Antigen restriction and IgG subclasses among anti-GBM autoantibodies

Thirty-seven sera positive for anti-GBM antibodies (antibodies against 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 IgG1 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.