Clinical relevance of feto-maternal microchimerism in (hematopoietic stem cell) transplantation

Abstract

Toleration of a semi-allogeneic fetus in the mother’s uterus as well as tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) appear to share some immunologic concepts. The existence of microchimeric cells, and the original idea of a bidirectional cell trafficking between mother and child during pregnancy have been known for decades. Today, origins and mechanisms of persistence of microchimeric cells are intensively being elucidated. Both, the translation of the phenomenon of feto-maternal immune tolerance to donor choice or prevention of graft-versus-host disease (GvHD) in HSCT, and the implications of microchimeric cells in and for HSCT are highly intriguing. Yet, differences in detection methods of microchimeric cells, as well as in transplantation protocols impede the comparison of larger cohorts, and limit potential clinical advice. Still, matching of non-inherited maternal antigens (NIMA), which are expressed on maternal microchimeric cells, demonstrated a strong association with decreased risk for the development of acute GvHD in the context of various transplantation strategies. Despite the fact that advances in graft manipulation and immunosuppression ameliorated the safety and outcome after HSCT, NIMA-matching retained a beneficial role in selection of sibling, child, or maternal donors, as well as for cord blood units. Recent findings indicate the existence of a microchimeric stem cell niche, in which only one dominant microchimeric cell population of only one semi-allogeneic origin persists at a time. This implies that studies regarding the impact of (maternal and fetal) microchimerism (MC) on clinical outcome of HSCT should combine analysis of NIMA and direct detection of microchimeric cells from donor and recipient on the verge of HSCT to be efficiently conclusive.