Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis

Arthritis Rheum. 2011 Dec;63(12):3692-701. doi: 10.1002/art.30599.


Objective: To examine blood B cell subsets in patients with rheumatoid arthritis (RA) prior to B cell depletion therapy and to assess their potential as predictors of clinical response to rituximab (RTX).

Methods: Blood B cell subsets were assessed by flow cytometry in 208 RA patients included in an RTX retreatment study (assessed prior to RTX treatment) and in 47 age-matched controls. Expression of BAFF receptor (BAFF-R) on B cells and serum B cell biomarkers was also measured. B cell subsets and BAFF-R expression were compared between RA patient and control populations. Univariate and multivariate analyses were performed to identify baseline factors associated with a European League Against Rheumatism response 24 weeks after 1 cycle of RTX.

Results: Mean ± SD counts of both CD27- naive and CD27+ memory B cells were decreased in RA patients (188.6 ± 121.4/mm(3)) compared with controls (257.3 ± 154.1/mm(3)) (P = 0.001) and were partially restored in patients treated with methotrexate (MTX) plus anti-tumor necrosis factor compared with patients treated with MTX alone. Within the CD27+ memory B cells, the CD27+IgD- switched memory subtype was selectively decreased, irrespective of treatment. The frequency of CD27+ memory B cells correlated inversely with levels of several B cell activation biomarkers in RA. Serum BAFF level and BAFF-R expression was comparable in RA patients and controls. A low baseline CD27+ memory B cell frequency was associated with a greater clinical response to RTX (odds ratio 0.97 [95% confidence interval 0.95-0.99], P = 0.0015).

Conclusion: In B cell depletion therapy-naive RA patients, a low frequency of CD27+ memory B cells correlated with levels of serum B cell activation biomarkers and may predict response to RTX. These results suggest that low memory B cell frequency may be indicative of a B cell-driven RA subtype that is more sensitive to B cell depletion therapy.

Trial registration: NCT01126541.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • B-Cell Activation Factor Receptor / metabolism
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / pathology*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lymphocyte Depletion
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Predictive Value of Tests
  • Rituximab
  • Treatment Outcome
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism


  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • B-Cell Activation Factor Receptor
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Rituximab
  • Methotrexate

Associated data