Chronic renal allograft rejection in the rat. Transplantation-induced antibodies against basement membrane antigens.
BACKGROUND
To obtain understanding of the immunologic mechanism of chronic rejection-associated glomerular and interstitial renal damage, we investigated the humoral immune response against donor type glomerular and tubular basement membrane proteins in rats with long-surviving renal transplants with and without chronic rejection.


METHODS
Sera from Lewis and Fisher 344 rats with long-surviving Fisher 344 and Lewis renal allografts were investigated by enzyme-linked immunosorbent assay and Western blot analysis using collagenase-digested renal basement membrane preparations from various strains of rats.


RESULTS
Kidneys from F344 strain donors transplanted into Lewis recipients developed glomerular lesions consistent with transplant glomerulopathy as well as chronic tubulointerstitial inflammation and fibrosis. Indirect immunofluorescence studies of the Lewis anti-Fisher 344 post-transplant sera showed the presence of antibodies that gave punctate staining in the glomeruli and bright, linear staining of the proximal tubular 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 strain basement membranes. Western blot analysis with glomerular basement membrane preparations showed that the antibodies recognized several antigens under nonreducing (> 200 and approximately 100 kilodaltons) and reducing (> or = 200, approximately 200, approximately 90, approximately 50 to 60, and < 45 kilodaltons) conditions. Western blots with tubular basement membrane proteins showed antibodies against various antigens. Anti-basement membrane antibodies were not found after conventional immunizations with kidney homogenates or after transplantation of cardiac allografts. Fisher 344 rats with long-surviving Lewis renal transplants produced antibodies against laminin fragments, but these antibodies were not associated with transplant glomerulopathy.


CONCLUSIONS
We found that Lewis rats that carry a Fisher 344 renal allograft with transplant glomerulopathy produce antibodies against one or more novel antigen(s) of donor glomerular and tubular basement membranes. The role of these antibodies in the pathogenesis of transplant glomerulopathy and chronic rejection-associated tubulointerstitial inflammation remains to be established.
de Heer
E
E
Department of Pathology, University of Leiden, The Netherlands.
Davidoff
A
A
van der Wal
A
A
van Geest
M
M
Paul
L C
LC
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology*; D015153:Blotting, Western; D006084:Graft Rejection; D007678:Kidney Glomerulus / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors
D000941:Antigens