Journal
RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
Volume 36, Issue 2, Pages 325-+Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.rdc.2010.02.003
Keywords
B cell; Rheumatoid Arthritis; Biologic; Plasma cell
Categories
Funding
- NIH [U19 AI56390, R01 AI049660]
- Rochester Center for Biodefense of Immunocompromised Populations [N01-AI50029]
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Initially suggested by the presence of rheumatoid factor autoantibodies, multiple pathogenic roles for B cells (both antibody-mediated and antibody-independent) in rheumatoid arthritis (RA) now are supported by a growing body of experimental observations and human studies. The pathogenic significance of B cells in this disease also has been established conclusively by the proven benefit of Rituximab-induced B cell depletion in RA patients refractory to tumor necrosis factor (TNF) blockade. This article reviews the rationale for the use of B cell-targeting therapies in RA and discusses the caveats and limitations of indiscriminate B cell depletion as currently applied, ncluding incomplete depletion of pathogenic B cells and elimination of protective B cells. Finally, it presents alternative therapeutic strategies that exploit current knowledge of B cell activation, survival, and differentiation to provide more selective B cell and plasma cell targeting.
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