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Residual inflammation after rituximab treatment is associated with sustained synovial plasma cell infiltration and enhanced B-cell repopulation
  1. Y K Onno Teng (y.k.o.teng{at}lumc.nl)
  1. Leiden University Medical Center, Netherlands
    1. E W Nivine Levarht (e.w.n.levarht{at}lumc.nl)
    1. Leiden University Medical Center, Netherlands
      1. René EM Toes (r.e.m.toes{at}lumc.nl)
      1. Leiden University Medical Center, Netherlands
        1. Tom WJ Huizinga (t.w.j.huizinga{at}lumc.nl)
        1. Leiden University Medical Center, Netherlands
          1. Jacob M van Laar (j.m.van-laar{at}newcastle.ac.uk)
          1. Newcastle University, United Kingdom

            Abstract

            Objective To investigate the clinical effects of Rituximab treatment in relation to immunological effects of Rituximab on tissue-derived B-lineage cells and repopulation of circulating B-cells.

            Methods: Twenty-four RA patients were treated with 2x1000mgr Rituximab and assessed clinically at 4, 12, 18 and 24 weeks using disease activity scores of 44 joints (DAS44). Synovial biopsies were analyzed with immunohistochemistry at baseline and 12 weeks after treatment. Peripheral blood mononuclear cells were analyzed by high sensitivity flowcytometry at all timepoints.

            Results: We dichotomized the cohort in patients who achieved a low disease activity (DAS44<2.4: LoA-group) and those with persistent disease activity (DAS44>2.4: HiA-group) at any time after Rituximab treatment. At baseline, the LoA-group had significantly lower DAS44-scores (median 3.33 [range 2.84-4.23]) than the HiA-group (median 3.73 [range 3.03-5.23]; p=0.022) and significantly less histological inflammation in synovium (median 6.7 [1-15] versus 16.6 [4-22]; p=0.036). DAS44-scores before and after Rituximab treatment were associated with synovial infiltration of CD79a+ CD20- B-cells, morphologically resembling plasma cells. Following treatment with Rituximab, the LoA-group had significantly reduced repopulation of circulating pre-switched IgD+ B-cells (median 0.044% [range 0.002-0.66] versus 0.45% [range 0.07-9.47]; p=0.006) and post-switched CD27+ B-cells (median 0.17% [range 0.04-0.39] versus 0.67 [0.08-2.05]; p=0.005) compared to the HiA-group.

            Conclusion: The present study demonstrated that a low disease activity state following Rituximab was associated with reduced infiltration of CD79a+ CD20- plasma cells in synovium and reduced B-cell repopulation.

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