AB0033 B Cell Depletion by Rituximab in Lymphocyte Subpopupulations from Peripheral Blood in Patients with Rheumatoid Arthritis
Authors: L. Merino Meléndez, J. Lόpez Lόpez, I. Llorente, S. Castañeda Sanz, F. Herrera, T. Velasco, J. Alvaro-Gracia, R. García-Vicuña, C. Muñoz-Calleja, I. González-Άlvaro
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic disease that leads to inflammation of the joints and other tissues. Rituximab (Rtx) is a therapeutic monoclonal antibody directed against CD20 that induces an important depletion of B cells. Although little is known about how it modifies the homeostasis of lymphoid subpopulations, it has been successfully used in RA. <h3>Objectives</h3> The objective of this study was to know whether Rtx modifies the ratio of the different lymphocyte subpopulations from peripheral blood in RA patients. <h3>Methods</h3> We studied 62 RA patients that underwent treatment with Rtx because of active RA and failure to at least one previous anti-rheumatic drug. The patients were divided into those naïve for Rtx treatment (RtxN n=21) and those who had received at least one previous cycle of treatment with Rtx (RtxS n=41). Peripheral blood samples for lymphoid subpopulation analysis were obtained at different times in both RtxN and RtxS patients: before the first infusion of Rtx (baseline) and at 3, 6 and 8 months after it (T3, T6 and T8 respectively). We studied different combinations of molecules that allowed us to calculate the percentage of T cell subpopulations, including memory and naïve T cells, effector and central memory T cells, follicular T helper cells and regulatory T cells. In the case of B cells, we analyzed memory and naïve B cells, Marginal Zone B cells, follicular B cells and plasmablasts B cells, at each visit. Differences between groups were analyzed by ANOVA test. <h3>Results</h3> At baseline, there was a significant difference in the percentage of a considerable number of B cell subsets. In particular, we observed an important decrease in memory B cells and an increase in follicular B cells. We also detected an increase in CD38+CD24+CD10+ B cells in RtxS. Regarding T cell subpopulations, we only observed a significant decrease in Th17 cells and in follicular T helper cells in RtxS. During the follow up period, the differences in T cells observed at baseline became much smaller presumably because of the effects of Rtx. At T3 only CD4 + T cells and memory T cells, defined by the absence of CD62L, were significantly lower in RtxS. At T6, we observed an increase in the CD8+CCR6- CXCR6- subpopulation in RtxS. At T8, as some patients had already repopulated B cell subsets, we found differences in B cells, and we detected a decrease in the CD38- B cell population. Taking into account the T cell population, we noted an increase in total T cells in RtxS with a significant decrease in effector-memory T cells. <h3>Conclusions</h3> Depletion of B cells through Rtx treatment leads to a profound change in the subpopulations of peripheral blood B cells, due to repopulation, and also of T cells. This suggests that mature B cells play a relevant role in the homeostasis of T cells. <h3>Acknowledgements</h3> * L. Merino and J. Lόpez have contributed equally to this work. <h3>Disclosure of Interest</h3> None declared