PEPTIDE INHIBITION OF GLOMERULAR DEPOSITION OF AN ANTI-DNA ANTIBODY

Antibodies to double-stranded DNA are pathognomonic of systemic lupus erythematosus and deposit in the kidneys of lupus patients to cause gl omerulonephritis. Recent data suggest that a significant proportion of anti-DNA antibodies may cross-react with renal antigens and be seques tered in the kidney by virtue of this cross-reactivity, If this is tru e, antigenic competition for pathogenic antibodies might prevent their deposition in kidneys and the ensuing tissue damage, To generate surr ogate antigens that could be used for this purpose, we have used pepti de display phage libraries to identify peptides that react with R4A, a pathogenic mouse monoclonal anti-DNA antibody that deposits in glomer uli, We have demonstrated that the peptides bind in or near the double -stranded DNA binding site, Furthermore, the peptides are bound prefer entially by the R4A antibody as compared with two closely related anti bodies derived from it, one of which deposits in renal tubules and one of which displays no renal pathogenicity, Administration of one of th ese peptides in a soluble form protects mice from renal deposition of the R4A anti-DNA antibody in vivo, This represents a new therapeutic a pproach in systemic lupus erythematosus that focuses on protecting tar get organs from antibody mediated injury.