Microchimerism after heart transplantation: prevalence, predisposing factors, natural history, and prognosis

Abstract

THE SUCCESS of heart transplantation (HT) is still marred by the need for chronic immunosuppression using agents that display not only limited efficacy and specificity but also considerable toxicity. Overall 1-year survival is only 81%, and patient half-life (the time at which the survival rate has dropped to 50%) is 9.8 years. The induction of tolerance to transplanted organs, might make transplantation safer as well as more successful. Certain studies of recipients of solid organs, including liver, kidney, lung, and heart seem to be associated with apparent induction of tolerance and with the persistence of low levels of donor cells of bone marrow origin (microchimerism). Other studies, however, have not found an association between microchimerism and tolerance, and there have also been cases of apparently tolerant recipients who do not show detectable microchimerism. These discrepancies may be explained by differences in the prevalence of microchimerism depending on the organ type and the time after transplantation. Despite these controversies, some workers have attempt to increase the possibility of tolerance by induction enhancing microchimerism via donor bone marrow infusion (DBMI) at the time of transplantation. The work described herein includes studies of the prevalence and natural history of microchimerism after HT, as well as predisposing factors to establish the state, and its relevance to the outcomes of survival, rejection and steroid requirements.