title: Variation of maternal KIR and fetal HLA-C genes in reproductive failure: too early for clinical intervention.
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.
authors.affiliation: Dept of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. Electronic address: am485@cam.ac.uk.
authors.forename: Ashley
authors.initials: A
authors.lastname: Moffett
authors.affiliation: Dept of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Olympe
authors.initials: O
authors.lastname: Chazara
authors.affiliation: Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Department of Obstetrics and Gynaecology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Colucci
authors.affiliation: Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Johnson
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology; D015331:Cohort Studies; D003656:Decidua / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007246:Infertility / Q000235:genetics*; D007694:Killer Cells, Natural / Q000378:metabolism; D008024:Ligands; D010920:Placenta / Q000378:metabolism; D010929:Placentation; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D054342:Receptors, KIR2DL1 / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D012098:Reproduction; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
chemical_list: D000939:Epitopes; D015236:HLA-C Antigens; C093100:KIR2DL1 protein, human; D008024:Ligands; D054342:Receptors, KIR2DL1
keywords: HLA-C; KIR; natural killer (NK) cells; placental disorders; tissue typing; trophoblast