CHARACTERIZATION OF ANTI-GBM ANTIBODIES INVOLVED IN GOODPASTURES-SYNDROME

Goodpasture's syndrome is a life threatening autoimmune kidney disease . The patients have autoantibodies to the glomerular basement membrane , which are specific for the C-terminal domain of type IV collagen (NC 1). The major antigen has been localized to the alpha 3(IV)-chain. We have investigated sera from 44 patients with anti-NC1 antibodies. The quantity of antibodies to four different alpha(IV)-chains of type IV c ollagen was measured with direct ELISA. We used affinity chromatograph y to separate the antibodies and their specificities were studied with ELISA. The results show that about 1% of the patients total IgG are a nti-NC1 antibodies and that 90% of these antibodies are specific for t he alpha 3(IV)-chain. Antibodies to the other alpha(IV)-chains were fo und in 80% of the patients. Furthermore, affinity purified anti-alpha 3(IV) antibodies from one patient were inhibited by antibodies from th e other patients, from 4 to 72%. The antibodies, from 39 of the patien ts, were inhibited by a monoclonal antibody against the alpha 3(IV)-ch ain. The results indicate that patients with Goodpasture's syndrome ca n have antibodies to most of the alpha(IV)-chains, while the majority of anti-NC1 antibodies are restricted to the alpha 3(IV)-chain. Moreov er the number of epitopes seems to be limited and the majority of the antibodies from most patients are against one single epitope on the al pha 3(IV)-chain.