Strobel Laura, Vomstein Kilian, Kyvelidou Christiana, Hofer-Tollinger Susanne, Feil Katharina, Kuon Ruben-Jeremias, Ebner Susanne, Troppmair Jakob, Toth Bettina
Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
J Clin Med. 2021 Jan 7;10(2):194. doi: 10.3390/jcm10020194.
(1) Background: Prior studies suggested a significant impact of previous live births on peripheral natural killer cells (pNK) in patients with recurrent pregnancy loss (RPL). Patients with primary RPL (pRPL, no live birth) showed higher numbers of pNK than secondary RPL patients (sRPL, ≥ 1 live birth). (2) Methods: To further determine immunological differences between RPL patients and controls, we analysed pNK subpopulations and activation markers in pRPL ( = 47), sRPL ( = 24) and controls with previous live birth (sCtrl, = 25) and nullipara (pCtrl, = 60) within a prospective study. Percentages and numbers of CD56CD16 cells, subpopulations and activation markers (CD57+, CD62L+, NKG2D+, NKp46+) were measured in non-pregnant RPL patients and = 85 controls ( = 60 pCtrl, = 25 sCtrl) in the mid-luteal phase by flow cytometry. (3) Results: Compared to sRPL patients, sCtrls showed higher CD56 and CD56CD16 numbers. Further, sRPL patients showed lower numbers of CD56CD16NKG2D and CD56CD16NKp46 than sCtrls. (4) Conclusion: We suggest a chronic immune stimulation leading to a lower NK-cell count in sRPL patients with a lower NK cytotoxicity. This underlines the necessity to investigate pNK subpopulations as well as pRPL and sRPL separately to delineate the immune alterations in RPL.
(1)背景:先前的研究表明,既往活产对复发性流产(RPL)患者外周自然杀伤细胞(pNK)有显著影响。原发性RPL(pRPL,无活产)患者的pNK数量高于继发性RPL患者(sRPL,≥1次活产)。(2)方法:为进一步确定RPL患者与对照组之间的免疫学差异,我们在一项前瞻性研究中分析了pRPL(n = 47)、sRPL(n = 24)以及有既往活产史的对照组(sCtrl,n = 25)和未生育对照组(pCtrl,n = 60)的pNK亚群和激活标志物。在黄体中期,通过流式细胞术检测未孕RPL患者和85名对照组(60名pCtrl,25名sCtrl)中CD56⁺CD16⁻细胞的百分比和数量、亚群以及激活标志物(CD57⁺、CD62L⁺、NKG2D⁺、NKp46⁺)。(3)结果:与sRPL患者相比,sCtrl组的CD56⁺和CD56⁺CD16⁻细胞数量更多。此外,sRPL患者的CD56⁺CD16⁻NKG2D⁺和CD56⁺CD16⁻NKp46⁺细胞数量低于sCtrl组。(4)结论:我们认为存在慢性免疫刺激,导致sRPL患者的NK细胞计数较低且NK细胞毒性较低。这强调了分别研究pNK亚群以及pRPL和sRPL以明确RPL免疫改变的必要性。