A STUDY ON CROSS-REACTIVITY OF ANTI-DNA ANTIBODY WITH GLYCOSAMINOGLYCANS

To study the pathogenesis of lupus nephritis, the cross reactivity bet ween anti-DNA antibody and glycosaminoglycans (GAGs) was investigated. Monoclonal anti-DNA antibodies were obtained from hybridomas by the f usion of MRL/lpr/lpr splenocytes with murine myeloma cells. Some of th ese monoclonal anti-DNA antibodies showed cross reactivity with GAGs, such as hyaluronic acid, chondroitin sulfate and heparan sulfate. To e lucidate the mechanism of cross reactivity, inhibition assays with pro panol and polyethylenimine (PEI), a cationic agent, were carried out. Increase of the concentration of PEI (0.6-2.0 % vol/vol) resulted in a dose dependent decrease in the binding ability of anti-DNA antibody t o GAGs. Propanol, an organic reagent which disrupts the van der Waals bonds between epitopes and paratopes, showed little inhibitory effect on the binding activity of monoclonal anti-DNA antibody to GAGs. These results indicate that the binding of anti-DNA antibody to GAGs is due to a charge interaction rather than van der Waals forces. Anti-DNA an tibody which can react with GAGs in the glomerular basement membrane s eems to play an important role in the pathogenesis of lupus nephritis.