patients, 30 rheumatoid arthritis [RA] patients, and 25 healthy controls). A second, longitudinal validation cohort of 80 SLE patients was also evaluated for flare prediction. RESULTS: In vitro, a close cell-specific and dose-response relationship between type I IFN-responsive genes and cell surface tetherin was observed in all immune cell subsets. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with type I IFN compared to types II and III IFNs. In patient samples from the discovery cohort, memory B cell tetherin showed the strongest associations with diagnosis (SLE:healthy control effect size 0.11 [P = 0.003]; SLE:RA effect size 0.17 [P < 0.001]), plasmablast numbers in rituximab-treated patients (R = 0.38, P = 0.047), and BILAG 2004. These associations were equivalent to or stronger than those for IFN score or monocyte tetherin. Memory B cell tetherin was found to be predictive of future clinical flares in the validation cohort (hazard ratio 2.29 [95% confidence interval 1.01-4.64]; P = 0.022). CONCLUSION: Our findings indicate that memory B cell surface tetherin, a B cell-specific IFN assay, is associated with SLE diagnosis and disease activity, and predicts flares better than tetherin on other cell subsets or whole blood assays, as determined in an independent validation cohort.

Cardiac Manifestations in Systemic Lupus Erythematosus: Clinical Correlates of Subclinical Echocardiographic Features.

OBJECTIVES: This study aims to correlate subclinical echocardiographic features with the clinical, laboratory, and therapeutic profiles of the patients to characterize risks for systemic lupus erythematosus (SLE) cardiac diseases. METHODS: The study included 59 SLE patients. Demographic data, disease characteristics, and current therapies were recorded, and the anthropometric measurements and routine laboratory tests were performed. The disease activity by the SLE Disease Activity Index-2K (SLEDAI2K) and the presence of metabolic syndrome (MetS) were assessed. Two-dimensional echocardiography was performed. RESULTS: The mean age of the patients was 31.3 ± 10.5 years, and the disease duration was 5.18 ± 4.1 years. 86.4% of the patients were females. Cardiac presentations by echocardiography were mainly mitral regurgitation (33.9%), tricuspid regurgitation (32.2%), mitral thickening (18.6%), aortic thickening (13.6%), pericardial effusion (13.6%), and pulmonary hypertension (8.5%) in order of frequency. The frequency of different echocardiographic findings with respect to other clinical phenotypes showed peaks with renal disease, MetS, and leukopenia. Components of MetS (triglycerides, high systolic blood pressure) and avascular necrosis were significant predictors for pericardial diseases (OR=1.011 CI 95% 1-1.022, p=0.046, OR=1.157 CI 95% 1.025-1.307, p=0.018, and OR=74.78 CI 95% 2.52-2215.76, p=0.013, respectively), and it is likely that hydroxychloroquine was protective against them. Age of the patients was a significant predictor for tricuspid regurgitation (OR=1.063 CI 95% 1.004-1.126, p=0.036). Mucosal ulcers were negative predictors for mitral thickening and regurgitation (OR=0.2 CI 95% 0.059-0.673, p=0.009). The use of corticosteroids appeared to protect against a number of valve lesions especially tricuspid regurgitation (OR=0.299 CI 95% 0.088-1.019, p=0.054). CONCLUSION: This study highlighted different echocardiographic features and identified clinical predictors of different cardiac pathologies aiming to determine patients at risk and improve the prognosis of SLE cardiac diseases.