Distribution of Goodpasture Antigens Within Various Human Basement Membranes

Abstract

Collagenase-digested basement-membrane preparations from human kidney glomeruli, kidney tubules, lung, choroid plexus, aorta, intestine, and placenta were analysed according to their reactivity to anti-glomerular basement membrane (anti-GBM) antibody-positive Goodpasture sera. Sodium dodecylsulphate polyacryl gel electrophoresis (SDS-PAGE), and immunoblotting were performed after antigen enrichment by passage of the collagenase digests through an anion-exchange column. Reactivity of anti-GBM antibodies with one to three monomers (24, 26 and 28 kD) and two dimers (44 and 50 kD) were demonstrated in basement membrane preparations of kidney glomeruli, kidney tubules, lung, placenta, and aorta. In basement membranes of choroid plexus reactivity with only the 28 kD monomer and the 50 kD dimer were identified. In intestinal basement membrane, reactivity was restricted to the 50 kD dimer. Analysis of the amounts of Goodpasture antigen by inhibition ELISA demonstrated that the highest concentration were in glomerular basement membrane, while the lowest were found in aortic basement membrane. The results indicate that Goodpasture antigens are common to all the basement membranes investigated. The differences in antigen concentration and in reactivity on immunoblotting may indicate different antigen amounts, a heterogeneity of collagen IV within the various basement membranes, or differences in antigen accessibility within the membranes. We conclude that the primary clinical restriction of the anti-GBM disease to lungs and kidneys is not explained by a preservation of the antigen to this basement membrane. Rather, the clinical pattern may be influenced by differences in the molecular composition of the basement membranes as well as by non-immunological mechanisms.