Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis

Arthritis Rheum. 2006 Feb;54(2):613-20. doi: 10.1002/art.21617.

Abstract

Objective: To study the quantitative and phenotypic reconstitution of peripheral blood B cells and its relationship to the dynamics of clinical response in patients with rheumatoid arthritis (RA) following B cell depletion with rituximab.

Methods: Twenty-four patients with active RA treated with rituximab were studied. Flow cytometry with combinations of monoclonal antibodies to B cell and T cell subsets was used.

Results: The frequency and total number of CD19+ cells in the peripheral blood decreased a mean of 97% for more than 3 months in all but 1 patient following rituximab therapy. All B cell populations were depleted. More than 80% of residual B cells showed a memory or plasma cell precursor phenotype. B cell repopulation occurred a mean of 8 months after treatment and was dependent on the formation of naive B cells, which showed an increased expression of CD38 and CD5. During repopulation, increased numbers of circulating immature B cells, CD19+,IgD+,CD38(high),CD10(low),CD24(high) cells, were identified. Patients who experienced a relapse of RA on return of B cells tended to show repopulation with higher numbers of memory B cells. A small number of T cells and natural killer cells expressed low levels of CD20. These cells were depleted following rituximab therapy and returned to the circulation a mean of 5 months after treatment. No other significant changes were detected in the T cell populations studied.

Conclusion: Rituximab induced a profound depletion of all peripheral blood B cell populations in patients with RA. Repopulation occurred mainly with naive mature and immature B cells. Patients whose RA relapsed on return of B cells tended to show repopulation with higher numbers of memory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD / analysis
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocyte Count
  • Lymphocyte Depletion*
  • Male
  • Middle Aged
  • Rituximab

Substances

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