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Inherited paternal antigens (IPAs) refer to the set of Human Leukocyte Antigen (HLA) alleles and other polymorphic proteins that an offspring inherits from their father which are not present in the mother (van Rood et al., 2002). During pregnancy, the maternal immune system is exposed to these "foreign" antigens through fetal-maternal microchimerism, which can lead to either the development of immune tolerance or the production of alloantibodies (Ichinohe, 2010). In the field of hematopoietic stem cell transplantation (HSCT), the "IPA effect" is a significant factor in donor selection; for instance, a mother may be a preferred donor for her child because she has been naturally tolerized to the child's IPAs during pregnancy, potentially reducing the risk of graft-versus-host disease (Stern et al., 2008). Conversely, sensitization against IPAs can lead to clinical complications such as hemolytic disease of the fetus and newborn (HDFN) or increased risk of graft rejection in organ transplantation (StatPearls, 2023). While not a single therapeutic target, IPAs are the focus of strategies to manage transplant compatibility and maternal-fetal health through the use of immunosuppressive agents (PubMed, 2021).
Suppression of T-cell and B-cell mediated alloimmune responses against non-self paternal antigens or neutralization of specific antigens to prevent sensitization.
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