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

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. 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. 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. A high diversity of non-HLA antigens, probably autoantigens, are involved in the pathogenesis of TxCAD.