The immune system in infants: Relevance to xenotransplantation

Abstract

There is a paucity of available organs for cardiac transplantation, particularly in infants and young children. Ironically, the situation is becoming more acute, as an increasing number of infants are being maintained alive by improvements in medical or surgical care. Annually, in the USA, more than 600 children with heart disease are listed for cardiac transplantation. 1 Congenital heart abnormalities are common, with an incidence of 1 in 100 live birth. 2 Despite improvements in cardiac surgery and therapeutic cardiac catheterization techniques, heart allotransplantation in patients with conditions such as hypoplastic left heart syndrome remains a curative therapy. 3-5 Some survivors of palliative surgery in infancy subsequently develop cardiac failure and ultimately require a cardiac

The potential of genetically engineered pig heart transplantation in infants with complex congenital heart disease

“…Cytotoxicity to TKO RBCs is not significantly different from that to human blood type O RBCs. Reproduced with permission from Bikhet et al 73 …”

“…Bridging with a genetically engineered pig cardiac xenograft in a neonate would have several advantages, the most important of which is the immature immune system in neonates and infants that might result in a reduced immune response to the xenograft 73 . Important aspects of this are the absence of anti‐carbohydrate antibodies, a weaker complement system, and diminished innate immune cell activity as compared to adults 73 . In contrast to adults, West et al demonstrated that ABO‐incompatible heart allotransplantation could be achieved in infants when preformed antibodies against AB carbohydrate antigens were eliminated pre‐transplantation 28 .…”

Current Aspects of Xenotransplantation in Human

“…Moreover, there is a considerable public health concern on the possible transmission and activation of PERV over the recent years [2,24]. Nowadays, a number of countries such as the USA and the UK already have guidelines for clinical trials with xenotransplantation, while some countries are still far behind [3,48,49]. This also raises concern that countries might take advantage of attracting desperate patients who need transplantation by creating xenotransplantation programs [7,30,47].…”

Scientific and psychosocial ethical considerations for initial clinical trials of kidney xenotransplantation

“…For example, infants with complex congenital heart disease may specially benefit from cardiac XTx because of (i) the poor results associated with mechanical cardiac support devices in this age group 10 and (ii) their immature immune system that may reduce the risk of xenograft rejection. 11,12 Similar to the Nuffield Council, the American Medical Association (AMA) Code of Ethics states:…”

“…Excluding children from the initial clinical trials of XTx—specifically for heart XTx in infants with complex congenital heart disease—may not be justified because they may uniquely benefit from this novel technology. For example, infants with complex congenital heart disease may specially benefit from cardiac XTx because of (i) the poor results associated with mechanical cardiac support devices in this age group 10 and (ii) their immature immune system that may reduce the risk of xenograft rejection 11,12 …”