Reproductive Medicine and Immunology, Department of Obstetrics and Gynecology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Vernon Hills, 60061, IL, USA; Clinical Immunology Laboratory, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, 60064, IL, USA; Department of Obstetrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Reproductive Medicine and Immunology, Department of Obstetrics and Gynecology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Vernon Hills, 60061, IL, USA; Clinical Immunology Laboratory, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, 60064, IL, USA.
J Reprod Immunol. 2020 Nov;142:103186. doi: 10.1016/j.jri.2020.103186. Epub 2020 Aug 13.
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.
在复发性妊娠丢失 (RPL) 妇女中，特异性杀伤细胞免疫球蛋白样受体 (KIR) 及其与 HLA 配体的相互作用可导致 RPL 易感性。然而，KIR2DL2 与其同源配体 HLA-C1 之间的关系尚未得到探索。在这项前瞻性队列研究中，纳入了 160 名 RPL 白人妇女及其 99 名伴侣。分析了 KIR/HLA-C 分型、NK 测定、Th1/Th2 细胞内细胞因子比值、25-(OH)-维生素 D 水平和自身抗体的存在。KIR2DL2 阳性妇女 (P=0.023) 和其伴侣 (P=0.017) 的 HLA-C1 等位基因频率低于 KIR2DL2 阴性妇女。与北美白人对照组相比，KIR2DL2 阳性妇女的 HLA-C1C1 基因型频率显著降低 (P<0.05)。在 KIR2DL2 阳性妇女的伴侣中，HLA-C2C2 的频率明显高于对照组 (P=0.016)。此外，与 KIR2DL2 阳性妇女相比，KIR2DL2 阴性妇女抗 ssDNA 抗体的患病率更高 (P=0.043)。无论 RPL 妇女及其伴侣在免疫调节治疗期间的妊娠结局如何，基于 KIR2DL2，HLA-C 基因型的分布没有差异。结论：抑制性 KIR (inhKIR) 的配体减少可能导致母体子宫 NK 细胞对滋养层的抑制不足，从而导致 RPL 的发病机制。特定的 KIR 和 HLA-C 基因分型可能预测 RPL 妇女的生殖结局。
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