Profiling NK cell receptor repertoire of women with idiopathic recurrent pregnancy loss

Natural killer (NK) cells have been extensively studied to understand the pathophysiology of idiopathic recurrent pregnancy loss (iRPL), however a clear association between NK cell frequency and iRPL has yet to be established. Most studies have focused on peripheral NK (pNK) cells, which may not accurately reflect the uterine immune environment. This study aimed to investigate the receptor repertoire of uterine NK (uNK) cells derived from menstrual blood in women with iRPL (n = 20) and compare it to controls with uncomplicated pregnancies (n = 16). The uNK cell receptor analysis revealed a significant reduction in the expression intensities of 2B4 and NKp44 on several uNK cell clusters in women with iRPL. In addition, stratification by cytomegalovirus (CMV) seropositivity revealed that CMV-positive women had significantly higher NKp44 expression on uNK cells and frequencies of NKG2A+KIRs+LILRB1+NKG2C-uNK cells (10.3 % vs. 4.2 %, p = 0.025) compared to CMVnegative women. Surprisingly, this population was lowest in women with primary iRPL compared to secondary iRPL and control subjects (2.6 % vs. 8.6 %, 12.8 %, p = 0.005). These findings highlight differences in uNK cell receptor repertoire of women with iRPL and indicate that live birth history and CMV seropositivity influence uNK cells.