Antibodies to endothelial cells identify myocardial damage and predict development of coronary artery disease in patients with transplanted hearts

Background. Transplant-induced coronary artery disease is a leading cause o f graft failure in cardiac allograft recipients after the first year of tra nsplantation, but there presently is no test to identify patients at high r isk for developing the disease. Our research is focused on development of a predictive test to identify patients at high risk of developing the diseas e. Methods. Sixty-eight cardiac allograft recipients transplanted and followed at Methodist Hospital between 1982 and 1996 were studied. Serial annual an giograms were used to diagnose coronary artery disease, and serial endomyoc ardial biopsies were used to detect cellular infiltrates and microvascular disease. Biopsy-matched serum samples were used for cardiac troponin-T dete rminations as measures of myocardial damage, and serum antibodies to endoth elial cells were determined by using flow cytometry, enzyme-linked immunoso rbent assay and immunoblotting techniques. The endothelial antibody data we re evaluated statistically for associations with angiographic changes, biop sy findings and biochemical evidence of myocardial damage. Findings. Antibodies to endothelial cells were identified by all three tech niques, and significant associations were found for the amount of antibody identified by Western immunoblotting with histological rejection grades in biopsies, which mere confirmed immunocytochemically as macrophages (p < 0.0 1) and T lymphocytes (p = 0.03). These antibodies also associated significa ntly with vascular antithrombin depletion (p = 0.02), biochemical evidence of myocardial damage (p = 0.005) and subsequent development of coronary art ery disease (p = 0.03), Interpretation, The significant association of anti-endothelial antibodies with cellular infiltrates, depletion of vascular antithrombin and myocardia l damage suggests a role for antibody in the development of transplant-indu ced arteriopathy. The significant association of antiendothelial antibodies with the future development of coronary artery disease further suggests th at assessment of these antibodies may provide a non-invasive test to predic t the development of transplant-induced coronary artery disease. (C) Americ an Society for Histocompatibility and Immunogenetics, 1999. Published by El sevier Science Inc.