Decreased HLA-C1 alleles in couples of KIR2DL2 positive women with recurrent pregnancy loss. (November 2020) - Yang, Xiuhua
Highlights: Women with KIR2DL2pos had decreased HLA-C1C1 genotype frequencies as compared with those of the general population controls. The partners of women with KIR2DL2pos had increased HLA-C2C2 as compared with those of the general population controls. Allele frequencies of HLA-C specific KIR and KIR genotype frequencies are not different between RPL and general population controls. KIR2DL2 pos/neg and HLA-C group status had no difference irrespective of the pregnancy outcome while on immune-modulation therapy. Women with KIR2DL2pos/HLA-C1C1 had significantly higher peripheral blood NK cell cytotoxicity as compared with that of KIR2DL2pos/HLA-C2C2. Abstract: Specific killer cell immunoglobulin-like receptor (KIR) in women with recurrent pregnancy loss (RPL) and HLA ligands in couples invoke a susceptibility to RPL. However, the relationship between KIR2DL2 and its cognate ligand HLA-C1 has not been explored. In this prospective cohort study, 160 Caucasian women with RPL and 99 partners were included. KIR/HLA-C typing, NK assay, Th1/Th2 intracellular cytokine ratios, 25-(OH)-vitamin D level, and the presence of autoantibodies were analyzed. KIR2DL2 positive women ( P = 0.023) and their partners ( P = 0.017) had lower allele frequencies of HLA-C1 than those of KIR2DL2 negative women. KIR2DL2 positive women had significantly lower genotype frequency of HLA-C1C1 as compared to the North American Caucasian population controls ( P < 0.05). In the partners of KIR2DL2 positive women, there was a substantially higher frequency of HLA-C2C2 than controls ( P = 0.016). Besides, KIR2DL2 negative women had a higher prevalence of anti-ssDNA antibody as compared with that of KIR2DL2 positive women ( P = 0.043). There were no differences in the distribution of HLA-C genotypes based on KIR2DL2, regardless of pregnancy outcome in women with RPL and their partners while on immunomodulation treatment. In conclusion, decreased ligands for inhibitory KIRs (inhKIR) could lead to insufficient inhibition of maternal uterine NK cells toward the trophoblast, thereby contributing to the pathogenesis of RPL. Specific KIR and HLA-C genotyping may predict the reproductive outcome of women with RPL.