Role of antibodies in transplant-associated cardiac allograft vasculopathy.

Transplant-associated coronary artery disease or cardiac allograft vasculopathy is the major complication after cardiac transplantation. Here we discuss the role of antibodies and antibody-mediated activation of endothelial cells in the pathogenesis of this disease. Clinical and experimental studies have both described an association between chronic production of antibodies after transplantation and development of TxCAD. Although anti-HLA antibodies have been described in some cases, our studies suggest that antibodies against endothelial cells, for example, vimentin, are closely associated with disease development. It is known that indirect presentation of antigens, derived from the graft, probably drive chronic rejection. Here we are suggesting that minor antigens, released from damaged parenchymal cells within the graft, are responsible for the chronicity of the antibody response after transplantation. To date, only vimentin has been identified, but there may be a multiplicity of antigens. It is known that antibodies against endothelial cell surface molecules such as MHC class I and ICAM-1 can activate vascular cells (endothelial and smooth muscle cells) leading to exacerbation of the inflammatory response within the vessel wall. It remains to be seen whether antibodies against cytolytic proteins, released as a result of cell damage, cause cell activation; it may be that these antibodies are involved in clearance of apoptopic cells released from the graft.