BAFF Overexpression Is Associated with Autoantibody Production in Autoimmune Diseases

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 hyperactivity 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.

Is minor salivary gland biopsy more than a diagnostic tool in primary Sjo¨gren׳s syndrome? Association between clinical, histopathological, and molecular features: A retrospective study

“…BAFF overexpression, observed in serum, saliva, and MSGs of pSS patients, particularly those with GCs, rescues auto-reactive cells from depletion in the periphery, leading to higher number of mature auto-reactive B cells [24,[37][38][39][40][41].…”

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

“…Several cross-sectional studies showed that approximately 30% of SLE patients had significantly elevated circulating levels of BAFF/BLys [Cheema et al 2001;Zhang et al 2001]. Elevated BAFF/BLys levels appeared to correlate with increased total IgG and autoantibody (particularly anti-dsDNA) levels [Cheema et al 2001;Pers et al 2005], and, in some studies, with increased disease activity (as measured by SLEDAI) [Becker-Merok et al 2006]. A recent study has shown that excessive productions of IFNγ by activated T cells may be responsible for the induction of BAFF/BLyS production by monocytes and macrophages in lupus patients [Harigai et al 2008].…”

BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands

“…Elevated levels of BAFF have been detected in serum and synovial fluid samples from patients with rheumatoid arthritis (RA), and it was recently demonstrated that overproduction of BAFF by dendritic cells and macrophages may play a crucial role in the pathogenesis of experimental arthritis (8,9).…”