Combinations of Maternal KIR and Fetal HLA-C Genes Influence the Risk of Preeclampsia and Reproductive Success

By S. Hiby, James J. Walker, K. O’Shaughnessy, Christopher W. G. Redman, M. Carrington, J. Trowsdale, A. Moffett. Journal of Experimental Medicine, 2004

1,119 citations recorded by the source corpus.

Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms.

Subfields: Immunology, Obstetrics and Gynecology

View Paper: https://www.semanticscholar.org/paper/735aa0209edb7aa21d3f0375bc7d312aea9ec989

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Moffett
2. C. Loke
3. M. Peterson
4. S. Rajagopalan
5. H. Kim
6. Peter Parham
7. Eric O Long
8. Dongfang Liu

Citations in the corpus

• Immunology of placentation in eutherian mammals (2006, result): “This hypothesis is supported by a recent study showing that the occurrence of pre-eclampsia is associated with an increased frequency of maternal KIRs of the AA genotype but only when this is combined with the presence of an HLA-C2 allotype in the fetu”
• Controlling NK Cell Responses: Integration of Signals for Activation and Inhibition (2013, background): “Genetic studies have revealed that certain activating KIRs, in combination with specific MHC-I ligands, may provide protection from progression to AIDS in HIV-infected individuals (29) and from preeclampsia in pregnant mothers (30).”
• Decidual NK cells regulate key developmental processes at the human fetal-maternal interface (2006, background): “, and a ligand expression pattern on fetal trophoblasts favoring stimulation of inhibitory receptors on dNK cells is unexpectedly associated with increased risk for preeclampsi”
• MHC class I molecules and kirs in human history, health and survival (2005, result): “By contrast, a recent paper identifies a spectrum of risk for pre-eclampsia that correlates with the combination of maternal KIR genotype and fetal HLA-C typ”