Understanding the mechanistic basis in rheumatoid arthritis for clinical response to anti-CD20 therapy: the B-cell roadblock hypothesis.
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.
Silverman
Gregg J
GJ
Rheumatic Diseases Core Center, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA 92093-0663, USA. gsilverman@ucsd.edu
Boyle
David L
DL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D002986:Clinical Trials as Topic; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D008212:Lymphocyte Depletion; D051379:Mice; D000069283:Rituximab; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab