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.

复发性流产 (RPL) 妇女中的特异性杀伤细胞免疫球蛋白样受体 (KIR) 和夫妻中的 HLA 配体引起对 RPL 的易感性。然而，尚未探索 KIR2DL2 与其同源配体 HLA-C1 之间的关系。在这项前瞻性队列研究中，包括 160 名患有 RPL 的白人女性和 99 名伴侣。分析了 KIR/HLA-C 分型、NK 测定、Th1/Th2 细胞内细胞因子比率、25-(OH)-维生素 D 水平和自身抗体的存在。KIR2DL2 阳性女性（P  = 0.023）及其伴侣（P  = 0.017）的 HLA-C1 等位基因频率低于 KIR2DL2 阴性女性。与北美高加索人群对照相比，KIR2DL2 阳性女性的 HLA-C1C1 基因型频率显着降低（P < 0.05)。在 KIR2DL2 阳性女性的伴侣中，HLA-C2C2 的频率明显高于对照组（P  = 0.016）。此外，与 KIR2DL2 阳性女性相比，KIR2DL2 阴性女性抗 ssDNA 抗体的患病率更高（P  = 0.043）。无论 RPL 女性及其伴侣在接受免疫调节治疗时的妊娠结果如何，基于 KIR2DL2 的 HLA-C 基因型分布没有差异。总之，抑制性 KIR (inhKIR) 配体的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 基因分型可以预测 RPL 女性的生殖结果。