THE TIME COURSE OF CHANGES IN B LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS DURING THERAPY WITH BIOLOGICAL AGENTS

Abstract

Objective: to study the baseline level and time course of changes in peripheral blood B cell subpopulations in patients with systemic lupus erythematosus (SLE) versus the clinical manifestations of the disease during therapy with rituximab (RTM) and belimumab (BLM).Subjects and methods. 49 patients with a documented diagnosis of SLE and high and moderate SLEDAI-2K values were divided into three groups: 1) 40 patients received RTM, 2) 5 patients took BLM; 3) 4 patients had combination therapy (dual anti-B-cell therapy) with RTM + BLM. Peripheral blood B lymphocyte subpopulations were measured by multicolor flow cytometry using a panel of monoclonal antibodies against surface membrane markers of B lymphocytes; the patients underwent clinical immunological examination before therapy with biological agents and every 3 months during a year.Results and discussion. Patients with high SLE activity (SLEDAI-2K 18±5) and involvement of vital organs had generally higher levels of double negative memory cells (r = 0.52; p < 0.001) with relatively low counts of naive B cells (r=-0.54; p < 0.0007) than those without severe organ pathology (SLEDAI-2K 8±2). RTM therapy at 3 month of follow-up resulted in a noticeable decrease in the number of naive and double negative memory B cells and to a lesser extent in that of non-switched and switched memory B cell. A rapid recovery of the count of memory B cells and plasmablasts after a RTM cycle at 6 months after therapy initiation should be evaluated as a predictor of early exacerbation of SLE. There was a reduction in the clinical and laboratory signs of SLE activity, as well as inhibition of naive B cells, plasma cells, and plasmablasts in all the 5 patients receiving BLM at various stages of follow-up. Dual anti-B cell therapy most effectively reduced disease activity at 3 months, prolonged the achieved remission, contributed to the achievement and maintenance of a low B lymphocyte level at later stages of control, to the further decline in the number of plasmablasts and plasma cells, and prevented the synthesis of autoantibodies.Conclusion. Assessment of the time course of changes in peripheral blood B lymphocyte subpopulations provides new opportunities to identify impaired function and regulation of cellular immunity in patients with SLE, it may be a useful diagnostic parameter to monitor an autoimmune disease and a valuable tool to assess and predict a response.

Keywords

• b lymphocytes
• systemic lupus erythematosus
• treatment
• rituximab
• belimumab