Analysis of immune markers in human cardiac allograft recipients and association with coronary artery vasculopathy.
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.
Poggio
Emilio D
ED
Department of Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Roddy
Meagan
M
Riley
Jocelyn
J
Clemente
Michael
M
Hricik
Donald E
DE
Starling
Randall
R
Young
James B
JB
Gus
Barbara
B
Yamani
Mohamad H
MH
Heeger
Peter S
PS
D000917:Antibody Formation / Q000276:immunology; D015415:Biomarkers / Q000032:analysis*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis*; D007518:Isoantibodies / Q000032:analysis; D008297:Male; D008875:Middle Aged; D014180:Transplantation
D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies; D007371:Interferon-gamma