Protective antibodies in successful renal transplantation and normal pregnancy
Immunological rejection remains the commonest cause of renal transplant failure. Two approaches to this problem are discussed in this Thesis. Firstly, since certain non-cytotoxic antibodies linked to the major histocompatibility complex (MHC) in the animal model were found to have a beneficial effect on renal transplant outcome, a similar role was sought for them in clinical renal transplantation. Their presence was also determined in association with normal pregnancy as the semi-allogeneic foetus may be considered a successful transplant. Secondly the effect of matching donor and recipient pairs at the recently defined HLA-DR locus on renal transplant survival was assessed. Antibody activity was principally assessed using the Erythrocyte Antibody Rosette Inhibition (EAI) Assay which detects the presence of noncytotoxic Fc-receptor blocking antibodies. The results show that: 1) EA inhibiting antibodies occurring prior to transplantation are associated with improved human renal transplant survival; 2) Such antibodies developed following blood transfusion; 3) EA inhibiting antibodies occurred in association with normal pregnancy but not in women subject to spontaneous abortion; 4) Antibodies detected by the EA inhibition assay showed a restricted distribution pattern when tested against lymphocyte panels but appeared not to be directed towards HLA-A, B or DR antigens; 5) These antibodies were linked to the Major Histocompatibility Complex (MHC) (determined by family studies); 6) HLA-DR matching improved renal allograft survival. It is suggested therefore that Fc-receptor blocking antibodies detected by the EA Inhibition assay may be directed against an as yet undefined HLA-linked antigen system and may have a protective role in successful renal transplantation and normal pregnancy. Since they occur following blood transfusion, EA inhibiting antibodies may provide a possible explanation for the beneficial effect of blood transfusions on renal transplant survival, and their presence in recipient serum prior to transplantation might be used as one of the criteria for cadaver donor renal transplant recipient selection.