Age and the immune response in pediatric renal transplantation

Abstract

Because renal transplant outcome is poorer in young children when compared with older children or adults, it is reasonable to question whether immune reactivity relative to renal allograft rejection differs between young children and adults. While this hypothesis is far from established, preliminary data suggest that young children may represent an immunologically-defined subgroup distinct from adults and perhaps at high risk for renal allograft rejection. From a histocompatibility standpoint, infants may show some subtle differences in HLA typing results when compared with older children or adults. Children may also be at higher risk than adults for rejection when the transplant is performed in the presence of a historically positive, currently-negative lymphocytotoxicity crossmatch. Several non-specific tests of cellular immunity have been used to characterize the strong immunologic responder, i.e. the person who has an increase tendency to vigorously reject a renal allograft. Children in general and young children in particular may fall into this group. Children 5 years old and younger have significantly increased numbers of CD2+, CD3+, and CD4+ T lymphocytes when compared with older children. Young children also have higher than expected functional indices of cellular immune function. Taken together, these data suggest that children, and particularly young children, may have a heightened immunologic responsiveness, which may in turn represent an increased propensity for allograft rejection. Appropriate modification in immunosuppression may be indicated to optimize renal transplant outcome.

Circulating donor-specific cytotoxic T lymphocytes with high avidity for donor human leukocyte antigens in pediatric and adult cardiac allograft valved conduit recipients✩

“…However, a recent study regarding pediatric renal transplantation demonstrated more rejection episodes and a greater irreversibility of rejection in younger recipients, supporting the hypothesis of an increased immune responsiveness [22]. Ettenger proposed higher functional indices of immune competent cells in children less than 5 years old as a cause for higher immune reactivity [23]. In our study, we have demonstrated a comparable increase in both the number of circulating CTLp and its high-avidity fraction within pediatric and adult patients.…”

Management of the pediatric liver transplant patient

“…29,30 A calcineurin inhibitor, either cyclosporine or tacrolimus, forms the basis of most induction protocols, along with a variable course of intravenous steroids that begins at a high dose and is rapidly tapered to a relatively low dose of 0.3 to 0.5 mg/kg/d, usually by the end of the first week. Whether tacrolimus-compared with cyclosporine-based primary therapy has important advantages is still a matter of controversy.…”

Corticosteroid avoidance in pediatric renal transplantation

“…Younger children have a greater number of immunocompetent functional immune cells compared to their adult counterparts, which may result in relatively heightened early post-transplant immune responsiveness. Continued growth of pediatric patients requires frequent monitoring and dose adjustments, resulting in more potent and complex immunosuppressive regimens in pediatric transplant patients when compared to adults [4,5,6]. Nevertheless, once beyond the first post-transplant year, pediatric patients receiving adultsized, well-functioning organs have excellent long term outcomes, on par with (or even better than) adult recipients [2,3,7,8].…”

“…The dose of prednisone required to achieve optimal immunosuppression is unknown, and dosing and subsequent tapering of steroid doses is performed empirically [4,11].…”