Antigen restriction and IgG subclasses among anti-GBM autoantibodies

Thirty-seven sera positive for anti-GBM antibodies (antibodies against the ‘Goodpasture antigen’ = NCI-domain of collagen IV) in routine analysis were studied for antigen restriction and IgG subclasses. Four different polypeptides, the four α-chains (α₁, α₂, α₃ and α₄) of human collagen IV NCI, were used as coating in ELISA assays. Autoantibodies were detected with monoclonal antibodies towards human IgG subclasses. All patients had antibodies to the α3 chain, and most patients reacted much more to the α3 peptide than to any of the other three peptides. This shows that the NCI domain of the α3 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 NCI domain of the α3 chain of collagen IV.