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

Aim: 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).

Methods: 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.

Results: 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 NKp46^neg 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 NKp46^neg NK in low amounts (<20% of NK cells) and NKp46^dim in high amounts (>50% of NK cells) are also negative prognostic factors for embryo implantation.

Conclusion: Our results support the clinical significance of the NKp46 expression on NK cells in women with RIF. We suggest that the low level of NKp46^neg 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.