Maternal natural killer cell immunoglobulin receptor genes and human leukocyte antigen-C ligands influence recurrent spontaneous abortion in the Han Chinese population

Abstract

The underlying mechanism of recurrent spontaneous abortion (RSA) has remained elusive for many years. Several previous studies have suggested that the killer cell immunoglobulin receptor (KIR) gene family is associated with RSA, however, it is not clear exactly how. The present study detected KIR and human leukocyte antigen-C (HLA-C) genes in 110 Han Chinese women with unexplained RSA and 105 Han Chinese healthy females. The aim of the present study was to determine if certain genotypes were more susceptible to the occurrence of miscarriage. The frequency of KIR genes and different KIR haplotypes in the 2 groups demonstrated no statistical differences. However, in women who had miscarried ≥3 times, the frequency of KIR3DL1 was significantly reduced and the BB haplotype frequency was significantly higher compared with the control group. HLA-C2C2 was significantly increased in the KIR AB and KIR BB groups in the RSA groups compared with the control group. The women in the RSA group who had a homozygous HLA-C2C2 had a significantly higher frequency of the 2DS1 gene compared with the control group. The reduction of inhibitory gene and increased activation combinations may induce the activation of uterine natural killer cells, which may reduce the probability of fetal survival. To the best of our knowledge, the present study is the first report demonstrating the association between maternal KIR and HLA-C genes and RSA in women of a Han Chinese ethnicity. The present study revealed that females who miscarry ≥3 times may be used as selection criteria for RSA and so may exhibit higher research value.

Genetically Determined Strength of Natural Killer Cells is Enhanced by Adaptive HLA class I Admixture in East Asians

“…These studies also confirmed that KIR and HLA class I combinatorial diversity is an important factor in pregnancy syndromes, infectious disease, blood cancers and transplantation outcome in the Han. They also uncovered both similarities and differences from the specific disease associations observed in Europeans (Bao et al 2016;Jiang et al 2013;Long et al 2015;Shen et al 2016;Su et al 2018). To investigate these findings, we have examined how demographic and evolutionary processes have shaped combinatorial diversity of HLA class I and KIR in the Chinese Southern Han.…”

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows

“…The killer cell immunoglobulin-like receptors (KIR) are a family of inhibitory or activating cell surface receptors expressed on natural killer cells and some T lymphocyte subpopulations [47]. Natural killer cells are granular cells that account for 10-15% of lymphocytes in the blood and serve a vital role in immune regulations and defense [48,49]. Prior to implantation, natural uterine killer cells accumulate and represent the majority of decidua lymphocytes in the endometrium during early pregnancy in humans [48,50].…”

“…Natural killer cells are granular cells that account for 10-15% of lymphocytes in the blood and serve a vital role in immune regulations and defense [48,49]. Prior to implantation, natural uterine killer cells accumulate and represent the majority of decidua lymphocytes in the endometrium during early pregnancy in humans [48,50]. Multiple studies have identified associations with recurrent SA and killer cell immunoglobulin-like receptor proteins in humans [51][52][53][54][55][56][57][58][59][60][61][62], although some studies have refuted these associations [63,64].…”

Adaptive Admixture of HLA Class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians

“…2016 ; Shen et al. 2016 ; Su et al 2018 ). To investigate these findings, we have examined how demographic and evolutionary processes have shaped combinatorial diversity of HLA class I and KIR in the Chinese Southern Han (CHS).…”