Chronic renal allograft rejection. Selective involvement of the glomerular endothelium in humoral immune reactivity and intravascular coagulation.
To study immune reactive and thrombotic mechanisms involved in chronic renal allograft rejection, Lewis rat kidneys were transplanted into bilaterally nephrectomized Brown Norway recipients tolerant of LEW erythrocyte antigens. Such BN rats fail to produce anti class I MHC alloantibodies after insertion of a LEW kidney. The LEW renal allografts experience a transient rejection episode without proteinuria followed by the development of chronic rejection, clinically characterized by glomerular proteinuria in the presence of stable renal function. Immunohistological studies of such chronically rejected LEW renal allografts showed the occurrence of glomerular and interstitial infiltration of predominantly monocytes and T cells. CD4-positive T cells dominated over CD8-positive T cells in the chronically rejected LEW renal grafts. IgG deposition was found deposited throughout the renal vasculature--this in contrast to IgM, which was observed only in the glomerular vasculature. Glomerular antibodies were not directed to endothelial class II MHC antigens, and showed only weak complement fixation as demonstrated by C3 staining. Selective glomerular IgM deposition was associated with vascular (platelet-containing) thrombi, and focal and segmental fibrinoid necrosis. In contrast, acutely rejected LEW renal grafts in unmodified BN recipients showed IgM deposition as well as thrombus formation throughout the entire renal vasculature. The results demonstrate that the antibody response to endothelial--and, in particular, glomerular endothelial non-MHC antigens--may bring about chronic vascular renal allograft rejection. How the formation of glomerular thrombotic lesions may be assisted by endothelial reactivity to cytokines from local immune reactive cells is discussed.
Duijvestijn
A M
AM
Department of Immunology, University of Limburg, Maastricht, The Netherlands.
van Breda Vriesman
P J
PJ
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001777:Blood Coagulation; D004727:Endothelium / Q000166:cytology / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013927:Thrombosis / Q000209:etiology