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

Lookup NU author(s): Dr Vanessa Hogan, Philip Stocks, Professor Jaap Van Laar

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Abstract

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 metadata

Author(s): Teng YKO, Wheater G, Hogan VE, Stocks P, Levarht EWN, Huizinga TWJ, Toes REM, van Laar JM

Publication type: Article

Publication status: Published

Journal: Arthritis Research & Therapy

Year: 2012

Volume: 14

Issue: 2

Print publication date: 12/03/2012

Date deposited: 04/01/2013

ISSN (electronic): 1478-6354

Publisher: BioMed Central Ltd.

URL: http://dx.doi.org/10.1186/ar3770

DOI: 10.1186/ar3770

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