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Updated: Aug 16, 2026

Purification of HLA-G+ Extravillous Trophoblasts from Human Term Placental Tissues for Phenotyping and Functional Analysis
Published on: March 13, 2026
Is the HLA System Really Involved in Implantation, Pregnancy, or Abortion of the Fetus?: Strengths, Weaknesses, and
Alicia Hita1, Carmen Botella1, José Antonio Galian1
1Immunology Service, University Clinical Hospital Virgen de La Arrixaca, Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
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.
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