The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control.

The invasion of the lining of the uterus by fetal cells known as trophoblasts, which become the main cell type of the placenta. Recurrent miscarriage, preeclampsia, and fetal growth restriction are thought to result from inadequate trophoblast invasion of the uterus lining. Interactions between maternal cells known as uterine NK cells and fetal trophoblasts -- specifically interactions between HLA-C molecules on the fetal trophoblasts and KIRs on the maternal uterine NK cells -- are key to determining the extent of trophoblast invasion. Furthermore, they have determined that the presence of other maternal KIRs that combine with the same HLA-C molecule provides protection against the same common disorders of pregnancy.

We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype.

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John
Editorial Assistant
Immunogenetics Open Access