Th2/Th3 cytokine genotypes are associated with pregnancy loss

Hum Immunol. 2004 Feb;65(2):135-41. doi: 10.1016/j.humimm.2003.11.007.

Abstract

Cytokines are critical immunoregulatory molecules, responsible for determining the nature of an immune response. It has been proposed that Th2/Th3 immune reactions support normal pregnancy, while Th1 immunity is considered detrimental to the fetus. Since cytokine production is partly under genetic control, it is possible that women suffering from a high incidence of abortions are genetically predisposed to mount a type of immune response inappropriate for pregnancy maintenance. This study investigated the frequencies of cytokine gene polymorphisms in abortion-prone women and women with successful pregnancies. We investigated the role of Th1/Th2/Th3 cytokine gene polymorphisms, such as TGF-beta1 codon 10 (TGFbetac10; C to T), TGF-beta1 codon 25 (TGFbetac25; G to C), TNFalpha promoter-308 (G to A), IL-6 promoter-174 (G to C), IL-10 promoter-1082 (G to A), IL-10 promoter-819 (C to T), IL-10 promoter-592 (C to A), and IFNgamma intron 1 +874 (A to T) in abortion-prone female patients. Our results support the importance of Th2/Th3 immune responses in pregnancy loss, and suggest that an individual's immunogenetic profile indicative of imbalances in Th2/Th3 cytokines is associated with pregnancy loss. Our results suggest that abortive events are determined by genetic factors, reflected in the female patient's immunogenetic profile.

MeSH terms

  • Abortion, Spontaneous / genetics*
  • Abortion, Spontaneous / immunology
  • Cytokines / genetics*
  • Cytokines / immunology
  • Data Interpretation, Statistical
  • Embryo Loss / genetics
  • Embryo Loss / immunology
  • Female
  • Gene Frequency
  • Genotype
  • Gravidity / genetics
  • Gravidity / immunology
  • Haplotypes / genetics
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Parity / genetics
  • Parity / immunology
  • Polymorphism, Genetic
  • Pregnancy
  • Promoter Regions, Genetic / genetics
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th2 Cells / immunology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Cytokines
  • Interleukin-6
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma