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Understanding the mechanistic basis in rheumatoid arthritis for clinical response to anti‐CD20 therapy: the B‐cell roadblock hypothesis
Author(s) -
Silverman Gregg J.,
Boyle David L.
Publication year - 2008
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2008.00627.x
Subject(s) - cd20 , rituximab , rheumatoid arthritis , immunology , medicine , pathogenesis , antibody , b cell , arthritis , pathology , cancer research
Summary: With the clinical introduction of the anti‐CD20 antibody rituximab for the treatment of rheumatoid arthritis (RA), B‐cell‐targeted therapy has become an accepted strategy for the treatment of a common chronic inflammatory disease. From recently reported synovial biopsy studies, we can begin to develop a pathophysiologic model of the sequential synovial cellular and molecular changes induced by rituximab infusions. These findings may explain how the rapid and early depletion of CD20‐bearing B cells may later lead to the more far‐reaching histopathologic changes that are associated with clinical responsiveness. Anti‐CD20 antibody treatments may therefore affect the representation of not only mature B lymphocytes and differentiated immunoglobulin‐secreting cells but also infiltrating cells such as synovial macrophages and fibroblast‐like synoviocytes. In light of the known prominence of recirculating memory B cells in RA pathogenesis, we propose that clinical efficacy also in part reflects the development of an effective blockade of the recirculation of potentially pathologic B cells that may prevent reseeding of pathologic synovial ectopic lymphoid tissues.