Recurrent Pregnancy Loss in Women with Killer Cell Immunoglobulin-Like Receptor KIR2DS1 is Associated with an Increased HLA-C2 Allelic Frequency

Problem During human pregnancy, the uterine lining is highly populated with killer-immunoglobulin-like receptor (KIR)-expressing NK cells that recognize HLA-C molecules on trophoblast cells. The goal of this study was to analyze the KIR gene contents and frequencies in a N. American cohort of women with RPL of unknown etiology to evaluate whether there is a genetic susceptibility to RPL based on a woman's KIR repertoire and her HLA-C group, as well as the HLA-C group of the partner. Method of study The frequencies of KIR and HLA-C1 and HLA-C2 genes were evaluated in 139 Caucasian women with RPL; HLA-C1, and HLA-C2 group genes were analyzed in their partners (n = 42). The gene frequencies were compared with data reported from corresponding populations. Results Overall, the frequencies of HLA-C groups and KIR genes and genotypes in RPL cohort resembled the frequencies for US Caucasians. The HLAC1 and HLA-C2 group distribution was significantly different between women with or without KIR2DS1. Women positive for KIR2DS1 (45.3% of the study cohort) had an increased frequency of its ligand, HLA-C2 (0.5159 versus 0.3684 in KIR2DS1 negative women, P = 0.014). Conclusion Our results indicate that among KIR2DS1 pos women, the co-expression of HLA-C2 is associated with RPL.