Killer‑cell immunoglobulin‑like receptor/human leukocyte antigen‑C combination and ‘great obstetrical syndromes’ (Review)

Abstract

Recurrent pregnancy loss (RPL), pre-eclampsia (PE), fetal growth restriction (FGR), and preterm delivery are examples of 'great obstetrical syndromes' (GOS). Placental dysfunction is the most common pathogenesis of GOS. In human pregnancies, the effects of uterine natural killer cells involve angiogenesis, promoting the remodeling of uterine spiral artery, and improving the invasion of trophoblast cells. The uNK cells supply killer immunoglobulin-like receptors (KIRs), which come into contact with human leukocyte antigen-C (HLA-C) ligands expressed by extravillous trophoblast cells (EVTs). Numerous studies have investigated the association between GOS and KIR/HLA-C combination. However, the outcomes have not been conclusive. The present review aimed to reveal the association between GOS and KIR/HLA-C combination to screen out high-risk pregnancies, strengthen the treatment of pregnancy complications, and reduce the frequency of adverse maternal and fetal outcomes. It has been reported that a female with a KIR AA genotype and a neonate with a paternal HLA-C2 molecule is more prone to develop GOS and have a small fetus since less cytokines were secreted by uNK cells. Conversely, the combination of KIR BB haplotype (including the activating KIR2DS1) and HLA-C2 can induce the production of cytokines and increase trophoblast invasion, leading to the birth of a large fetus. KIR/HLA-C combinations may be applicable in selecting third-party gametes or surrogates. Detection of maternal KIR genes and HLA-C molecules from the couple could serve as useful markers for predicting and diagnosing GOS.

Reproductive Immunology and Pregnancy 2.0

“…Vascular remodeling in PE is accompanied by an increased number of both dNK and cNK cells, exhibiting increased cytolytic activity, which is measured according to the intracellular production of interferon γ (IFN-γ), perforin, and granzyme B [21]. The increased number of NK cells may also be a manifestation of a compensatory mechanism in the event of the insufficient activation of dNK cells, as is the case in an improper combination of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigens (HLA)-C expressed by extravillous trophoblast cells (EVTs) [19,22]. The involvement of NK cells in the pathomechanism of PE is shown in Figure 1.…”