A feasibility study on the prediction of acute graft-vs.-host disease before hematopoietic stem cell transplantation based on fetomaternal tolerance

Abstract

The contact between the immune systems of mother and child during pregnancy affects an immune response of the child against noninherited maternal antigens (NIMA) and the mother against inherited paternal antigens (IPA). However, the immunologic effects of developmental exposure to NIMA or IPA are heterogeneous, and can be either tolerogenic or immunogenic. Although we have reported that prediction of acute graft-vs.-host disease (GVHD) is feasible in a murine model, there has been no literature in human. We devised a novel method for predicting a tolerogenic effect by using mixed lymphocyte reaction combined with enzyme-linked immunospot (MLR-ELISPOT) assay. The assay can evaluate reactivity of interferon-γ spot-forming cells of donor against the recipient. Although we have shown only two examples of mother to child reactivity so far, our preliminary results suggest that this pre-screened assay may be used to predict acute GVHD. The clinical trial is in progress to evaluate MLR-ELISPOT assay as a predicting measure of acute GVHD in haploidentical transplantation from NIMA or IPA-mismatched family donor.