MECHANISMS OF CORNEAL ALLOGRAFT REJECTION

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This project will examine several genetic and immunologic parameters in human corneal transplant recipients to explore possible correlations with allograft rejection. Specifically, patients at high risk for rejection because of corneal vascularization or prior graft loss will receive only ABO blood group, donor-lymphocyte crossmatch negative grafts with the benefit of prospective HLA-A,-B,-C and -DR matching evaluated. Both high- and low-risk patients will be screened prior to grafting for the persence of antibodies to histocompatibility antigens, lymphocyte differentiation markers, vascular endothelium antigens, and corneal tissue antigens. Similar evaluation will be performed post-transplant and during rejection episodes. Donor-specific reactivity will be assessed by utilizing an annulus of donor cornea for indirect immunofluorescence with recipient serum. Detection and characterization of antibodies will be made using both sensitive microcytotoxicity and antigen binding assays to determine whether certain functional characteristics may correlate with rejection. Host cellular immunity will also be examined using lymphocyte mediated cytotoxicity against human lymphocytes, corneal cells and vascular endothelium. Both fresh and cultured human corneal endothelial cells will be examined for the expression of various antigens using a variety of serologic assays. Monoclonal, as well as isologous and heterologous serum reagents with specificity for HLA antigens, lymphocyte differentiation antigens, and vascular endothelium/monocyte antigens, will be used to characterize such corneal endothelial markers. These studies are proposed to: 1) determine if prospective HLA-A,-B,-C and -DR donor-recipient matching is of benefit in crossmatch negative high-risk corneal allograft patients; 2) determine if any detectable serologic or cellular parameter of immunity is of diagnostic or prognostic value in predicting eventual graft rejection; 3) determine the antigenic nature of the corneal endothelium which is an important target for immune mediated graft rejection.