Cardiac allograft vasculopathy: relationship with acute cellular rejection and histocompatibility

Abstract

This article reviews the literature and summarizes the data obtained at Loyola University of Chicago about the relationship between rejection, histocompatibility, and cardiac allograft vasculopathy. Both the studies concerning the relationship between rejection and cardiac allograft vasculopathy and those evaluating the impact of histocompatibility on cardiac allograft vasculopathy have produced conflicting results. Most studies are retrospective and include a small number of patients followed up for short periods of time and treated with variable immunosuppressive regimens. In addition, the diagnosis of cardiac allograft vasculopathy is based on angiographic detection of coronary arterial abnormalities, a method that is known to underestimate the presence and severity of cardiac allograft vasculopathy. The ability to assess the impact of histocompatibility on the development of cardiac allograft vasculopathy is also limited by the lack of uniformity in the type and number of HLA variables analyzed, the extreme polymorphism of the HLA antigens and variability in serologic tissue typing techniques and quality. The results of our study suggest that complete mismatch at the HLA-B and -DR loci is associated with higher rejection rates and severity and with increased mortality. We also noted a trend toward a higher incidence of cardiac allograft vasculopathy in patients with complete mismatch at the HLA-DR locus. Future experimental and clinical studies should be done with use of molecular tissue typing techniques to further elucidate the impact of histocompatibility on cardiac allograft vasculopathy. The role of non-HLA antigens in the development of cardiac allograft vasculopathy requires further definition. Because in heart transplantation the short donor ischemic times compatible with a successful outcome limit the feasibility of prospective donor/recipient tissue typing, the development of immunosuppressive drugs that effectively reduce the detrimental effects of tissue incompatibility is crucially needed.