A study on cross-reactivity of anti-DNA antibody with glycosaminoglycans.
To study the pathogenesis of lupus nephritis, the cross reactivity between anti-DNA antibody and glycosaminoglycans (GAGs) was investigated. Monoclonal anti-DNA antibodies were obtained from hybridomas by the fusion of MRL/lpr/lpr splenocytes with murine myeloma cells. Some of these monoclonal anti-DNA antibodies showed cross reactivity with GAGs, such as hyaluronic acid, chondroitin sulfate and heparan sulfate. To elucidate the mechanism of cross reactivity, inhibition assays with propanol 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 to 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 antibody which can react with GAGs in the glomerular basement membrane seems to play an important role in the pathogenesis of lupus nephritis.
Kashihara
N
N
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Hirakawa
S
S
Mino
Y
Y
Makino
H
H
Ota
Z
Z
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D006025:Glycosaminoglycans / Q000276:immunology*; D008181:Lupus Nephritis / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011094:Polyethyleneimine / Q000494:pharmacology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D006025:Glycosaminoglycans; D011094:Polyethyleneimine; D004247:DNA