血清细胞毒性T淋巴细胞相关蛋白4和高迁移率族蛋白B1对不明原因复发性流产的评估价值

doi:10.3969/j.issn.1006-5725.2025.16.017

摘要/Abstract

摘要：

目的探讨血清细胞毒性T淋巴细胞相关蛋白4（CTLA4）、高迁移率族蛋白B1（HMGB1）与辅助性T细胞17（Th17）/调节性T细胞（Treg）平衡的相关性，并研究其对不明原因复发性流产（URSA）的评估价值。方法选取2022年9月至2024年9月医院收治的URSA患者102例作为URSA组，另选取同期于医院产检的健康孕妇80例作为健康组。检测两组血清CTLA4、HMGB1水平，检测两组Th17及Treg水平，并计算Th17/Treg，收集记录两组一般资料。采用Pearson分析血清CLTA4、HMGB1水平与Th17、Treg、Th17/Treg的相关性。采用logistic回归分析URSA发生的影响因素。采用受试者工作特征（ROC）曲线分析血清CTLA4、HMGB1水平评估URSA发生的价值。结果 URSA组血清CTLA4水平低于健康组，HMGB1水平高于健康组，Th17水平、Th17/Treg高于健康组，Treg水平低于健康组（P < 0.05）。血清CTLA4水平与Th17水平、Th17/Treg呈负相关，与Treg水平呈正相关（P < 0.05）。HMGB1水平与Th17水平、Th17/Treg呈正相关，与Treg水平呈负相关（P < 0.05）。孕次、血清CTLA4水平、血清HMGB1水平、Th17水平、Treg水平、Th17/Treg是URSA发生的独立影响因素（P < 0.05）。血清CTLA4、HMGB1水平及两种指标联合评估URSA的曲线下面积（AUC）分别为0.841、0.787、0.908，约登指数分别为0.652、0.491、0.656。结论 URSA患者血清CTLA4水平降低、HMGB1水平升高，与Th17/Treg平衡改变相关，血清CTLA4、HMGB1水平对URSA具有辅助评估价值。

Abstract:

Objective To investigate the correlation between serum cytotoxic T lymphocyte associated protein 4 （CTLA4）， high mobility group box 1 （HMGB1） and the balance of helper T cell 17 （Th17）/regulatory T cell （Treg）， and to study their diagnostic significance for unexplained recurrent spontaneous abortion （URSA）. Methods A total of 102 patients with URSA admitted to the hospital from September 2022 to September 2024 were selected as the URSA group， and another 80 healthy pregnant women who underwent prenatal examinations in the hospital during the same period were selected as the healthy group. The levels of serum CTLA4 and HMGB1 in the two groups were detected， the levels of Th17 and Treg in the two groups were detected， the Th17/Treg ratio was calculated， and the general data of the two groups were collected and recorded. Pearson was used to analyze the correlations between the levels of serum CLTA4 and HMGB1 and Th17， Treg， and Th17/Treg. logistic regression was used to analyze the influencing factors of URSA occurrence. The receiver operating characteristic （ROC） curve was used to analyze the value of serum CTLA4 and HMGB1 levels in evaluating the occurrence of URSA. Results the serum CTLA4 level in the URSA group was lower than that in the healthy group， the HMGB1 level was higher than that in the healthy group， the Th17 level and Th17/Treg were higher than those in the healthy group， and the Treg level was lower than that in the healthy group （P < 0.05）. The serum CTLA4 level was negatively correlated with the Th17 level and Th17/Treg， and positively correlated with the Treg level （P < 0.05）. The level of HMGB1 was positively correlated with the level of Th17 and Th17/Treg， and negatively correlated with the level of Treg （P < 0.05）. Pregnancy frequency， serum CTLA4 level， serum HMGB1 level， Th17 level， Treg level， and Th17/Treg are independent influencing factors for the occurrence of URSA （P < 0.05）. The areas under the curve （AUC） of serum CTLA4 and HMGB1 levels and the combined evaluation of URSA by the two indicators were 0.841， 0.787， and 0.908 respectively， and the Youden indices were 0.652， 0.491， and 0.656 respectively. Conclusions The serum CTLA4 level is decreased and the HMGB1 level is increased in patients with URSA， which is related to the change of Th17/Treg balance. The levels of serum CTLA4 and HMGB1 have auxiliary diagnostic significance for URSA.

Key words: cytotoxic T lymphocyte associated protein 4, high mobility group box 1, helper T cell 17/ regulatory T cell, unexplained recurrent spontaneous abortion

中图分类号:

R711.6

邵丹卉,徐杨,韩秋峪,孙礼强. 血清细胞毒性T淋巴细胞相关蛋白4和高迁移率族蛋白B1对不明原因复发性流产的评估价值[J]. 实用医学杂志, 2025, 41(16): 2556-2560.

Danhui SHAO,Yang XU,Qiuyu HAN,Liqiang. SUN. Study on the evaluation value of serum CTLA4 and HMGB1 for unexplained recurrent spontaneous abortion[J]. The Journal of Practical Medicine, 2025, 41(16): 2556-2560.

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项目	健康组（n = 80）	URSA组（n = 102）	t/χ² 值	P值
年龄/岁	27.64 ± 5.21	28.19 ± 5.46	0.688	0.492
BMI/（kg/m²）	23.78 ± 3.43	23.52 ± 3.17	0.530	0.597
孕周/周	7.22 ± 1.13	7.34 ± 1.21	0.684	0.495
孕次/[例（%）]			29.994	< 0.001
> 3次	11（13.75）	54（52.94）
≤ 3次	69（86.25）	48（47.06）
吸烟史/[例（%）]			0.268	0.604
是	17（21.25）	25（24.51）
否	63（78.75）	77（75.49）
饮酒史/[例（%）]			0.531	0.466
是	31（38.75）	45（44.12）
否	49（61.25）	57（55.88）

组别	例数	CTLA4	HMGB1
健康组	80	13.45 ± 4.93	70.15 ± 10.84
URSA组	102	8.15 ± 2.00	82.85 ± 11.25
t值		9.876	7.681
P值		< 0.001	< 0.001

组别	例数	Th17/%	Treg/%	Th17/Treg
健康组	80	1.68 ± 0.43	4.62 ± 0.72	0.37 ± 0.13
URSA组	102	2.45 ± 0.69	3.68 ± 0.74	0.69 ± 0.17
t值		8.736	8.607	13.938
P值		< 0.001	< 0.001	< 0.001

指标	CTLA4		HMGB1
指标	r值	P值	r值	P值
Th17	-0.423	< 0.001	0.402	< 0.001
Treg	0.371	< 0.001	-0.353	< 0.001
Th17/Treg	-0.547	< 0.001	0.514	< 0.001

因素	β	SE	Wald χ²	P值	OR值（95%CI）
孕次	0.322	0.114	7.978	0.005	1.380（1.104 ~ 1.725）
CTLA4	-0.175	0.063	7.716	0.006	0.839（0.742 ~ 0.950）
HMGB1	0.166	0.068	5.959	0.015	1.181（1.033 ~ 1.349）
Th17	0.173	0.065	7.084	0.008	1.189（1.047 ~ 1.350）
Treg	-0.269	0.103	6.821	0.009	0.764（0.624 ~ 0.935）
Th17/Treg	0.179	0.058	9.525	0.006	1.196（1.068 ~ 1.340）