High diversity of non-human leukocyte antigens in transplant-associated coronary artery disease1

BACKGROUND: Antibodies to endothelial derived non-human leukocyte antigens (HLA) have been associated with transplant (Tx)-associated coronary artery disease (CAD) after cardiac transplantation; however, few have been identified. The aim of this study was to screen a human coronary artery endothelial cell cDNA library with patient sera to establish the diversity and nature of the target antigens. METHODS: A human coronary artery endothelial cell cDNA library was screened with sera from seven long-term cardiac transplant patients with angiographically diagnosed TxCAD and sera from five healthy volunteers. RESULTS: Of the seven patients' sera, five showed reactivity, as did sera from two of the five normal subjects. Eighteen positive cDNA clones were isolated by TxCAD sera; DNA sequence analysis and DNA database searching identified all but one clone; 16 were nuclear or cytoplasmic proteins and 1 of them was the cell surface protein neuropilin 2. Five clones were targeted by normal sera. A different spectrum of reactive clones was identified by the sera of each patient where reactive clones were evident. CONCLUSIONS: A high diversity of non-HLA antigens, probably autoantigens, are involved in the pathogenesis of TxCAD.