Characterization of the human Goodpasture antigen

The glomerular basement membrane antigen involved in Goodpasture syndrome was purified from human kidneys. The antigen was solubilized by collagenase digestion and purified by ion exchange chromatography, gel filtration and reversed phase HPLC. The monomer proteins (M1, M2*, and M3) were immunochemically compared with the corresponding bovine monomers and appeared to be identical. The Goodpasture reactivity was localized to the same monomer (M2*) as in bovine material. It could also be shown that eight out of nine patients with Goodpasture syndrome had circulating antibodies reacting with a crude collagenase digest of human glomerular basement membrane that could be inhibited by the active monomer peptide. The ninth patient had, besides antibodies to this peptide, antibodies to the 7S domain of type IV collagen. Further immunochemical studies indicate that all patients sera recognize the same site(s) on the monomer protein. Thus the major antigenic determinant(s) of Goodpasture syndrome resides in monomer M2* which is a constituent of the globular domain of collagen IV.