Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity

Arthritis Res Ther. 2012 Mar 12;14(2):R57. doi: 10.1186/ar3770.


Introduction: B-cell depletion has become a common treatment strategy in anti-TNF-refractory rheumatoid arthritis (RA). Although the exact mechanism of how B-cell depletion leads to clinical amelioration in RA remains to be elucidated, repetitive treatment with B-cell-depleting agents leading to long-term B-cell depletion has been reported to be beneficial. The latter has led to the hypothesis that the beneficial effects of B-cell depletion might act through their influence on pathogenic autoreactive plasma cells.

Methods: In this study, we investigated the effects of a fixed retreatment regimen with anti-CD20 mAbs on the humoral (auto)immune system in a cohort of therapy-refractory RA patients.

Results: Fixed retreatment led to long-term B-cell depletion in peripheral blood, bone marrow and, to a lesser extent, synovium. Also, pathologic autoantibody secretion (that is, anticitrullinated peptide antibodies (ACPAs)) was more profoundly affected by long-term depletion than by physiological protective antibody secretion (that is, against measles, mumps and rubella). This was further illustrated by a significantly shorter estimated life span of ACPA-IgG secretion compared to total IgG secretion as well as protective antibody secretion.

Conclusion: By studying plasma cell function during an extensive 2-year period of B-cell depletion, autoantibody secretion was significantly shorter-lived than physiologically protective antibody secretion. This suggests that the longevity of autoreactive plasma cells is different from protective long-lived plasma cells and might indicate a therapeutic window for therapies that target plasma cells.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / biosynthesis
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Autoantibodies / biosynthesis*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphocyte Depletion / methods*
  • Male
  • Middle Aged
  • Prospective Studies
  • Rituximab
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • Time Factors
  • Treatment Outcome


  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies
  • Rituximab