34 Ann. N.Y. Acad. Sci. 1050: 34–39 (2005). © 2005 New York Academy of Sciences. doi: 10.1196/annals.1313.004 BAFF Overexpression Is Associated with Autoantibody Production in Autoimmune Diseases JACQUES-OLIVIER PERS, a CAPUCINE DARIDON, a VALÉRIE DEVAUCHELLE, b SANDRINE JOUSSE, b ALAIN SARAUX, b CHRISTOPHE JAMIN, a AND PIERRE YOUINOU a a Department of Immunology and b Department of Rheumatology, Brest University Medical School, Brest, France ABSTRACT: The B-cell activity factor (BAFF) acts as a positive regulator of B- cell function. To gain further insight into the understanding of B-cell hyper- activity in autoimmune diseases, the serum level of BAFF was determined in 43 systemic lupus erythematosus (SLE) patients, 58 primary Sjögren’s syndrome (pSS) patients, 28 rheumatoid arthritis (RA) patients, and 68 normal control subjects using an in-house sandwich ELISA. A commercial kit was used to detect soluble CD23 (sCD23) reflecting B-cell activation. In-house assays for the detection of autoantibodies also were used. We found an increased level of BAFF in SLE, pSS, and RA sera compared with normal subjects (respectively, 10.6 ± 8.5, 15.8 ± 12.9, 9.7 ± 1.5 ng/mL vs. 4.6 ± 2.9 ng/mL, P < .001). sCD23 released on B-cell activation also was found to be elevated in SLE, pSS, and RA compared with normal sera. However, no correlation was found between the circulating BAFF and the level of sCD23. By contrast, we observed that high levels of BAFF were associated with the presence of autoantibodies (anti– double-stranded DNA antibodies in SLE, anti-SSA antibodies in pSS, and rheumatoid factors in RA). Our data suggest that BAFF is influential in driving antibody production rather than activation of the B lymphocytes in autoimmune diseases. KEYWORDS: BAFF; autoantibodies; systemic lupus erythematosus; Sjögren’s syndrome; rheumatoid arthritis Polyclonal hyperglobulinemia is a common aspect in non-organ-specific auto- immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren’s syndrome (pSS). 1 The profile of autoantibodies in any individual disease is relatively specific, indicating unique pathogenic features for each disease. Nevertheless, the global elevations in serum immunoglobulins (Igs) observed across patients with different connective diseases suggest that common factors contribute to this dysregulation. One of the most potent is the B-cell activity Address for correspondence: Professor Pierre Youinou, Laboratory of Immunology, Brest University Medical School Hospital, BP824, F29609, Brest, France. Voice: +(33)-2-98-22-33- 84; fax: +(33)-2-98-22-38-47. youinou@univ-brest.fr