Autoantibody-mediated regulation on B cell responses by functional anti-CD22 autoantibodies in patients with systemic sclerosis (137.42)

Abstract

Abstract Objectives. Studies have demonstrated that B cells play important roles in systemic sclerosis (SSc), especially through the gCD19/CD22 autoimmune loop h. In this study, we examined the presence and functional property of circulating autoantibodies reacting with CD22. Methods. Serum samples from 10 tight skin (TSK/+) mice and 50 SSc patients were assessed for anti-CD22 autoantibodies by enzyme-linked immunosorbent assays using recombinant mouse or human CD22. The association between anti-CD22 antibodies and clinical features was also investigated in SSc patients. Furthermore, the influence of SSc serum including anti-CD22 autoantibodies for CD22 tyrosine phosphorylation was examined by western blotting using phospho-tyrosine specific antibodies reacting with four major tyrosine motifs of CD22 cytoplasmic domain. Results. Anti-CD22 autoantibodies were positive in 80% of TSK/+ mice and in 22% of SSc patients. Patients positive for anti-CD22 antibodies showed significantly higher modified Rodnan skin thickness score compared with patients negative for anti-CD22 antibodies. Furthermore, anti-CD22 antibodies from patients' sera were capable of reducing phosphorylation of all four CD22 tyrosine motifs, while sera negative for anti-CD22 antibodies did not affect CD22 phosphorylation. Conclusions. A subset of SSc patients possessed autoantibodies reacting with a major inhibitory B cell response regulator, CD22. Since these antibodies can interfere CD22-mediated suppression onto B cell activation in vitro, SSc B cells produce functional autoantibodies that can enhance their own activation. This unique regulation may contribute to the autoimmune aspect of SSc.