B cell therapies for rheumatoid arthritis: beyond B cell depletion.
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.
Calero
Ismael
I
Internal Medicine Department, Hospital Virgen de la Luz, Calle de la Hermandad de Donantes de Sangre, Cuenca 16002, Spain.
Nieto
Jose Antonio
JA
Sanz
Iñaki
I
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D010950:Plasma Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab