Increased NK-cell subsets with inhibitory cytokines and surface receptors in patients with recurrent miscarriage
20 September 2018 (online)
Aim of the study:
NK-cells are in the focus of debate as potential immunologic markers and targets in recurrent miscarriage (RM). The aim of this study was to identify differences in counter-regulating inhibitory mechanisms of NK-cell subsets in patients with RM compared to healthy controls.
In this prospective cohort study, n = 31 patients with idiopathic RM and n = 37 healthy controls were recruited between 01/2016 and 09/2017. NK-, NKT- and T-cell subsets were analyzed in both groups using eight-color fluorescence flow cytometry. Patients had a history of 3 and more consecutive miscarriages and were screened for anatomical, endocrine, autoimmune and thrombophilic disorders as well as parental chromosomal abnormalities.
Compared with healthy controls, patients with RM showed significantly higher absolute numbers of CD56+ NK cells co-expressing the phenotype IFNyR+, IL4+, TGFβ+, IL4+HLADR+, TGFβ+HLADR+, IL4+TGFβ+, IL4+TGFβ-, IFNy+ and/or IL10- IFNy+ (all p ≤0.01), more IL17+CD56bright (p = 0.028) NK cells, and more CD56dimCD16+ NK cells co-expressing IFNyR, IFNy, IL4 and/or TGFβ (all p ≤0.01). Further, patients with RM showed significantly higher absolute numbers of CD158a-CD158e+, CD158a+, CD158b+ (all p < 0.05), NKG2D+NKG2A+, NKG2D+NKG2A-, NKG2D+ and/or NKG2A+ (all p ≤0.01) CD56+ NK cells and higher CD158a+, CD158b+ (all p < 0.05), NKG2D+ and/or NKG2A+ (all p < 0.01) CD56dim+CD16+ NK cells.
Compared to healthy controls, patients with RM have abnormal high circulating NK cells expressing inhibitory cytokines and inhibitory surface receptors which might contribute to the pathogenesis. This immune profile might be used to identify patients that benefit from therapies that inhibit cytotoxic immune response in clinical trials.