Chronic renal allograft rejection: the significance of non-MHC alloantigens

Abstract

We studied the role of polymorphic endothelial antigens other than MHC in antibody-mediated chronic renal allograft rejection in two models. In the first model, donor Lewis rat kidneys were transplanted into BN recipients that had been made tolerant for donor class I antigens at the B cell (antibody) level. In this setting Lewis kidney grafts were chronically rejected with stable renal function but increasing proteinuria (> 100 mg/24 h). Rejected graft tissue showed mononuclear cell infiltration and the presence of glomerular vasculonecrotic lesions with fibrinoid material, associated with IgG and IgM deposition, but with absent or weak C3 binding. Graft endothelium showed no expression of MHC class II antigens. Serum antibodies were not reactive with donor class I antigens, but did react with endothelial non-MHC alloantigens. In the second model, more direct information on the role of endothelial non-MHC alloantigens in renal allograft rejection was obtained by transplanting Lewis 1 N kidneys into unmodified BN recipients (MHC-matched transplants). Here, similar to the first model, the animals developed severe proteinuria with stable renal function. Histopathological examination showed mononuclear cell infiltration and deposition of IgM and IgG along the glomerular vasculature, but this time in the presence of strong C3 reactivity. However, glomerular vasculonecrotic lesions with intense fibrin deposition were not observed. The data showed that although clinically the two kidney transplantation models used gave similar chronic rejection phenomena, histopathologically some striking differences were observed in the glomeruli. The precise mechanisms effecting chronic rejection of the grafts is still a puzzle. However, immune reactivity against graft (endothelial) non-MHC antigens may play a significant role.