IVF助孕妊娠患者γδT细胞和NK细胞检测的临床意义

doi:10.3969/j.issn.1673-8640.2025.06.007

摘要/Abstract

摘要：

目的探讨既往有自然流产史，经体外受精（IVF）助孕妊娠患者外周血γδT细胞、自然杀伤（NK）细胞变化的临床意义。方法选取2022年3月—2023年3月大连市妇女儿童医疗中心（集团）既往有自然流产史且本次行IVF助孕并成功妊娠的患者45例，根据本次妊娠是否发生早期流产分为正常妊娠组和稽留流产组；以同期自然受孕的早孕期女性27名作为正常对照组。收集所有研究对象的临床资料，采用流式细胞术检测外周血γδT细胞百分比和NK细胞百分比。结果与正常对照组比较，正常妊娠组和稽留流产组γδT细胞百分比均显著升高（P<0.05）；正常妊娠组与稽留流产组之间差异无统计学意义（P>0.05）。稽留流产组NK细胞百分比显著高于正常妊娠组（P<0.05），与正常对照组比较差异无统计学意义（P>0.05）。正常对照组、正常妊娠组、稽留流产组高龄（≥35岁）者与非高龄（<35岁）者之间γδT细胞百分比和NK细胞百分比差异均无统计学意义（P>0.05）。正常妊娠组和稽留流产组首次流产（流产次数=1）者与复发性流产（流产次数≥2）者之间γδT细胞百分比和NK细胞百分比差异均无统计学意义（P>0.05）。结论 γδT细胞和NK细胞或可作为既往有自然流产史，经IVF助孕妊娠患者免疫状态的监测指标。

关键词: γδT细胞, 自然杀伤细胞, 体外受精, 自然流产

Abstract:

Objective To investigate the clinical significance of the changes of γδT cells and natural killer（NK） cells in the peripheral blood of pregnant patients with a previous history of spontaneous abortion and assisted pregnancy through in vitro fertilization（IVF）. Methods Totally，45 patients with a history of spontaneous abortion in Dalian Women and Children Medical Group from March 2022 to March 2023 who successfully became pregnant after undergoing IVF were enrolled. They were classified into normal pregnancy group and missed abortion group according to whether early abortion occurred at the present stage. Totally，27 females in the early pregnancy who were pregnant naturally during the same period were enrolled as control group. The clinical data of all the research subjects were collected，and the percentages of γδT cells and NK cells in peripheral blood were determined by flow cytometry. Results Compared with control group，the percentages of γδT cells in both normal pregnancy group and missed abortion group were increased（P<0.05）. There was no statistical significance between normal pregnancy group and missed abortion group（P>0.05）. The percentage of NK cells in missed abortion group was higher than that in normal pregnancy group（P<0.05），and there was no statistical significance compared with control group（P>0.05）. There was no statistical significance in the percentages of γδT cells and NK cells between elderly（≥35 years old） and non-elderly（<35 years old） in control group，normal pregnancy group and missed abortion group（P>0.05）. There was no statistical significance in the percentages of γδT cells and NK cells between those with the first abortion（number of abortion=1） and those with recurrent abortion（number of abortion≥2） in normal pregnancy group and missed abortion group（P>0.05）. Conclusions γδT cells and NK cells may serve as monitoring indicators for the immune status of patients with a history of spontaneous abortion and assisted pregnancy through IVF.

Key words: γδT cell, Natural killer cell, In vitro fertilization, Spontaneous abortion

中图分类号:

R446.6

刘小雪, 杨惠云, 朱文秀, 刘胜欢, 石铭. IVF助孕妊娠患者γδT细胞和NK细胞检测的临床意义[J]. 检验医学, 2025, 40(6): 555-559.

LIU Xiaoxue, YANG Huiyun, ZHU Wenxiu, LIU Shenghuan, SHI Ming. Clinical roles of γδT cell and NK cell determinations in pregnant patients through IVF[J]. Laboratory Medicine, 2025, 40(6): 555-559.

图/表 6

参考文献 20

[1]	李聪聪, 赵爱民. 不明原因复发性流产的免疫指标筛查及诊治策略[J]. 实用妇产科杂志, 2021, 37(8):567-570.
[2]	OIKONOMOU G, VLACHADIS N, TSAMADIAS V, et al. Human leukocyte antigen alleles compatibility and immunophenotypic profile associations in infertile couples[J]. Cureus, 2023, 15(3):e36584.
[3]	LA X, WANG W, ZHANG M, et al. Definition and multiple factors of recurrent spontaneous abortion[J]. Adv Exp Med Biol, 2021, 1300:231-257. DOI PMID
[4]	MORANDI F, YAZDANIFAR M, COCCO C, et al. Engineering the bridge between innate and adaptive immunity for cancer immunotherapy:focus on γδ T and NK cells[J]. Cells, 2020, 9(8):1757.
[5]	SESHADRI S, SUNKARA S K. Natural killer cells in female infertility and recurrent miscarriage:a systematic review and meta-analysis[J]. Hum Reprod Update, 2014, 20(3):429-438.
[6]	自然流产诊治中国专家共识编写组. 自然流产诊治中国专家共识(2020年版)[J]. 中国实用妇科与产科杂志, 2020, 36(11):1082-1090. DOI
[7]	HUANG C, ZHANG Y, XIANG Z, et al. Granzyme B-expressing γδ-T and NK cells as a predictor of clinical pregnancy failure in patients with unexplained repeated implantation failure[J]. J Reprod Immunol, 2021, 144:103269.
[8]	WANG Y, SUN Y, DI W, et al. Association between induced abortion history and later in vitro fertilization outcomes[J]. Int J Gynaecol Obstet, 2018, 141(3):321-326.
[9]	BAFOR E E, VALENCIA J C, YOUNG H A. Double negative T regulatory cells:an emerging paradigm shift in reproductive immune tolerance?[J]. Front Immunol, 2022, 13:886645.
[10]	BIAN Q, FU B. Immunological microenvironment at the maternal-fetal interface[J]. J Reprod Immunol, 2022, 151:103632.
[11]	TALUKDAR A, RAI R, APARNA SHARMA K, et al. Peripheral gamma delta T cells secrete inflammatory cytokines in women with idiopathic recurrent pregnancy loss[J]. Cytokine, 2018, 102:117-122. DOI PMID
[12]	HAYDAY A C. Gammadelta T cells and the lymphoid stress-surveillance response[J]. Immunity, 2009, 31(2):184-196. DOI PMID
[13]	XU Q H, LIU H, WANG L L, et al. Roles of γδT cells in pregnancy and pregnancy-related complications[J]. Am J Reprod Immunol, 2021, 86(5):e13487.
[14]	李燕滨, 王玲, 吴涢婷, 等. NK细胞在免疫异常自然流产中的研究进展[J]. 中国当代医药, 2020, 27(19):17-21.
[15]	王玲, 李燕滨, 陈锦红, 等. 高龄孕妇妊娠早期外周血自然杀伤细胞与先兆流产的相关性研究[J]. 发育医学电子杂志, 2021, 9(6):443-448.
[16]	CHOUDHURY R H, DUNK C E, LYE S J, et al. Extravillous trophoblast and endothelial cell crosstalk mediates leukocyte infiltration to the early remodeling decidual spiral arteriole wall[J]. J Immunol, 2017, 198(10):4115-4128. DOI PMID
[17]	LIU Y, GAO S, ZHAO Y, et al. Decidual natural killer cells:a good nanny at the maternal-fetal interface during early pregnancy[J]. Front Immunol, 2021, 12:663660.
[18]	XIAO H, LIN R, CHEN C, et al. γδ-T cell with high toxic potential was associated with recurrent miscarriage[J]. Am J Reprod Immunol, 2023, 90(1):e13717.
[19]	DU M, LI Y, GU H, et al. Assessment of the risk of unexplained recurrent spontaneous abortion based on the proportion and correlation of NK cells and T cells in peripheral blood[J]. Technol Health Care, 2023, 31(S1):97-109. DOI PMID
[20]	张倩, 杜琛, 陈秀娟, 等. 免疫因素与复发性流产的相关性分析[J]. 生殖医学杂志, 2023, 32(12):1915-1921.

组别	例数	年龄/岁	孕次/次	不孕年限/年	流产次数/次
正常妊娠组	25	35.0±3.2	2.9±1.5	4.0±2.9	2.3±1.4
稽留流产组	20	34.5±4.7	2.4±1.0	4.6±2.5	2.2±0.9
正常对照组	27	32.0±3.3	2.3±0.7

组别	例数	年龄/岁	孕次/次	不孕年限/年	流产次数/次
正常妊娠组	25	35.0±3.2	2.9±1.5	4.0±2.9	2.3±1.4
稽留流产组	20	34.5±4.7	2.4±1.0	4.6±2.5	2.2±0.9
正常对照组	27	32.0±3.3	2.3±0.7

组别	例数	γδT细胞/%	NK细胞/%
正常对照组
高龄	6	6.9（6.1，8.6）	21.5（12.0，25.1）
非高龄	21	5.8（5.2，8.8）	18.2（13.7，26.1）
正常妊娠组
高龄	10	8.9（5.6，14.3）	14.5（12.7，23.1）
非高龄	15	9.6（6.7，12.1）	13.2（11.4，21.7）
稽留流产组
高龄	11	7.7（5.9，11.3）	16.8（14.6，26.8）
非高龄	9	10.6（5.5，14.9）	18.1（12.0，30.4）

组别	例数	γδT细胞/%	NK细胞/%
正常对照组
高龄	6	6.9（6.1，8.6）	21.5（12.0，25.1）
非高龄	21	5.8（5.2，8.8）	18.2（13.7，26.1）
正常妊娠组
高龄	10	8.9（5.6，14.3）	14.5（12.7，23.1）
非高龄	15	9.6（6.7，12.1）	13.2（11.4，21.7）
稽留流产组
高龄	11	7.7（5.9，11.3）	16.8（14.6，26.8）
非高龄	9	10.6（5.5，14.9）	18.1（12.0，30.4）

组别	例数	γδT细胞/%	NK细胞/%
正常妊娠组
首次流产	16	9.4 （6.2，13.4）	15.0 （11.8，22.2）
复发性流产	9	9.6 （7.5，11.8）	12.7 （11.5，21.5）
稽留流产组
首次流产	5	11.3 （8.3，17.2）	13.6 （12.0，21.7）
复发性流产	15	7.7 （5.4，12.1）	22.4 （14.6，29.1）