ABO-incompatible heart transplantation: an alternative to improve the donor shortage in infants

Purpose of review This paper reviews recent trends that have allowed crossing the ABO blood group barrier in organ transplantation and, in particular, the unique situation of cardiac transplantation in infancy. Recent findings The ABO barrier in organ transplantation was previously considered insurmountable, but severe donor shortages continue to prompt attempts to breach it. Recent developments in strategies to remove preformed antibodies and eliminate B lymphocytes have allowed significant progress in ABO-incompatible renal and hepatic transplantation. Cardiac transplantation continues to be excluded from this trend due to lack of effective rescue therapies and the likelihood of lethal outcome of anti body-mediated rejection. In infants, however, developmental immaturity allows ABO-incompatible cardiac transplantation to be under-taken safely without aggressive immunologic interventions. This contributes to a significant broadening of the potential donor pool for infants, maximizing the likelihood of transplantation and minimizing wastage of donor organs. In contrast to older organ transplant recipients, whose grafts may undergo 'accommodation' following ABO-incompatible transplantation, infant recipients develop donor-specific B-cell tolerance to graft ABO antigens. Summary ABO-incompatible cardiac transplantation has been demonstrated to be safe in infants and results in lower waiting list mortality. The immaturity of the infant immune system can be exploited to great advantage in this setting. The demonstration that neonatal immune tolerance develops in human infants after transplantation, previously shown only in murine models, has profound significance for research in tolerance.