系统性红斑狼疮患者妊娠期外周血中滤泡辅助性T淋巴细胞的变化及其意义

doi:10.13481/j.1671-587X.20230121

吉林大学学报(医学版) ›› 2023, Vol. 49 ›› Issue (1): 166-172.doi: 10.13481/j.1671-587X.20230121

• 临床研究 • 上一篇

系统性红斑狼疮患者妊娠期外周血中滤泡辅助性T淋巴细胞的变化及其意义

白杨¹,杨晨曦²,刘小强²,刘羽³(),邢倩⁴()

^1.潍坊医学院临床医学院风湿免疫科，山东潍坊 261000
^2.山东省青岛市妇女儿童医院生殖医学科，山东青岛 266000
^3.山东省青岛市妇女儿童医院产科，山东青岛 266000
^4.山东省青岛市市立医院风湿免疫科，山东青岛 266000

收稿日期:2022-06-22 出版日期:2023-01-28 发布日期:2023-02-03
通讯作者: 刘羽,邢倩 E-mail:qingdaofer@163.com;gdz696@163.com
作者简介:白杨（1996－），男，山东省济南市人，在读硕士研究生，主要从事风湿免疫性疾病方面的研究。
基金资助:
山东省卫健委计划项目(2019WS147)

Changes of follicular helper T lymphocytes in peripheral blood of patients with systemic lupus erythematosus during pregnancy and its significance

Yang BAI¹,Chenxi YANG²,Xiaoqiang LIU²,Yu LIU³(),Qian XING⁴()

^1.Department of Rheumatology，College of Clinical Medical Sciences，Weifang Medical College，Shandong Province，Weifang 261000，China
^2.Department of Reproductive Medicine，Qingdao Women and Children Hospital，Shandong Province，Qingdao 266000，China
^3.Department of Obstetrics，Qingdao Women and Children Hospital，Shandong Province，Qingdao 266000，China
^4.Department of Rheumatology，Qingdao Municipal Hospital，Shandong Province，Qingdao 266000，China

Received:2022-06-22 Online:2023-01-28 Published:2023-02-03
Contact: Yu LIU,Qian XING E-mail:qingdaofer@163.com;gdz696@163.com

摘要/Abstract

摘要：

目的探讨系统性红斑狼疮（SLE）患者妊娠期外周血中滤泡辅助性T淋巴细胞（Tfh）的变化，并阐明Tfh细胞在妊娠期SLE患者中的免疫作用。方法选取来自山东省青岛市市立医院和青岛市妇女儿童医院就诊的SLE患者，分为SLE妊娠组32例和SLE未妊娠组30例，以健康妊娠组（健康妊娠妇女）30例和健康未妊娠组（健康未妊娠妇女）25例为对照，SLE妊娠组32例患者（随访丢失2例）根据妊娠期间和终止妊娠后3个月内病情变化分为SLE妊娠预后不良组（8例）和SLE妊娠临床稳定组（22例），收集各组受试者临床资料和实验室检查指标。采用流式细胞术检测各组受试者外周血中CD4+诱导性T细胞共刺激因子（ICOS）+趋化因子C-X-C-基元受体5（CXCR5）+Tfh细胞占CD4+T淋巴细胞百分率（Tfh细胞百分率），采用Spearman相关分析检验SLE妊娠组患者外周血中Tfh细胞百分率与患者实验室检查指标的相关性，采用酶联免疫吸附试验（ELISA）法检测各组受试者外周血中白细胞介素6（IL-6）、白细胞介素21（IL-21）和干扰素γ（IFN-γ）水平。结果与健康妊娠组比较，SLE妊娠组患者外周血中Tfh细胞百分率明显升高（P<0.01），健康未妊娠组受试者外周血中Tfh细胞百分率明显降低（P<0.05）；与SLE未妊娠组比较，SLE妊娠组患者外周血中Tfh细胞百分率明显升高（P<0.05）。随访中，与SLE妊娠临床稳定组比较，SLE妊娠预后不良组患者外周血中Tfh细胞百分率明显升高（P<0.05）。SLE妊娠组患者外周血中Tfh细胞百分率与抗心磷脂抗体（ACA）-IgG和抗β2糖蛋白Ⅰ（β2GPⅠ）抗体滴度均呈正相关关系（r=0.743 1，P<0.05；r=0.830 7，P<0.01）。与健康妊娠组比较，SLE妊娠组患者外周血中IL-6和IL-21水平明显升高（P<0.05）；与SLE未妊娠组比较，SLE妊娠组患者外周血中IL-21水平明显升高（P<0.05）。结论 SLE患者妊娠早期外周血中Tfh细胞百分率升高可能与SLE患者妊娠预后不良有关。

关键词: 滤泡辅助性T淋巴细胞, 系统性红斑狼疮, 妊娠, 预后

Abstract:

Objective To investigate the changes of follicular helper T lymphocytes （Tfh） in peripheral blood of the patients with systemic lupus erythematosus （SLE） during pregnancy， and to clarify the immune effects of Tfh cells duing pregnancy. Methods The SLE patients from Qingdao Municipal Hospital and Qingdao Women and Children Hospital were divided into SLE with pregnancy group （n=32） and SLE without pregnancy group （n=30）；at the same time， healthy pregnancy group （healthy pregnancy women，n = 30） and healthy non-pregnancy group（healthy non-pregnancy women，n=25） were used as control. According to the changes of lupus during pregnancy and after termination of pregnancy within 3 months， the 32 cases of SLE patients in SLE with pregnancy group （2 cases were lost during follow-up） were divided into poor prognosis group（n=8） and clinical stabilization group（n=22）. The clinical data and laboratory examination indexes of the patients were collected. The percentages of CD4+inducible T-cell costimulatory factor （ICOS）+ chemokine C-X-C-motif receptor 5（CXCR5）+Tfh cells in the CD4+ T lymphocytes in peripheral blood of the patients in various groups（ percentages of Tfh cells ） were detected by flow cytometry. The relationships between the percentages of Tfh cells in peripheral blood of the patients in SLE with pregnancy group and the laboratory examination indexes were analyzed by Spearman correlation analysis.The levels of interleukin-6 （IL-6）， interleukin-21 （IL-21） and interferon-γ （IFN- γ） in peripheral blood of the subjects in various groups were detected by enzyme linked immunosorbent assay（ELISA）method. Results Compared with healthy pregnancy group， the percentage of Tfh cells in peripheral blood of the patients in SLE with pregnancy group was significantly increased（P<0.01）， and the percentage of Tfh cells in peripheral blood of the subjects in healthy non-pregnancy group was significantly decreased（P<0.05）. Compared with SLE without pregnancy group， the percentage of Tfh cells in peripheral blood of the patients in SLE with pregnancy group was significantly increased（P<0.05）. During the follow-up， compared with clinical stabilization group， the percentage of Tfh cells in peripheral blood of the patients in poor prognosis group was significantly increased（P<0.05）. The percentage of Tfh cells in peripheral blood of the patients in SLE with pregnancy group was positively correlated with the levels of anticardiolipin antibody （ACA） and anti-β2 glycoprotein Ⅰ（β2GPⅠ） antibody（r=0.743 1，P<0.05； r=0.830 7，P<0.01）. Compared with healthy pregnancy group， the levels of IL-6 and IL-21 in peripheral blood of the patients in SLE with pregnancy group were significantly increased（P<0.05）；compared with SLE without pregnancy group，the level of IL-21 in peripheral blood of the patients in SLE with pregnancy group was significantly increased（P<0.05）. Conclusion The increase of the percentage of Tfh cells in peripheral blood of the patients with SLE in early pregnancy may be related to the poor pregnancy prognosis in the patients with SLE.

Key words: Follicular helper T lymphocytes, Systemic lupus erythematosus, Pregnancy, Prognosis

中图分类号:

R593.24

白杨,杨晨曦,刘小强,刘羽,邢倩. 系统性红斑狼疮患者妊娠期外周血中滤泡辅助性T淋巴细胞的变化及其意义[J]. 吉林大学学报(医学版), 2023, 49(1): 166-172.

Yang BAI,Chenxi YANG,Xiaoqiang LIU,Yu LIU,Qian XING. Changes of follicular helper T lymphocytes in peripheral blood of patients with systemic lupus erythematosus during pregnancy and its significance[J]. Journal of Jilin University(Medicine Edition), 2023, 49(1): 166-172.

图/表 3

参考文献 26

1	WECKERLE C E， NIEWOLD T B. The unexplained female predominance of systemic lupus erythematosus： clues from genetic and cytokine studies［J］. Clin Rev Allergy Immunol， 2011， 40（1）： 42-49.
2	KATSUYAMA T， TSOKOS G C， MOULTON V R. Aberrant T cell signaling and subsets in systemic lupus erythematosus［J］. Front Immunol， 2018， 9： 1088.
3	LUAN X R， KANG X M， LI W P， et al. An investigation of the relationship between recurrent spontaneous abortion and memory T follicular helper cells［J］. Am J Reprod Immunol， 2017， 78（5）. DOI： 10.1111/aji.12714 . doi: 10.1111/aji.12714
4	CROTTY S. Follicular helper CD4 T cells （TFH）［J］. Annu Rev Immunol， 2011， 29： 621-663.
5	JIN X， CHEN J， WU J， et al. Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus［J］. Front Immunol， 2022， 13： 928359.
6	CROTTY S. T follicular helper cell differentiation， function， and roles in disease［J］. Immunity， 2014， 41（4）： 529-542.
7	MONTEIRO C， KASAHARA T M， CASTRO J R， et al. Pregnancy favors the expansion of circulating functional follicular helper T Cells［J］. J Reprod Immunol， 2017， 121： 1-10.
8	HEYDARLOU H， EGHABL-FARD S， AHMADI M， et al. Investigation of follicular helper T cells， as a novel player， in preeclampsia［J］. J Cell Biochem， 2019， 120（3）： 3845-3852.
9	ZHOU H Y， HU B L， HUANG N W， et al. Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus［J］. Clin Rheumatol， 2018， 37（9）： 2405-2413.
10	GLADMAN D D， IBAÑEZ D， UROWITZ M B. Systemic lupus erythematosus disease activity index 2000［J］. J Rheumatol， 2002， 29（2）： 288-291.
11	HOCHBERG M C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus［J］. Arthritis Rheum， 1997， 40（9）： 1725.
12	浦筱雯. 妊娠合并系统型红斑狼疮131例临床资料分析［D］. 上海：上海交通大学， 2008.
13	黄钟洲，肖雨，邹和建，等. 滤泡相关T细胞的特点及在系统性红斑狼疮中的研究进展［J］. 中华风湿病学杂志， 2021， 25（3）： 193-197.
14	PAYDAR K， NIAKAN KALHORI S R， AKBARIAN M，et al. A clinical decision support system for prediction of pregnancy outcome in pregnant women with systemic lupus erythematosus［J］. Int J Med Inform， 2017， 97： 239-246.
15	WANG W J， SUNG N， GILMAN-SACHS A， et al. T helper （Th） cell profiles in pregnancy and recurrent pregnancy losses： Th1/Th2/Th9/Th17/Th22/Tfh cells［J］. Front Immunol， 2020， 11： 2025.
16	王欣，张庆，罗帅寒天，等. 系统性红斑狼疮治疗靶点相关研究进展［J］. 中南大学学报（医学版）， 2021，46（11）： 1267-1275.
17	MEN K， CHEN Y， ZHANG J W， et al. The evaluation of cellular immune function in elderly patients with systemic lupus erythematosus［J］. Korean J Intern Med， 2019， 34（4）： 932-937.
18	冯秀南，袁艺，宿凯笙，等. 系统性红斑狼疮患者外周血T淋巴细胞亚群的分布及其与疾病活动和预后的关系［J］. 吉林大学学报（医学版）， 2019， 45（6）： 1415-1421.
19	RAO D A. T cells that help B cells in chronically inflamed tissues［J］. Front Immunol， 2018， 9： 1924.
20	COBB D A， KIM O K， GOLDEN-MASON L， et al. Hepatocyte-derived exosomes promote T follicular regulatory cell expansion during hepatitis C virus infection［J］. Hepatology， 2018， 67（1）： 71-85.
21	SHI W W， DONG L， SUN Q， et al. Follicular helper T cells promote the effector functions of CD8⁺ T cells via the provision of IL-21， which is downregulated due to PD-1/PD-L1-mediated suppression in colorectal cancer［J］. Exp Cell Res， 2018， 372（1）： 35-42.
22	JIN H， YANG K B， ZHANG H Y， et al. Expansion of circulating extrafollicular helper T-like cells in patients with chronic graft-versus-host disease［J］. J Autoimmun， 2019， 100： 95-104.
23	唐光俊，游晶，刘怀鄂，等. 辅助性T淋巴细胞17/调节性T淋巴细胞比值失衡在HBV相关肝脏疾病进展中的作用［J］. 临床肝胆病杂志， 2021，37（2）：414-418 .
24	FENG Y， YANG M， WU H J， et al. The pathological role of B cells in systemic lupus erythematosus： from basic research to clinical［J］.Autoimmunity，2020，53（2）： 56-64.
25	ZENG W H， LIU Z C， ZHANG S M， et al. Characterization of T follicular helper cells in allogeneic normal pregnancy and PDL1 blockage-induced abortion［J］. Sci Rep， 2016， 6： 36560.
26	HU C， LIU H L， PANG B， et al. Supraphysiological estradiol promotes human T follicular helper cell differentiation and favours humoural immunity during in vitro fertilization［J］. J Cell Mol Med， 2021， 25（14）： 6524-6534.

Group	n	Percentage of Tfh cells
SLE with pregnancy	32	1.47±0.35^**△
SLE without pregnancy	30	1.25±0.27
Healthy pregnancy	30	0.30±0.14
Healthy non-pregnancy	25	0.24±0.11^*

Group	n	IL-6	IL-21	IFN-γ
SLE with pregnancy	32	23.89±6.25^*	163.75±27.63^*△	117.49±18.27
SLE without pregnancy	30	19.43 ± 9.51	129.0 ± 21.15	113.47±14.76
Healthy pregnancy	30	9.72±6.76	71.56±31.37	92.03±17.13
Healthy non-pregnancy	25	10.15±5.47	67.91±21.39	84.69±8.76

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系统性红斑狼疮患者妊娠期外周血中滤泡辅助性T淋巴细胞的变化及其意义

Changes of follicular helper T lymphocytes in peripheral blood of patients with systemic lupus erythematosus during pregnancy and its significance

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