CHRONIC RENAL-ALLOGRAFT REJECTION IN THE RAT - TRANSPLANTATION-INDUCED ANTIBODIES AGAINST BASEMENT-MEMBRANE ANTIGENS

BACKGROUND: To obtain understanding of the immunologic mechanism of ch ronic rejection-associated glomerular and interstitial renal damage, w e investigated the humoral immune response against donor type glomerul ar and tubular basement membrane proteins in rats with long-surviving renal transplants with and without chronic rejection. EXPERIMENTAL DES IGN: Sera from Lewis and Fisher 344 rats with long-surviving Fisher 34 4 and Lewis renal allografts were investigated by enzyme-linked immuno sorbent assay and Western blot analysis using collagenase-digested ren al basement membrane preparations from various strains of rats. RESULT S: Kidneys from F344 strain donors transplanted into Lewis recipients developed glomerular lesions consistent with transplant glomerulopathy as well as chronic tubulointerstitial inflammation and fibrosis. Indi rect immunofluorescence studies of the Lewis anti-Fisher 344 posttrans plant sera showed the presence of antibodies that gave punctate staini ng in the glomeruli and bright, linear staining of the proximal tubula r basement membrane. Dot blot analysis of the sera showed the presence of antibodies against Fisher and third party Brown Norway glomerular basement membranes, whereas no reactivity was found with recipient str ain basement membranes. Western blot analysis with glomerular basement membrane preparations showed that the antibodies recognized several a ntigens under nonreducing (>200 and similar to 100 kilodaltons) and re ducing (greater than or equal to 200, similar to 200, similar to 90, s imilar to 50 to 60, and <45 kilodaltons) conditions. Western blots wit h tubular basement membrane proteins showed antibodies against various antigens. Anti-basement membrane antibodies were not found after conv entional immunizations with kidney homogenates or after transplantatio n of cardiac allografts. Fisher 344 rats with long-surviving Lewis ren al transplants produced antibodies against laminin fragments, but thes e antibodies were not associated with transplant glomerulopathy. CONCL USIONS: We found that Lewis rats that carry a Fisher 344 renal allogra ft with transplant glomerulopathy produce antibodies against one or mo re novel antigen(s) of donor glomerular and tubular basement membranes . The role of these antibodies in the pathogenesis of transplant glome rulopathy and chronic rejection-associated tubulointerstitial inflamma tion remains to be established.