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J Assist Reprod Genet. 2019 Mar 7. doi: 10.1007/s10815-019-01426-9. [Epub ahead of print]

Understanding the role of killer cell immunoglobulin-like receptors in pregnancy complications.

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Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain.
Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile.
IVI-RMA, Fundación IVI; INCLIVA, IIS La Fe, Valencia University, Valencia, Spain.
Faculty of Sport Sciences and Instituto de Investigación Hospital 12 de Octubre, Universidad Europea de Madrid, Madrid, Spain.
Inmunología, Centro de Investigaciones Biomédicas (CINBIO), Universidade de Vigo, Vigo, Spain.


Pregnancy is a unique immunological situation in which a fetus-bearing paternal histocompatibility antigens can survive in a maternal environment without apparent rejection. To face this challenge, cells of the uterine immune system show characteristic changes in absolute number and composition during pregnancy. Particularly relevant to this process are uterine natural killer (uNK) cells and their cell surface receptors, killer immunoglobulin-like receptors (KIRs). The main purpose of this review is to outline the current body of knowledge on the involvement of KIRs in the complications of pregnancy. Implantation depends on the invasion of embryonic trophoblast cells into maternal uterine tissue and remodeling of the uterine spiral arterioles, which is essential for placental perfusion and successful pregnancy. The proper interaction between maternal KIRs and their ligands human leukocyte antigen (HLA) class I molecules, expressed by the extravillous trophoblast cells, is crucial in this process. KIRs are a complex family that includes both activator and inhibitory receptors. The activation profile is genetically determined in each individual and leads to diverse levels of functionality for NK and T cells on engagement with specific HLA class I molecules. An association between different KIR alleles and HLA molecules has been reported in pregnancy complications, supporting the idea of a relevant role of these receptors in successful pregnancy.


Extravillous trophoblast; HLA; KIR; Recurrent miscarriage; Uterine natural killer


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