Concordance between peripheral and decidual NK cell subsets and killer immunoglobulin-like receptors in women with recurrent spontaneous miscarriages

Background: The role of decidual natural killer (dNK) cells in normal and complicated pregnancy and their relation with peripheral NK (pNK) cells remains unclear. The study aim was phenotypic analysis of pNK and dNK cells at time of miscarriage in recurrent spontaneous miscarriage (RSM) patients to assess whether measuring levels of pNK cell populations can reflect changes in dNK cells or not. Methods: This study included 40 middle aged pregnant women in the 1st trimester subjected to evacuation because of a current miscarriage. They had a history of previous >= two unexplained miscarriages. Frequencies of pNK and dNK cells, based on the expression of CD56, CD16, inhibitory (CD158b) and activating (CD161) Killer immunoglobulin-like receptors (KIRs), were detected by flow cytometry. Results: Percentages of CD56(+) NK cells in peripheral blood and decidua were 17.5 % and 17.3 %, respectively. In both blood and decidua, CD56(dim) NK cells were exceeding CD56(bri)(g)(ht) NK cells. The CD56(dim) CD16(-) NK cells were the predominating subset of NK cells, followed by CD56(dim) CD16(dim). No substantial differences were detected in the levels of KIRs expression by the different NK subsets between blood and decidua. Abnormal upregulation of both CD161 and CD158b on NK cells was observed in blood and decidua. Conclusion: At the time of miscarriage, patients with RSM have an extremely active immune system and an increased number of toxic NK cells both in blood and decidua. The pNK cells reflect dNK cell changes during miscarriage and may be a useful non-invasive predicting tool in reproductive failure setting.