CHARACTERIZATION OF A NON-GOODPASTURE AUTOANTIBODY TO TYPE-IV COLLAGEN

Goodpasture's syndrome is a very severe and aggressive autoimmune kidn ey disease. The patients' autoantibodies, which are pathogenic, are re stricted to the C-terminal region of the alpha3-chain of type IV colla gen. In this paper we characterize an antitype IV collagen antibody fr om a patient with a non-progressive form of glomerulonephritis. ELISA and immunoblotting were used to study the specificity of this patient' s antibodies. The patient had high titres of antibodies restricted to the C-terminal region of the alpha1-chain of type IV collagen. The ant ibody recognized an epitope hidden in the NC1 molecule which was fully exposed after denaturation or reduction. It was an IgG3 antibody comp osed of only lambda light chains, indicating that it has a potential t o induce inflammatory damage and that it is probably monoclonal. This patient also had MPO-ANCA which were of IgG1 subclass. Our patient had no disease progression during the 5 years of treatment. Even though t he anti-alpha1(IV) antibodies react with the same domain, but of a dif ferent chain of type IV collagen compared to the Goodpasture's antibod ies, they do not induce any severe damage. It is thus uncertain if the anti-alpha1 (IV) antibodies have any pathogenic role; the kidney dama ge might have been caused by the MPO-ANCA. The findings support the th eory that the anti-alpha3(IV) antibody causes disease in Goodpasture's syndrome and that antibodies restricted to other subunits of the C-te rminal region of type IV collagen are less harmful.