AB0025 Evolution of Regulatory B Cells under Treatment by Biologics in Rheumatoid Arthritis

2016 
Background In clinical daily practice, the response to biologics is unpredictable in patients with rheumatoid arthritis (RA) and there is a crucial need for biomarkers of response. Objectives The main objective of our study is to describe the evolution of regulatory B cells (Bregs) in patients with RA treated with biologics and to investigate whether there is a correlation between the rate of Bregs and the clinical response. Methods This was a propective single-center pilot study, descriptive and not randomized. Patients were included with RA fulfilling the ACR/EULAR 2010 criteria, with an active disease according to the DAS28 score despite treatment, and in whom initiation or switch of a biologic except rituximab was required. Acontrol group of patients without any autoimmune disease or immune dysfunction was also assessed. B and T lymphocytes whole blood phenotyping, as well as an analysis of the production of IL-10 were performed by multicolor flow cytometry (FCM) in both patients and controls at baseline (M0) and in patients after 1 (M1), 3 (M3) and 6 (M6) months of treatment. CD24hiCD38hi CD24hiCD27+ subpopulations were selected for the phenotypic study of Bregs (24–38 and 24–27 Breg). The primary endpoint was the rate and absolute value of Bregs as a percentage and absolute value measured at each time of the study and compared with disease activity. Results Thirty patients and 15 controls were included in this study. Nowadays, phenotypic analysis was performed at baseline in all patients, but only in 15 patients at M1 and 13 patients at M3. The complete data will be available for the EULAR congress. There was an increase in circulating 24–38 Bregs between M1 and M3 (p=0.06) whatever the biologic prescribed. At baseline, the 24–38 Bregs were significantly lowered in patients compared to controls in percentage and absolute value (p=0.001 and p=0.013 respectively). The DAS28 remission and EULAR response at M3 were associated with a quantitative increase of 24–38 and 24–27 Breg at baseline compared to the values of the non-responders patients. Thus, a high initial rate of 24–27 and 24–38 Breg seemed associated with a good clinical response and an EULAR remission at 3 months. The rate of CD19 + B producing IL-10 obtained by PBMC culturing seemed lower in controls as compared to the patients. Conclusions We observed an increase of Bregs under treatment by biologics and a quantitative decrease in Bregs in patients with active RA compared to healthy subjects and patients with inactive disease. Thus, Bregs could be a marker of activity of the disease and their level may represent a potential predictor of the therapeutic response. Full data are required to confirmed these preliminary results. Disclosure of Interest None declared
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