ANTIGEN RESTRICTION AND IGG SUBCLASSES AMONG ANTI-GBM AUTOANTIBODIES

Thirty-seven sera positive for anti-GBM antibodies (antibodies aganist the 'Goodpasture antigen' = NC1-domain of collagen IV) in routine analysis were studied for antigen restriction and IgG subclasses. Four different polypeptides, the four alpha-chains (alpha-1, alpha-2, alpha-3 and alpha-4) of human collagen IV NC1, were used as coating in ELISA assays. Autoantibodies were detected with monoclonal antibodies towards human IgG subclasses. All patients had antibodies to the alpha-3 chain, and most patients reacted much more to the alpha-3 peptide than to any of the other three peptides. This shows that the NC1 domain of the alpha-3 chain of collagen IV is the major target for anti-GBM antibodies. A minor group of patients, 6 of 37, showed no antigen restriction and had only moderate titres. It remains to be studied, however, whether they have antibodies to another epitope and a different clinical picture. All four subclasses of IgG antibodies were present, but IgGl antibodies dominated. A group, consisting of females mainly, had relatively high titres of IgG4 antibodies to the NC1 domain of the alpha-3 chain of collagen IV.