title: Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy.
abstract: OBJECTIVE
  To assess the presence and phenotype of B-lineage cells in the bone marrow (BM) of rheumatoid arthritis (RA) patients after rituximab therapy.
  
  
  METHODS
  Six patients were studied. BM aspirates were collected 3 months after the treatment and analysed using the four-colour flow cytometry.
  
  
  RESULTS
  CD19+ (B-lineage) cells in BM samples varied from 0.1 to 3.25% in the lymphoid gate. CD34+ cells varied from 1.23 to 4.86%. The proportion of CD34+ cells committed to the B-lineage varied between 0 and 42.19%. Pro-B-cells were undetectable in one case. The majority of B-cell precursors were pro-B-cells in Patients 5 and 6 (50 and 62% of CD19+ cells, respectively), pre-B-cells in Patients 3 and 4 (64 and 70%) and immature B-cells in Patient 1 (44%). Detectable CD20 expression on CD19+ cells was either low or absent. Plasma cells varied from 0.01 to 0.36% of the total nucleated cells. There was a trend towards longer duration of clinical response in patients with evidence of more complete depletion in BM.
  
  
  CONCLUSIONS
  In this small cohort of RA patients treated with rituximab, differences in proportion and phenotype of CD19+ BM cells were detected. These differences suggest variation in the degree of depletion achieved and correlate with time to relapse. Although pro-B-cells are not targeted directly by rituximab as they do not express CD20, the levels were unexpectedly low.
authors.affiliation: Centre for Rheumatology, University College London, London W1T 4JF, UK. maria.leandro@ucl.ac.uk
authors.forename: M J
authors.initials: MJ
authors.lastname: Leandro
authors.forename: N
authors.initials: N
authors.lastname: Cooper
authors.forename: G
authors.initials: G
authors.lastname: Cambridge
authors.forename: M R
authors.initials: MR
authors.lastname: Ehrenstein
authors.forename: J C W
authors.initials: JC
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000187:drug effects; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D000069283:Rituximab