Expression of natural cytotoxicity receptor NKp46 on peripheral blood natural killer cells in women with a history of recurrent implantation failures.

Abstract

The peripheral blood natural killer (NK) cells diversity is highly complex; recent studies described more than a thousand phenotypes sharing NK cell receptors, across the leukocyte lineages. In this study, we investigated the expression of NKp46 in peripheral blood NK cells in women with a history of recurrent implantation failures (RIF) with euploid embryos with pre-implantation genetic diagnosis (PGD) and control group (donors of oocytes and surrogate mothers). The expression of NKp46 in peripheral blood lymphocytes and NK cells from women with RIF (n = 57) and control group (n = 50) was analyzed with three-color flow cytometry. The percentage of NKp46+ NK cells was significantly higher in women with RIF compare with the control group and high amount of NKp46+ NK cells (>13% of total lymphocytes) was a poor prognostic factor for embryo implantation. Also, women with RIF had a low amount of NKp46neg NK cells, which was a negative prognostic factor for embryo implantation. The analysis of NK subpopulations, on the basis of NKp46 expression, also revealed that NKp46neg NK in low amounts (<20% of NK cells) and NKp46dim in high amounts (>50% of NK cells) are also negative prognostic factors for embryo implantation. Our results support the clinical significance of the NKp46 expression on NK cells in women with RIF. We suggest that the low level of NKp46neg subset in women with RIF may be a result of an imbalance in the differential development of ILC subsets toward cytotoxic ILC (NK cells), which in turn is a negative condition for successful embryo implantation.