KIR (Killer-cell immunoglobulin-like receptor) haplotype evaluation

The KIR haplotype (A/B) determination method allows for the identification of the mother's genetic makeup in the region of KIR receptors. These receptors play a crucial role in the communication between the mother's immune system and the embryo during pregnancy, where they recognize HLA-C molecules on the embryo's surface. Analysis of the KIR haplotype can help reveal specific maternal genotypes that, in combination with the fetal HLA-C, may be associated with a higher risk of pregnancy complications.

KIR haplotype (A/B) determination is a genetic analysis performed using the polymerase chain reaction with sequence-specific primers (PCR-SSP) method with an IVD kit. This method allows for the determination of the genetic variant (haplotype) of the genes encoding KIR (Killer-cell Immunoglobulin-like Receptors) in the mother.

Maternal immunotolerance towards the developing embryo is crucial for a successful full-term pregnancy. This complex process involves the interaction between maternal immune cells present in the uterus, particularly uterine Natural Killer (uNK) cells, and the embryo. uNK cells express receptors called KIRs on their surface, which recognize specific HLA-C molecules present on the embryo's surface. This interaction between maternal KIR receptors and fetal HLA-C molecules plays a key role in regulating the immune response at the maternal-fetal interface.

The genes encoding KIR receptors are located on chromosome 19q13.4 in a region known as the leukocyte receptor complex. Currently, a total of 17 different KIR genes are known, which are divided into nine genes for inhibitory receptors, six genes for activating receptors, and two pseudogenes (non-functional genes). Based on the combination of these genes, two main KIR haplotypes are distinguished: haplotype A (KIR A) and haplotype B (KIR B). KIR haplotypes represent specific arrangements of the centromeric and telomeric regions of this gene complex, with frequent recombinations occurring in this region, contributing to high genetic variability among individuals. During pregnancy, a mother can have one of three basic KIR genotypes: AA (with a predominance of inhibitory KIRs), AB (a combination of inhibitory and activating KIRs), or BB (with a higher number of activating KIRs).

HLA-C gene, which belong to the major histocompatibility complex class I (HLA class I) group, is located on the short arm of chromosome 6. HLA-C has particular significance in pregnancy because it is the only classical HLA class I gene expressed at the maternal-fetal interface. HLA-C molecules serve as ligands (binding sites) for KIR receptors on uNK cells. These ligands are divided into two main groups: HLA-C1 and HLA-C2. HLA-C2 ligands exhibit a stronger binding affinity to certain activating KIR receptors than HLA-C1 ligands.

Several studies suggest that certain combinations of maternal KIR haplotype and fetal HLA-C genotype can influence the course of pregnancy and be associated with a higher risk of complications. For example, in women with the KIR AA genotype carrying a fetus with HLA-C2, insufficient activation of uNK cells may occur, which can negatively affect implantation and placentation, leading to recurrent miscarriages, preeclampsia, or intrauterine growth restriction. Therefore, determining the maternal KIR haplotype can provide valuable information in the context of reproductive health and pregnancy planning.