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Variation of maternal $\textit{KIR }$ and fetal $\textit{HLA-C}$ genes in reproductive failure: too early for clinical intervention

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Chazara, O 
Johnson, MH 

Abstract

A distinctive type of (uterine) natural killer (NK) cell is present in the uterine decidua during the period of placental formation. Uterine NK cells express members of the killer immunoglobulin-like receptor (KIR) family that bind to parental HLA-C molecules on the invading placental trophoblast cells. The maternal KIR genes and their fetal ligands are highly variable, so different KIR/HLA-C genetic combinations occur in each pregnancy. Some women only possess inhibitory KIR genes, whereas other women also express activating KIR genes. The overall signal that NK cells receive from paternal HLA-C on trophoblast depends on the ratio of activating and inhibitory KIR genes expressed by them. Therefore, NK cells provide a balance during placentation to ensure maternal survival and an adequately nourished fetus. Because inhibitory KIRs are found more frequently in women with defective placentation, e.g. pre-eclampsia, fetal growth restriction or recurrent spontaneous abortion, some fertility clinics suggest that women should be 'tissue typed' for their KIR genotypes. We explain why, presently, it is premature to introduce KIR and HLA-C typing to predict pregnancy outcome. In future, however, selecting for certain combinations of KIR and HLA-C variants in surrogacy, egg or sperm donation may prove useful to reduce disorders of pregnancy.

Description

Keywords

HLA-C, KIR, natural killer (NK) cells, placental disorders, tissue typing, trophoblast

Journal Title

Reproductive BioMedicine Online

Conference Name

Journal ISSN

1472-6483
1472-6491

Volume Title

33

Publisher

Elsevier
Sponsorship
Wellcome Trust (085992/Z/08/Z)
Wellcome Trust (090108/Z/09/Z)
Wellcome Trust (100606/Z/12/Z)
Wellcome Trust (088708/Z/09/Z)
British Heart Foundation (None)
MHJ acknowledges support from the Wellcome Trust (088708, 094985 and 100606), which otherwise had no involvement in the research or its publication. AM & FC acknowledge support from the Wellcome Trust (090108/Z/09/Z and 085992/Z/08/Z), the British Heart Foundation (PG/09/077/27964), and the Centre for Trophoblast Research.