title: Long-term repopulation of peripheral B-cell subsets after single and repeated rituximab infusions in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Roll
authors.affiliation: Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
authors.forename: Zafar
authors.initials: Z
authors.lastname: Mahmood
authors.affiliation: Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
authors.forename: Khalid
authors.initials: K
authors.lastname: Muhammad
authors.affiliation: Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Feuchtenberger
authors.affiliation: Charité, Universitätsmedizin Berlin and DRFZ Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.affiliation: Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Tony
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab