CARDIAC ALLOGRAFT VASCULOPATHY - ASSOCIATION WITH CELL-MEDIATED BUT NOT HUMORAL ALLOIMMUNITY TO DONOR-SPECIFIC VASCULAR ENDOTHELIUM

Background Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease responsible for the majority of late death s after cardiac transplantation. Although most consider this complicat ion a manifestation of chronic allograft rejection, it has not been es tablished whether this disease is a consequence of humoral or cell-med iated alloreactivity. Methods and Results Human aortic endothelial cel ls (HAECs) were isolated from donor aortas obtained at the time of org an acquisition for 52 cardiac allograft recipients. Serum and peripher al blood mononuclear cells were obtained from these 52 allograft recip ients at several time points during the first year after transplantati on. Lymphocyte proliferation (LP) in response to donor-specific HAECs and alloantibody binding to interferon-gamma-treated donor-specific HA ECs were performed and correlated with clinical parameters, including HLA matching, acute cellular rejection, and coronary artery disease on surveillance angiography. Ten of the 52 patients studied had angiogra phic or autopsy evidence of coronary artery disease in the first postt ransplantation year (CAV + group). The CAV+ group had higher LP respon ses to their donor HAECs at 1 week, 3 months, and 6 months after trans plantation compared with the CAV- group (1 week: 1439+/-222 versus 824 +/-141 counts per minute [cpm], P=.026; 3 months: 1282+/-388 versus 88 4+/-94 cpm, P=.07; 6 months: 2504+/-635 versus 1540+/-209 cpm, P=.036; CAV+ versus CAV-, respectively). Only 8 of the 52 patients had donor- specific alloantibodies, and there was no relation between antibody pr esence and CAV. Other clinical parameters that correlated with CAV inc luded the level of HLA-DR mismatch and the presence of late acute reje ction. Conclusions CAV is associated with donor-specific cell-mediated alloreactivity to vascular endothelium. Humoral immunity does not app ear to have a major role in this disease.