Analysis of immune markers in human cardiac allograft recipients and association with coronary artery vasculopathy

Abstract

Background: 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.

Methods: 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)-gamma 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.

Results: 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.

Conclusions: 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.