Advancing the Science of Transplantation: Lessons Learned from Children
The role of the clinician-scientist has been of crucial importance in advancing the field of organ transplantation, in which an artificial disease state' is created by the surgical placement of a donor organ into a recipient. A unique immunologic situation is formed between the host immune system and the specific antigens of the graft. Over half a century ago, clinician-scientists Ray Owen, Peter Medawar, Rupert Billingham and Leslie Brent discovered in animal models that immaturity has distinct advantages in transplant immunobiology. Thus, the normal developmental immune deficiencies, such as lack of immunologic memory, that render neonates susceptible to overwhelming infection may be exploited to the advantage of infants needing organ transplants. Heart transplantation, in particular, is performed in the very youngest patients, often after fetal imaging reveals complex congenital cardiac malformations. By applying rigourous scientific enquiry to this patient population and by encouraging clinical practice to evolve in ways that are specifically applicable to their developmental status, infancy emerges as arguably the most favourable time for transplantation to be undertaken. Compared to outcomes of transplantation performed at any later time, the advantages of infant transplantation continue to be observed into early adulthood. Clearly major challenges remain in identifying sufficient donors and in generating adequate scientific understanding of immune events to allow lightening of the clinical burden of immunosuppression. Although early transplant clinicians and scientists would not have foreseen that infant heart transplantation would one day be successful or even feasible, their insights set the steps for this evolution to occur.
- © 2010 by American Heart Association, Inc.