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Background:B cells have important functions in the pathogenesis of systemic autoimmune rheumatic diseases (SARDs).Objectives:The purpose of the research was to study the therapeutic option of Rituximab (RTM), a chimeric anti-CD20 antibody, in SARDs such as ANCA-associated systemic vasculitis (AAV), cryoglobulinemic vasculitis (СV), systemic lupus erythematosus (SLE), systemic sclerosis (SS), primary Sjögren syndrome (pSS) and IgG4-related disease (IgG4-RD).Methods:We present data on efficacy and safety of RTM in 515 patients (pts) with SARDs. 103 pts had AAV (58- granulomatosis with polyangiitis, GPA; 35- microscopic polyangiitis, MPA and 10- eosinophilic granulomatosis with polyangiitis, EGPA), 21 pts had CV, 167- SLE, 90- SS, 100- pSS, 34- IgG4-RD. Characteristics of pts and results of RTM treatment are present in Table. Mean follow-up duration after initiation of RTM was 25- 58 months.Results:The average cumulative RTM dose in all groups exceeded 2.4 g, 71% of pts received repeated RTM courses (0.5-1.0 g) every 4 – 12 months. Complete (good) clinical response was achieved in 70-93% pts, except for the SLE (49%- complete response, 32- incomplete and 19%- no response). Usage of repeated RTM courses increased the clinical efficacy and reduced the risk of recurrence. Despite the fact that the study population included a high percentage of pts with severe or refractory SARDs, total mortality rate was about 6% during the follow-up period, highest in CV and AAV (14-11%). In AAV and SLE infections constitute a significant proportion of serious adverse reactions (10-11%). Late-onset neutropenia was only in pts with AAV (12%) and SLE (3%).Conclusion:Treatment with RTM was highly effective in SARDs. In certain SARDs RTM safety profile of should be considered during treatment planning. Further studies of the targeted anti-B-cell therapy, including RTM efficacy and safety in SARDs, clarification of the indications and optimal RTM regimens are needed.Table.ParametersАAVCVSLESSpSSIgG4-RDGPA, MPAEGPAN pts9310211679010034Age, years41(16-67)50(24-71)53,6 + 2941(18-52)47(17-71)42 + 12,247,4 + 15,9Percentage of females56%90%52%92%75%97%60%Duration of disease, months*14(1-288)11(1-180)72(3-96)18(2-47)70(7-264)90(36-168)24(6-60)Cumulative RTM dose, g*3 (0,5-8)3 (1,5-5,5)4,7 + 3,82,4 (1,8±0,8)2,9(0,5-6)5,5 + 1,54 + 1,5Follow-up duration after the first RTM course, month*37(1–96)36(14-94)52(6-108)38(12-67)27(12-42)58(24-96)25(3-60)Clinical response, %Complete (good)93%90%71%49%70%92,5%77%Incomplete response6%10%29%32%24%6,5%23%No response1%0%-19%6%1%-Relapse8%30%--nd--Glucocorticoids dose, mg/day*:Before RTMAfter RTM30(5–60)5(0-10)20(7,5-50)7,5(5-10)4,4(0-24)1,5(0-4)28(15-40)7,5(5-15)12(0-25)9(0-15)7,5(0-40)1,2510(2,5-40)0,5Immunosuppressants% pts before RTM72%90%38%65%43%44%40%% pts after RTM43%70%5%46%50%8%10%Infusion-related reactions,9%20%24%4%2%10%3%including severe-10%-0,6%1%1%-Pts with serious adverse reactions,26%40%5%14%2%5%3%including: infections,11%10%-10%2%5%3%neutropenia10%20%-3%---Deceased pts during the follow-up11%-14%5%6%2%-*Data are provided in the following format: median & min-max range in the bracketsDisclosure of Interests:None declared

The detection in serum of monospecifc antibodies that induce a dense fne-speckled fluorescence when interacting with the DFS70 / LEDGF / p75 nuclear antigen is negatively associated with the development of systemic autoimmune rheumatic diseases (SARD) and increases the diagnostic specifcity of the screening study of antinuclear antibodies (ANA) using indirect immunofluorescence on HEp-2 cells (IIF-HEp-2). The results of assessing the clinical signifcance of anti-DFS70 antibodies vary depending on the test systems and the selection of patient groups. The aim of this work is to study the frequency of detection of monospecifc anti-DFS70 antibodies in blood serum in healthy individuals and patients with SARD. Sera of 74 healthy donors and 59 patients with SARD were studied (27 – systemic lupus erythematosus – SLE, 15 – Sjogren's syndrome – SjS, 17 – rheumatoid arthritis – RA). Classical antinuclear antibodies (ANA) and anti-DFS70 antibodies were determined by IIF using a mixture of standard and genetically engineered DFS70-KO HEp-2 cells that do not express DFS70 / LEDGF / p75 as a substrate. 14.9% of healthy donors and 83.1% of SARD patients (96.3% – SLE, 100.0% – SS, 47.1% – RA) were seropositive for antinuclear factor (ANF). Classical ANA with homogeneous, speckled, nucleolar, cytoplasmic, mixed types of fluorescence and the absence of anti-DFS70 antibodies were found in all ANF-positive patients with SARD and in 8.1% of healthy donors. Monospecifc anti-DFS70 antibodies without classical ANA were detected in 6.8% of healthy individuals and were absent in SARS. Among ANF-positive healthy donors, the frequency of isolated detection of anti-DFS70 antibodies was 45.5%. The detection of monospecifc anti-DFS70 antibodies can be considered as a potential predictive marker for excluding the diagnosis of SARD in ANF-positive patients with no or unclear clinical signs of these diseases.

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Introduction:The adverse experience in childhood (parental deprivation mostly) (AEC) has an important role in predisposing to mood and immuno-inflammatory rheumatic disorders in adults via chronic stress mechanisms. The primary Sjögren's Syndrome (SS) - a chronic, systemic autoimmune disease, which has some common pathogenic links with stress-related mental disorders.Objectives/Aims:To evaluate the AEC and MD presentation in SS patients.Methods:80 inpatients (mean age 46,2+12,3 yrs) suffering SS were enrolled in the study. MD were diagnosed in accordance with ICD-10 criteria. The severity of depression, anxiety, stress were measured with HADS, MADRS, HAM-A, PSS-10.Results:The AEC had 78,7% of SS patients (recurrent events – 32,5%). Patients with AEC had an increased risk of developing dysthymia (OR=1,34; 95% CI=0,26–6,83) and depressive episode (OR=1,75 (0,35–8,65)) in adults. Recurrent depression was not revealed in patients with ACE. However, patients with AEC had no reliable differences in the MADRS, HAM-A, HADS, PSS-10 compared to patients without AEC. Patients with AEC had an increased risk of suicide attempts (OR=2,15; (0,25–37,2)) and suicidal thoughts (OR=4,58; (0,25–18,5)). The reliable correlations of the severity of SS symptoms (dry eyes/mouth, lymphoma) and AEC have not been confirmed. Patients with AEC had early onset SS (33,6±13,0 vs 38,1±14,2) and MD (28,4±12,6 vs 34,1±13,5) than patients without AEC.Conclusion:AE? is a significant risk factor for depression and suicidal thoughts and attempts in patients suffering SS.