Immunologic benefit of maternal donors in pediatric living donor liver transplantation

Abstract

Purpose of review Long‐term follow‐up has suggested that pediatric LDLT may have superior outcomes compared to deceased donor recipients. In this review, we describe the subset of LDLT recipients with maternal donors that have lower reported rates of rejection and improved allograft survival. Recent findings Pediatric LDLT recipients, particularly those with a primary diagnosis of biliary atresia who receive grafts from their mothers, have been reported to have lower rates of acute cellular rejection post‐transplant and graft failure. Maternal‐fetal microchimerism and the persistence of regulatory T cells may be related to improved outcomes observed in recipients with maternal donors. Further, recent studies have shown that up to 60% of pediatric LDLT recipients can undergo intentional withdrawal of immunosuppression and achieve long‐term operational tolerance. The impact of graft type on operational tolerance has not been thoroughly investigated; however, investigation of tolerant pediatric LDLT patients with maternal donors may provide key insights into the mechanisms of immune tolerance. Summary While excellent outcomes can be achieved in pediatric LDLT, there is still a measurable decrease in graft and patient survival over time post‐transplant. Recipients of maternal donor liver transplants are a subset of patients who may be advantaged toward improved outcomes by means of immune tolerance.

Maternal versus paternal living kidney transplant donation is associated with lower rejection in young pediatric recipients: A Collaborative Transplant Study report

“…In pediatric liver transplantation, recent data showing that maternal donation is associated with lower rejection rates and longer organ survival support our hypothesis that maternal microchimerism may have a beneficial effect on transplant outcome 17,20,38–40 . The relevance of microchimerism for transplant outcomes is further supported by Joo et al, where it is described that fetal‐maternal microchimerism‐positive patients (14 of 63, 22.2%) prior to kidney transplantation from HLA‐haploidentical family donors (mother, father, or even sibling) had a significantly lower risk of acute rejection than microchimerism‐negative patients 25 .…”

“…However, the impact on the mother and her mature immune system seems very different from the ones of the offspring with its In pediatric liver transplantation, recent data showing that maternal donation is associated with lower rejection rates and longer organ survival support our hypothesis that maternal microchimerism may have a beneficial effect on transplant outcome 17,20,[38][39][40] .…”

“…This is the first study that observes this chimerism is highest shortly after pregnancy and during breastfeeding [32][33][34] ). As mentioned earlier, several studies have shown that the cells involved in microchimerism can persist for decades [18][19][20] ; but so far, no study to date has quantified these cells over a whole lifetime.…”

“…Comparable results were not observed in children 5–9 years of age, which may be due to the fact that maternal microchimerism decreases over time. In children aged 1–4 years, only a few years have elapsed since pregnancy, and the frequency of maternal microchimerism is highest shortly after pregnancy and during breastfeeding 32–34 .. As mentioned earlier, several studies have shown that the cells involved in microchimerism can persist for decades 18–20 ; but so far, no study to date has quantified these cells over a whole lifetime. The difference in the risk of treated rejections in children 1–4 years of age in association to donor sex did, however, not translate into a difference in death‐censored graft survival.…”

“…The cells involved in microchimerism have been shown to persist for more than 30 years [18][19][20] , presuming an impact on the mother's or the child's immune system. Intriguingly, the fetal cells are tolerated in maternal immune system, although they are at least partly immunological "foreign," as 50% of genes from the offspring are of paternal origin.…”