A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures

Aim: NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. Methods: In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th-7th week of gestation-w.g.) and 66 women in the 11th-13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. Results: A misbalance in the NKp46(+)NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46(high) cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46(hight)CD56(++)) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Conclusions: Our results showed that accentuated levels of NKp46(+)NK cells lead to a negative prognosis for early pregnancy courses in women.