Association of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Class I Ligand with Recurrent Abortion in Saudi Women

Abstract

This study was designed to determine whether genetic polymorphisms of the killer immunoglobulin-like receptor (KIR) and human leukocyte antigen class I (HLA-C) genes are associated with recurrent spontaneous abortion (RSA) in Saudi women. Materials and Methods: Sixty-five healthy women with a history of RSA (three or more spontaneous abortions) and 65 healthy controls (with two or more healthy-born children) living in Riyadh were typed for 17 KIR genes and the HLA-C1 and HLA-C2 allotypes using polymerase chain reaction-sequence-specific primer methodology. Results: The frequencies of KIR2DS2 and KIR2DL5A were significantly lower among RSA women compared to healthy controls (odds ratio [OR] = 0.17; p < 0.001; OR = 0.16; p < 0.001, respectively). No association with maternal HLA-C genotypes was observed. Analysis of KIR-HLA-C combinations indicated a protective effect of KIR2DS2 with its cognate HLA-C1 ligand in both homozygote or heterozygote combinations. Conclusion: Our results demonstrate that the KIR genes of the B haplotype may play an important role in ensuring the success of pregnancy.

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease

“…The analysis of the KIR/HLA-C combination showed the protective effect of KIR2DS2 with the HLA-C1 ligand. There are also reports that the KIR genes of haplotype B may have an impact on pregnancy success [ 88 ]. The possible participation in the initiation of pregnancy has been linked with the presence of the KIR2DL4 receptor.…”

Immunity at maternal–fetal interface: KIR/HLA (Allo)recognition*

“…Specific KIR‐HLA combinations are associated with pregnancy complications like recurrent implantation failure (RIF), recurrent miscarriage, fetal growth restriction (FGR), and preeclampsia 91,103,106,107,114,119,186,216,217. The primary defect in pregnancy disorders is the insufficient uterine lining by an invading EVTs 106 due to dysregulated KIR/HLA allorecognition system is a key player in placentation with focus on KIR/HLA‐C interactions as HLA‐C is the dominant ligand for KIR on dNK cells that may deliver an inhibitory or activating signal 106,119,218 therefore regulating the trophoblast invasion depth 67,103,186,187,216,218,219 . Impact of the maternal KIR and HLA‐C variants as well as paternal HLA‐C haplotype must be considered for investigation of KIR/HLA‐C axis related pregnancy disorders 218 .…”

“…KIR A haplotype was frequently associated with either RIF, RSA, and lower live birth rate in assisted reproduction with double embryo transfer 229 . Recently, interesting data were published from analyzes of peripheral blood samples from women with RSA about significantly lower frequencies of KIR2DS2 and KIR2DL5A as compared to healthy controls with two or more healthy‐born children 219 . They did not found association with maternal HLA‐C genotypes in RSA but report a protective effect of KIR2DS2/HLA‐C1 + combination favoring the protective role of KIR B haplotypes in pregnancy.…”

Natural killer cells and reproductive success

“…Attempts to demonstrate the reproductive impact of specific KIR genes, 33 and specific HLA‐C subtypes 34 have not been successful. That is likely because it is the unique KIR/HLA‐C combination for each pregnancy that is important.…”