P120 Predicted indirectly recognizable HLA epitopes presented by HLA-DRB1 are related to HLA antibody formation during pregnancy

Abstract

Aim Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes presented by recipient HLA class-II (PIRCHE-II). In the present study we evaluated the role of PIRCHE-II in the child-specific HLA antibody formation during pregnancy. Methods A total of 229 mother–child pairs were HLA-typed. For all mismatched HLA class-I molecules of the child (inherited paternal antigens (IPA), we subsequently predicted the number of HLA epitopes that can be presented by maternal HLA class-II molecules. Child-specific antigens were classified as either immunogenic HLA or non-immunogenic HLA based upon the presence of specific antibodies and correlated to PIRCHE-II numbers. Results Immunogenic HLA contained higher numbers of PIRCHE-II than non-immunogenic HLA (median increases 1.3-fold). Moreover, the probability of IPA-specific antibody production during pregnancy increased with the number of PIRCHE-II. Conclusions In conclusion, our data suggest that the number of PIRCHE-II is related to the formation of child-specific HLA antibodies during pregnancy. The present confirmation of the role of PIRCHE-II in antibody formation outside the transplantation setting suggests that the PIRCHE-II concept is a universal principle.