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

W. Page Faulk, Marlene Rose, Pier L. Meroni, Nicoletta Del Papa, Ronald J. Torry, Carlos A. Labarrere, Karen Busing, Samantha J. Crisp, Michael J. Dunn, David R. Nelson

Research output: Contribution to journalArticle

Abstract

Background. Transplant-induced coronary artery disease is a leading cause of graft failure in cardiac allograft recipients after the first year of transplantation, but there presently is no test to identify patients at high risk for developing the disease. Our research is focused on development of a predictive test to identify patients at high risk of developing the disease. Methods. Sixty-eight cardiac allograft recipients transplanted, and followed at Methodist Hospital between 1982 and 1996 were studied. Serial annual angiograms were used to diagnose coronary artery disease, and serial endomyocardial biopsies were used to detect cellular infiltrates and microvascular disease. Biopsy-matched serum samples were used for cardiac troponin-T determinations as measures of myocardial damage, and serum antibodies to endothelial cells were determined by using flow cytometry, enzyme-linked immunosorbent assay and immunoblotting techniques. The endothelial antibody data were evaluated statistically for associations with angiographic changes, biopsy findings and biochemical evidence of myocardial damage. Findings. Antibodies to endothelial cells were identified by all three techniques, and significant associations were found for the amount of antibody identified by Western immunoblotting with histological rejection grades in biopsies, which were confirmed immunocytochemically as macrophages (p <0.01) and T lymphocytes (p = 0.03). These antibodies also associated significantly with vascular antithrombin depletion (p = 0.02), biochemical evidence of myocardial damage (p = 0.005) and subsequent development of coronary artery disease (p = 0.03). Interpretation. The significant association of anti-endothelial antibodies with cellular infiltrates, depletion of vascular antithrombin and myocardial damage suggests a role for antibody in the development of transplant-induced arteriopathy. The significant association of anti-endothelial antibodies with the future development of coronary artery disease further suggests that assessment of these antibodies may provide a non-invasive test to predict the development of transplant-induced coronary artery disease.

Original languageEnglish
Pages (from-to)826-832
Number of pages7
JournalHuman Immunology
Volume60
Issue number9
DOIs
Publication statusPublished - Sep 1999

Keywords

  • Anti-endothelial antibodies
  • Cardiac allografts
  • Immunocytochemistry
  • Western immunoblotting

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Faulk, W. P., Rose, M., Meroni, P. L., Del Papa, N., Torry, R. J., Labarrere, C. A., Busing, K., Crisp, S. J., Dunn, M. J., & Nelson, D. R. (1999). Antibodies to endothelial cells identify myocardial damage and predict development of coronary artery disease in patients with transplanted hearts. Human Immunology, 60(9), 826-832. https://doi.org/10.1016/S0198-8859(99)00056-7