Pregnancy Immunogenetics and Genomics: Implications for Pregnancy-Related Complications and Autoimmune Disease

Annu Rev Genomics Hum Genet. 2019 Aug 31:20:73-97. doi: 10.1146/annurev-genom-083118-014943. Epub 2019 Mar 8.

Abstract

Pregnancy presents a singular physiological scenario during which the maternal immune system must accommodate the semiallogeneic fetus. Fluctuations between pro- and anti-inflammatory states are required throughout gestation to facilitate uterine tissue remodeling, fetal growth and development, and finally birth. Tolerance for the fetus must be established and maintained without fundamentally compromising the maternal immune system function, so that both the mother and fetus are protected from foreign insults. Here, we review our current understanding of how genetic variation at both maternal and fetal loci affects implantation and placenta formation, thereby determining the likelihood of a successful pregnancy outcome or the development of pregnancy-related complications. We also consider the impact of pregnancy on both the maternal and fetal systemic immune systems and the related implications for modulating ongoing autoimmune diseases and triggering their development.

Keywords: HLA; KIR; allorecognition; autoimmunity; pregnancy; tolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Female
  • Fetus / immunology*
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental
  • Genetic Loci
  • Genetic Variation
  • Genome, Human / immunology*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Immune System / growth & development
  • Immune System / metabolism*
  • Immune Tolerance
  • Immunogenetics / methods
  • Placenta / immunology*
  • Placenta / metabolism
  • Pregnancy
  • Pregnancy Complications / genetics*
  • Pregnancy Complications / immunology
  • Pregnancy Complications / pathology
  • Receptors, KIR / genetics
  • Receptors, KIR / immunology

Substances

  • HLA Antigens
  • Receptors, KIR