Kuon R J, Vomstein K, Weber M, Müller F, Seitz C, Wallwiener S, Strowitzki T, Schleussner E, Markert U R, Daniel V, Toth B
Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
Placenta-Lab, Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany.
J Reprod Immunol. 2017 Feb;119:9-14. doi: 10.1016/j.jri.2016.11.002. Epub 2016 Nov 6.
Peripheral and uterine NK cells (pNK, uNK) can be distinguished according to their receptor expression. Recent studies indicate an association of elevated pNK and uNK with recurrent miscarriage (RM). This study aimed to analyze pNK and uNK in patients with RM and healthy controls. Out of n=590 RM patients screened according to a standard diagnostic protocol, n=268 couples with ≥3 consecutive RM were identified. Subgroups consisted of n=151 primary RM (pRM), n=85 secondary RM (sRM), n=32 tertiary RM (tRM) and n=42 healthy controls. Finally, n=147 idiopathic RM (iRM) and n=121 non-iRM patients were identified. Peripheral blood levels of CD45+CD3-CD56+CD16+ NK cells were determined in non-pregnant patients and controls in the mid-luteal phase by FACS. In n=129 RM patients a uterine biopsy was taken to evaluate CD56+ NK cells by immunohistochemistry. PRM showed higher absolute pNK than sRM (median/μl (Q1;Q3): 234 (147;306) vs 176 (128;245), p=0.02). Further a trend towards higher pNK percentages in pRM was detected. UNK numbers did not differ between RM subgroups and did not correlate with pNK. However, the rate of highly elevated uNK was increased in iRM compared to non-iRM patients (p=0.04). Further, higher numbers of CD45+CD3-DR+ (p<0.01) and CD45+CD3+CD8+DR+ (p=0.04) peripheral lymphocytes were associated with higher uNK numbers. In conclusion, elevated pNK were present in pRM patients. Although pNK and uNK numbers did not correlate, the association between high CD45+CD3-DR+ and CD45+CD3+CD8+DR+ peripheral lymphocytes and uNK might indicate that activated NK, B and T cells provide cytokines for the differentiation of uNK.
外周血和子宫自然杀伤细胞（pNK、uNK）可根据其受体表达进行区分。近期研究表明，pNK和uNK水平升高与复发性流产（RM）有关。本研究旨在分析RM患者及健康对照者的pNK和uNK情况。在按照标准诊断方案筛查的n = 590例RM患者中，确定了n = 268对有≥3次连续RM的夫妇。亚组包括n = 151例原发性RM（pRM）、n = 85例继发性RM（sRM）、n = 32例三次发性RM（tRM）和n = 42例健康对照者。最终，确定了n = 147例特发性RM（iRM）患者和n = 121例非iRM患者。在非妊娠患者和对照者的黄体中期，通过流式细胞术检测外周血中CD45 + CD3 - CD56 + CD16 + NK细胞水平。在n = 129例RM患者中进行了子宫活检，通过免疫组织化学评估CD56 + NK细胞。原发性RM患者的绝对pNK水平高于继发性RM患者（中位数/μl（Q1；Q3）：234（147；306）对176（128；245），p = 0.02）。此外，还检测到原发性RM患者的pNK百分比有升高趋势。RM各亚组之间的uNK数量无差异，且与pNK无相关性。然而，与非iRM患者相比，iRM患者中uNK高度升高的比例增加（p = 0.04）。此外，外周血中CD45 + CD3 - DR +（p < 0.01）和CD45 + CD3 + CD8 + DR +（p = 0.04）淋巴细胞数量增加与uNK数量增加有关。总之，原发性RM患者存在pNK水平升高。虽然pNK和uNK数量无相关性，但外周血中高CD45 + CD3 - DR +和CD45 + CD3 + CD8 + DR +淋巴细胞与uNK之间的关联可能表明活化的NK、B和T细胞为uNK的分化提供细胞因子。
