Expression of B Cell Activating Factor (BAFF) and BAFF-binding Receptors in Rheumatoid Arthritis

Abstract

It is widely accepted that B cells play an essential role in the pathogenesis of rheumatoid arthritis (RA). B cell involvement is well documented in the presence of detectable autoantibodies in the majority of patients, in particular, rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA), which can be detected many years before development of clinical disease, indicating that autoreactive B cell clones are involved in disease induction1. B cell depletion therapy with rituximab (anti-CD20) is effective in treating RA, proving an essential role for B cells in disease persistence2. Although B cell depletion therapy can induce longterm responses in a small number of patients, almost all patients eventually relapse. There is therefore much interest in finding out whether analysis of B cell-related factors can guide the development of treatment strategies and/or prediction of disease flare. The cytokine B cell activating factor (BAFF; also known as BLyS) plays an essential role in B cell survival and homeostasis. BAFF binds to 3 different receptors: BAFF-R, TACI, and BCMA. Expression of the different BAFF-binding receptors varies in distinct subsets of B cells, and their expression is coordinated and intimately related to maturation and activation status3. In the study by Moura, et al in this issue of The Journal 4, gene expression of molecules related to B cell survival and differentiation were studied in peripheral blood mononuclear cells (PBMC) in a small group of patients with very early RA (VERA; i.e., < 6 weeks of symptoms) and compared with other patients with RA at different stages [early RA (ERA) > 6 weeks and < 1 year duration; and established RA > 1 year duration], with patients with other forms of early arthritis (EA), and with healthy controls (HC). Patients with established RA were all taking methotrexate, … Address correspondence to Dr. M.J. Leandro, Centre for Rheumatology Research, Division of Medicine, University College London, Rayne Building, 5 University Street, London WC1E 6JF, UK; E-mail: maria.leandro{at}ucl.ac.uk