B-cell targeting in rheumatoid arthritis and other autoimmune diseases

• Published in: Nature Reviews: Immunology Vol. 6; no. 5; pp. 394 - 403
• Main Authors: Edwards, Jonathan C. W., Cambridge, Geraldine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2006; Nature Publishing Group
• Subjects: Animals; Antibodies; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Autoimmune diseases; Autoimmune Diseases - drug therapy; Autoimmune Diseases - immunology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; Clinical trials; Cytokines; Disease; Drug Delivery Systems; Feedback; Fuels; Humans; Immunology; Ligands; Lupus; Lymphocytes; review-article; Rheumatoid arthritis
• ISSN: 1474-1733; 1474-1741; 1365-2567
• DOI: 10.1038/nri1838

Key Points B-cell-depletion therapy has proved highly effective in rheumatoid arthritis and shows promise in several other autoantibody-associated diseases. B-cell-depletion therapy was designed with the aim of breaking a vicious cycle of the two-way B-cell–T-cell interaction. The CD20-specific monoclonal antibody rituximab is currently the main agent used in B-cell-depletion approaches. Clinical benefit from B-cell depletion follows changes in levels of autoantibodies more closely than circulating B-cell numbers and can continue for months or years after B cells have returned. Unwanted effects from immunosuppression seem to be minimal, although hypogammaglobulinaemia can occur after repeated therapy. Several methods of B-cell targeting are now under investigation, including neutralization of B-cell-activating factor (BAFF) and blockade of B-cell-selective kinases. Clinical trials of reagents that target B cells in individuals with autoimmune disease, in particular rheumatoid arthritis, have yielded highly promising results. Might such an approach bring us closer to the goal of re-establishing immune tolerance in these individuals? B-cell-targeted therapy for autoimmune disease emerged from theoretical proposition to practical reality between 1997 and 1998, with the availability of the B-cell-depleting monoclonal antibody rituximab. Since then, a score of autoantibody-associated disorders have been treated, with most convincing evidence of efficacy seen in subjects with rheumatoid arthritis. Several classes of B-cell-targeted agent are now under investigation. From the outset, a major goal of B-cell targeting has been the re-establishment of some form of immunological tolerance. In some subjects, the observed improvement of disease for years following therapy fuels hope that this goal might ultimately be achievable.