Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy

Rheumatology (Oxford). 2007 Jan;46(1):29-36. doi: 10.1093/rheumatology/kel148. Epub 2006 May 30.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / metabolism
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • B-Lymphocyte Subsets / drug effects*
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / immunology
  • Female
  • Flow Cytometry / methods
  • Follow-Up Studies
  • Humans
  • Immunophenotyping
  • Lymphocyte Count
  • Lymphocyte Depletion / methods*
  • Male
  • Middle Aged
  • Plasma Cells / drug effects
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antirheumatic Agents
  • Rituximab