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Long-term repopulation of peripheral B-cell subsets after single and repeated rituximab infusions in patients with rheumatoid arthritis


1, 2, 3, 4, 5, 6

 

  1. Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
  2. Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
  3. Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
  4. Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
  5. Charité, Universitätsmedizin Berlin and DRFZ Berlin, Germany.
  6. Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.

CER7847
2015 Vol.33, N°3
PI 0347, PF 0353
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PMID: 25897997 [PubMed]

Received: 14/08/2014
Accepted : 19/12/2014
In Press: 16/04/2015
Published: 22/06/2015

Abstract

OBJECTIVES:
B-cell depletion using rituximab (RTX) has proven efficacy in patients with RA. Long-term effects on the B-cell system after single and repeated treatments are sparse. Our aim was to study the effect of multiple courses of rituximab to evaluate its impact on repeated B-cell re-population capacity.
METHODS:
Two cohorts, altogether 20 patients with RA were included in an open label extension study with RTX. Cohort 1 received one cycle RTX and was followed for up to 7 years. In cohort 2 patients were studied under up to 5 cycles of RTX. Immunophenotyping was performed before therapy and during follow-up.
RESULTS:
After a single therapy with RTX (cohort 1) the frequency of pre-switch (MZ-like) B cells were significantly reduced during the follow-up of 7 years and absolute numbers slowly repopulated to nearly 50% of baseline value without numerical normalisation. The acquisition of mutations in Ig receptors of pre-switch (MZ-like) memory B cells was also significantly reduced 10 years after one course. In contrast, absolute numbers of (classical) post-switch B cells tended to normalise to baseline values after 7 years. Analysing B-cell repopulation capacities after multiple cycles revealed (cohort 2) a comparable repopulation pattern after each cycle with no substantial further impact on memory B cells.
CONCLUSIONS:
A single therapy with RTX leads to long-term changes in the memory B-cell compartment particularly in pre-switch memory B cells. Multiple cycles of RTX show a comparable repopulation pattern after each cycle with no additional cumulative effect on memory B cells.

Rheumatology Article