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DOI: 10.1055/s-0036-1592768
Higher levels of peripheral natural killer cells in patients with primary recurrent miscarriage are associated with altered cytokine profile
Objectives: Natural killer cells (NK cells) are associated with recurrent miscarriage (RM). Elevated levels of NK cells as well as cytokine dysbalances RM have been described in recent studies. However, detailed mechanisms of regulation remain unknown and controversial debates are ongoing. The aim of this study was to identify factors regulating NK cell levels with focus on a high sensitive cytokine assay.
Methods: In total n = 91 couples with ≥3 RM were identified. RM subgroups consisted of n = 53 pRM and n = 38 secondary RM (sRM). Mid-luteal phase peripheral blood was drawn in non-pregnant patients and CD45+CD3-CD56+CD16+ NK cells were determined using four-color fluorescence flow cytometry. Further cytokines were analyzed using LUMINEX technique and highly sensitive cytokine assays (R&D systems).
Results: In our subset of RM patients, higher levels of CD45+CD3-CD56+CD16+ were observed in pRM vs. sRM patients (/ml and %, mean ± SD 290 ± 119, 15.2 ± 5.8 vs. 219 ± 126, 11.6 ± 4.8, p = 0.002, p = 0.008). RANTES (CCL5; 7300 ± 3561 vs. 5774 ± 2952 pg/ml, p = 0.04) and TNF (4,6 ± 3.1 vs. 3.0 ± 2.2 pg/ml, p = 0.03) were higher in pRM patients. Ratios of cytokines reflecting TH1/TH2 profile (INF-g/IL-4, INF-g/IL-10; TNF-a/IL-4, TNF-a/IL-10) showed no significant difference.
Conclusion: NK cells as well as RANTES, TNF differed significantly between pRM and sRM indicating possible effects of previous live birth. However, no significant differences were present with regard to cytokine ratios reflecting TH1/TH2 profile. We hypothesis that NK cells as well as RANTES and TNF might reflect immmunological changes in pRM and sRM patients and help to identify patients which might profit from immunmodulatory treatment.