Crossreactivity of Human Anti-dsDNA Antibodies to Phosphorylcholine: Clues to Their Origin

Abstract

The presence of anti-double stranded DNA (dsDNA) antibodies is a serological diagnostic feature of systemic lupus erythematosus (SLE), an autoimmune rheumatic disorder. Studies by several investigators have suggested that a response to a microbial antigen can lead to the induction of SLE-like autoimmunity, in both humans and mice, since anti-dsDNA antibodies have been shown to crossreact with foreign antigens. In particular, anti-DNA antibodies have been shown to crossreact with phosphorylcholine (PC), a dominant epitope on pneumococcal cell wall polysaccharide. We have investigated the binding characteristics of human polyclonal anti-DNA antibodies from the sera of SLE patients. In this study we show that the DNA binding of polyclonal serum derived antibodies can be partially inhibited by phosphorylcholine (PC). The binding of affinity-purified anti-DNA antibodies from the sera of patients with SLE was also found to be inhibited by PC. We further demonstrated that the serum IgG1 (T dependent) anti-DNA response was more likely to crossreact with PC than the IgG2 (T independent) response to DNA. The studies suggest there may be a T dependent and T independent response to DNA with the T dependent response displaying more crossreactivity with microbial antigen.