Interaction of anti-DNA antibodies with synthetic polyanionic antigens

Abstract

Autoantibodies to DNA (anti-DNAab), found primarily in systemic lupus erythematosus (SLE), cross-react with a variety of antigens. The binding of these antibodies to naturally occurring mucopolysaccharides such as heparan and chondroitin sulfates has led to the suggestion that anti-DNAab have specificity for a polyanionic epitope. In this study, to avoid the use of endogenous immunogens to which humans may have become sensitized, we have used the synthetic polyanions, dextran sulfate (DS), polyvinyl sulfate (PVS) and the semi-synthetic antigen, pectic acid (PA) to evaluate this hypothesis using SLE sera ( n = 15) and sera from healthy individuals (controls; n = 15, age and sex matched to SLE group). Inhibition of binding with 125I-DNA was optimal at 1 mg/ml for DS and PVS, and resulted in significant inhibition of binding by both SLE and control sera of native DNA ( P < 0.01, each group); no inhibition was observed with PA, nor was a significant inhibition observed with any antigen on binding of SLE or control sera groups to denatured DNA. We conclude that while on quantitative grounds reaction of anti-DNAab with polyanions may not be clinically relevant, it is clear that, unlike polycarboxylates (e.g. PA), poly-sulfated polymers, whether aliphatic, as in the case of PVS, or glycosidic, such as DS, react with a subpopulation of anti-DNAab in such a manner as to block significantly the ability of these antibodies to bind DNA.