Is the HLA System Really Involved in Implantation, Pregnancy, or Abortion of the Fetus?: Strengths, Weaknesses, and Controversial Points
Alicia Hita, Carmen Botella, José Antonio Galian, Rosana González‐López, Marina Fernández‐González, María José Alegría‐Marcos, Rosa Moya‐Quiles, Helios Martínez‐Banaclocha, Manuel Muro‐Pérez, Javier Muro, Alfredo Minguela, Isabel Legaz, Manuel MuroABSTRACT
Problems
Pregnancy is a sensitizing event for human leukocyte antigen (HLA) alleles, as the fetus, acting as a semi‐allograft, expresses maternal and paternal haplotypes in a codominant manner. Consequently, the mother may develop anti‐HLA antibodies directed against the paternal haplotype. However, unlike in organ transplantation, this sensitization is not usually associated with fetal rejection in multiparous women, raising a central question in reproductive immunology: How is maternal‐fetal tolerance achieved and maintained?
Method of Study
This review examines the influence of the HLA system on the immunological mechanisms underlying maternal–fetal tolerance.
Results
Accumulating evidence suggests that this phenomenon results from a complex network of cellular and molecular interactions. The roles of non‐classical HLA molecules, particularly HLA‐G, the modulation of NK activity via KIR receptors, and the expansion of regulatory T cells, which contribute to the maintenance of systemic immunological tolerance, are highlighted. In parallel, the relevance of anti‐HLA antibodies and polymorphisms in HLA regulatory regions in susceptibility to gestational complications has been investigated.
Conclusion
It considers how insights from reproductive immunology may inform related fields such as transplantation and oncology.