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AB0033 B Cell Depletion by Rituximab in Lymphocyte Subpopupulations from Peripheral Blood in Patients with Rheumatoid Arthritis
  1. L. Merino Meléndez1,
  2. J. Lόpez Lόpez2,
  3. I. Llorente1,
  4. S. Castañeda Sanz1,
  5. F. Herrera2,
  6. T. Velasco1,
  7. J. Alvaro-Gracia1,
  8. R. García-Vicuña1,
  9. C. Muñoz-Calleja2,
  10. I. González-Άlvaro1
  1. 1Rheumatology
  2. 2Immunology, H.U. la Princesa, Madrid, Spain

Abstract

Background 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.

Objectives The objective of this study was to know whether Rtx modifies the ratio of the different lymphocyte subpopulations from peripheral blood in RA patients.

Methods 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.

Results 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.

Conclusions 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.

Acknowledgements * L. Merino and J. Lόpez have contributed equally to this work.

Disclosure of Interest None declared

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