Identification of alpha 3, alpha 4, and alpha 5 chains of type IV collagenas alloantigens for Alport posttransplant anti-glomerular basement membrane antibodies

Background. Alport syndrome is a hereditary disorder of basement membranes especially affecting the kidneys, ears, and eyes. Some patients who undergo renal transplantation lose their kidneys as a result of posttransplant ant i-glomerular basement membrane (anti-GEM) disease. Methods. In the present study, we analyzed serum from 21 unselected Alport patients who underwent renal transplantation. Eleven samples were from pati ents without posttransplant anti-GEM nephritis, and 10 were from patients w ith this disease. Results. Thirteen serum samples [10 alport posttransplant nephritis serum ( APTN) and three alport posttransplant serum (APT)] revealed linear binding to the GEM by indirect immunofluorescence, By using direct ELISA and immuno blotting with GEM constituents and type IV collagen NC1 domains from bovine , human, and recombinant sources, we detected anti-GBM antibodies in all Al port patients in varying titers, Five samples showed specific reactivity to the alpha 3 chain, four to the alpha 5 chain, six to both alpha 3 and alph a 5 chains, one to the alpha 3 and alpha 4 chains, and two to the alpha 3, alpha 4, and alpha 5 chains of type IV collagen. The varied spectrum of rea ctivities was present equally in nephritic and non-nephritic sera, Ten cont rol samples from non-Alport transplant patients did not exhibit specific bi nding to the GEM. Conclusions. These results suggest that the absence of alpha 3, alpha 4, an d alpha 5 chains of type TV collagen in the Alport kidney leads to alloanti bodies in all Alport patients who receive transplants, irrespective of whet her they develop nephritis or not, Although all Alport transplant patients develop this humoral response, only a select few develop anti-GEM disease, We suggest that this difference could be attributable to a genotypic effect on the ability of some individuals to launch a cell-mediated immune respon se.