Analysis of Immune Markers in Human Cardiac Allograft Recipients and Association With Coronary Artery Vasculopathy

• Published in: The Journal of heart and lung transplantation Vol. 24; no. 10; pp. 1606 - 1613
• Main Authors: Poggio, Emilio D., Roddy, Meagan, Riley, Jocelyn, Clemente, Michael, Hricik, Donald E., Starling, Randall, Young, James B., Gus, Barbara, Yamani, Mohamad H., Heeger, Peter S.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2005; Elsevier Science
• Subjects: Antibody Formation - immunology; Biological and medical sciences; Biomarkers - analysis; Coronary Angiography; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - immunology; Cross-Sectional Studies; Female; Heart Transplantation - adverse effects; HLA Antigens - analysis; Humans; Immunity, Cellular - immunology; Interferon-gamma - analysis; Isoantibodies - analysis; Male; Medical sciences; Middle Aged; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Transplantation; Heart; Human; Respiratory disease; Coronary artery; Biological marker; Cardiovascular disease; Transplantation; Homotransplantation; Vascular disease; Association; Treatment; Analysis; Surgery; Graft
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2004.12.110

Because coronary artery vasculopathy (CAV) is a common cause of late cardiac allograft loss in humans, there is a need to develop and test non-invasive surrogate markers capable of detecting and predicting this disease entity. We performed a cross-sectional analysis of immune-based surrogate markers in 65 primary cardiac allograft recipients with or without angiographically documented CAV. Anti-donor cellular immunity was determined by interferon gamma (IFN)-γ enzyme-linked immunosorbent spot (ELISPOT) assays using donor HLA–derived peptides (indirect pathway), and anti-donor alloantibodies were detected by flow cytometry using HLA-coated beads. Anti-donor cellular and humoral immunity were detected more frequently in patients with CAV (17 of 32, 53.1%) than in controls (4 of 33, 12.1%) ( p < 0.001). Anti-donor cellular and humoral immunity were detected in different sub-groups of CAV patients; peripheral blood lymphocytes (PBLs) from only 1 of 32 CAV patients reacted to donor peptides with simultaneous detection of peripheral anti-donor alloantibodies. Immune reactivity in cardiac transplant recipients with CAV differs significantly from those without CAV and the detected responses are heterogeneous in nature. Serial assessments of anti-donor immunity using different methods will be required to detect and possibly predict outcome in cardiac transplant recipients.