Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis

IntroductionIn the present study we evaluated changes in the B cell phenotype in peripheral blood and bone marrow (BM) of patients with rheumatoid arthritis (RA) next anti-CD20 treatment using rituximab. Methods: Blood and BM samples were obtained from 37 patients with RA prior to rituximab treatment. Ten of these patients were resampled 1 month following rituximab, 14 patients after 3 months and the remaining 13 patients were included in the long-term follow up. B cell populations were characterized by CD27/IgD/CD38/CD24 expression. Results: One and three months following rituximab BM retained up to 30% of B cells while circulation was completetly depleted of B cells. Dialogue of the remaining BM B cells showed prevalence of immature and/or transitional B cells (CD38++CD24++) and CD27+IgD- recollection cells, while IgD+ cells were completely depleted. A compelling decrease of CD27+ cells in BM and in circulation was observed long after rituximab treatment (mean 22 months), while levels of naive B cells in BM and in circulation were increased. The levels of rheumatoid part decline after rituximab treatment however returned to baseline levels at the date of retreatment. Conclusions: Anti-CD20 treatment achieves a depletion of IgD+ B cells shortly after the treatment. At the drawn out term supersede up, a reduction of CD27+ B cells was observed in blood and BM. The prolonged inability to up-regulate CD27 may inhibit the renewal of honour B cells. This lessening of CD27+ B cells does not prevent autoantibody production suggesting that mechanisms regulating the formation of car reactive clones are not disrupted by rituximab.

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