The Evaluation Value of Treg Cells，Th17 Cells and Treg / Th17 Levels in Viral Myocarditis and Disease
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摘要:
目的 分析调节性T细胞（Treg）、辅助性T细胞（Th17）、Treg / Th17变化对病毒性心肌炎（viral myocarditis，VMC）患者发病及病情严重程度的评估价值，进一步分析VMC患者发病及病情严重程度的影响因素。 方法 按1∶1匹配原则筛选研究对象，选取定州市人民医院2022年1月至2024年1月期间收治的140例VMC患者作为观察组，依据患者左心室射血分数（left ventricular ejection fraction，LVEF）和血清肌钙蛋白（cardiac troponin Ⅰ，cTnI）水平判定病情严重程度，根据病情严重程度将观察组分为轻症组（n = 79）和中重症组（n = 61）；另将定州市人民医院同期体检健康者140名作为对照组；所有患者随访1年，据受试者工作特征（ROC）中Treg / Th17截断值将患者根据指标表达高低分组分为Treg / Th17高表达组107例、Treg / Th17低表达组30例。对比对照组和观察组Treg、Th17、Treg / Th17水平与基线资料；对比轻症组和中重症组Treg、Th17、Treg / Th17水平与基线资料；采用ROC曲线分析Treg、Th17、Treg / Th17单独及通过并联模式的联合检测对VMC患者发病及病情严重程度的诊断价值；多因素Logistic回归分析VMC患者发病及病情严重程度的影响因素。 结果 观察组研究期间脱落4例，纳入136例，对照组脱落3例，纳入137例。与对照组比较，观察组Treg、Treg / Th17明显更低，Th17明显更高（P < 0.05）；Th17是影响VMC患者发病的危险因素（OR = 2.547、2.698），Treg、Treg / Th17是影响VMC患者发病的保护因素（OR = 0.507、0.519），Treg、Th17、Treg / Th17联合检测VMC患者发病的诊断曲线下面积敏感度、特异度均高于单独检测，Delong检验证实联合检测的AUC（0.893）显著大于Treg（0.664，Z = 7.042）、Th17（0.696，Z = 6.033）及Treg / Th17（0.721，Z = 5.691）单一检测（P < 0.05）；与轻症组比较，中重症组Treg、Treg / Th17明显更低，Th17明显更高（P < 0.05）；Treg、Treg / Th17为影响VMC患者病情严重程度的独立保护因素（OR = 0.547、0.419），Th17为影响VMC患者病情严重程度的独立危险因素（OR = 2.554）（P < 0.05）；Treg、Th17、Treg / Th17联合检测VMC患者病情严重程度的AUC、敏感度、特异度均高于单独检测（P < 0.05）；随访1年VMC患者共死亡36例，Treg / Th17高表达患者1年生存率及OS高于Treg / Th17低表达患者（P < 0.05）。 结论 VMC患者发病及病情进展过程中均存在Treg / Th17细胞因子失衡，Treg / Th17可作为尽早察觉VMC患者病情恶化的重要指标，临床可将Treg、Th17、Treg / Th17联合检测方案作为临床评估VMC患者发病诊断及病情发展的参考依据。 -
关键词:
- Treg / Th17 /
- 病毒性心肌炎 /
- 疾病进展 /
- 诊断 /
- 影响因素
Abstract:Objective To analyze the evaluation value of regulatory T cells （Treg）, helper T cells （Th17） and Treg / Th17 changes on the morbidity and severity of viral myocarditis （VMC） patients, and further analyze the influencing factors of morbidity and severity of VMC patients. Methods Press 1∶1 The research objects were screened according to the matching principle. 140 VMC patients admitted to Dingzhou People’ s Hospital from January 2022 to January 2024 were selected as the observation group, and the severity of the disease was determined according to the left ventricular ejection fraction （LVEF） and serum troponin （cTnI） levels. According to the severity of the disease, the observation group was divided into a mild group （n = 79） and a moderately severe group （n = 61）. In addition, 140 healthy people in the same period were selected as the control group. All patients were followed up for one year. According to the Treg / Th17 cutoff value in the receiver operating characteristic （ROC） curve, the patients were grouped based on the expression levels of the indicators into the Treg / Th17 high-expression group （107 patients） and the Treg / Th17 low-expression group （30 patients）. The levels of Treg, Th17, Treg / Th17 and baseline data were compared between the control group and the observation group. The levels of Treg, Th17, Treg / Th17 and baseline data were compared between the mild group and the moderate-severe group. The diagnostic value of the combined detection of Treg, Th17, Treg / Th17 alone and in a parallel mode for the onset and severity of the disease in patients with VMC was analyzed using the ROC curve. Multivariate Logistic regression was used to analyze the influencing factors of the onset and severity of VMC. Results During the study period, 4 cases were shed in the observation group, including the study period, 4 cases dropped out and 136 cases were included in the observation group, and 3 cases dropped out and 137 cases were included in the control group. Compared with the control group, Treg and Treg / Th17 in the observation group were significantly lower, and Th17 was significantly higher （P < 0.05）. Th17 was the risk factor affecting the incidence of VMC patients （OR = 2.547, 2.698）, Treg and Treg / Th17 were the protective factors affecting the incidence of VMC patients （OR = 0.507, 0.519）. The area under the curve （AUC）, sensitivity and specificity of Treg, Th17 and Treg / Th17 combination in the diagnosis of VMC were higher than those of single detection. Delong’ s test confirmed that the AUC of the combined detection （0.893） was significantly greater than that of the individual detections of Treg （0.664, Z = 7.042）, Th17 （0.696, Z = 6.033）, and Treg / Th17 （0.721, Z = 5.691） （P < 0.05）. Compared with the mild group, Treg and Treg / Th17 in the moderate and severe group were significantly lower, and Th17 was significantly higher （P < 0.05）. Treg and Treg / Th17 were the independent protective factors affecting the severity of VMC patients （OR = 0.547, 0.419）, and Th17 was the independent risk factor affecting the severity of VMC patients （OR = 2.554） （P < 0.05）. The AUC, sensitivity and specificity of Treg, Th17 and Treg / Th17 combination in detecting the severity of VMC patients were higher than those of single detection （P < 0.05）. During the 1-year follow-up, a total of 36 patients with VMC died. The 1-year survival rate and OS of patients with high expression of Treg / Th17 were higher than those of patients with low expression of Treg / Th17 （P < 0.05）. Conclusion During the onset and progression of VMC, there is an imbalance in Treg / Th17 cytokines. Treg / Th17 can serve as an important indicator for detecting the deterioration of the condition in VMC patients at an early stage. Clinically, the combined detection scheme of Treg, Th17, and Treg / Th17 can be used as a reference for clinical assessment of the onset diagnosis and disease progression of VMC patients. -
Key words:
- Treg / Th17 /
- Viral myocarditis /
- Disease progression /
- Diagnosis /
- Influencing factor
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图 1 Treg、Th17、Treg / Th17单独及联合检测对VMC患者发病的诊断ROC曲线
Figure 1. ROC curve for the diagnosis of VMC patients based on the individual and combined detection of Treg，Th17，and Treg / Th17
图 2 Treg、Th17、Treg / Th17单独及联合检测对VMC患者病情严重程度的评估ROC曲线
Figure 2. ROC curves for evaluating the severity of VMC patients’ conditions by detecting Treg，Th17，Treg / Th17 alone and in combination
表 1 对照组和观察组Treg、Th17、Treg / Th17水平比较（$\bar x \pm s $）
Table 1. Comparison of Treg，Th17 and Treg / Th17 levels between the control group and the observation group （$\bar x \pm s $）
组别 Treg（%） Th17（%） Treg / Th17 对照组（n = 137） 6.56 ± 0.39 1.37 ± 0.24 4.51 ± 0.69 观察组（n = 136） 5.69 ± 0.93 1.85 ± 0.44 3.26 ± 0.82 t 10.027 11.206 13.524 P < 0.001* < 0.001* < 0.001* *P < 0.001。 
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表 2 对比对照组、观察组的基线资料差异[（$\bar x \pm s $）/n（%）]
Table 2. Comparison of baseline data differences between the control group and the observation group [（$\bar x \pm s $）/ n（%）]
因素 对照组（n = 137） 观察组（n = 136） t/χ2 P 年龄（岁） 44.55 ± 3.42 44.61 ± 3.57 −0.142 0.887 男性 75（54.74） 77（56.62） −0.332 0.740 BMI（kg/m2） 23.80 ± 0.95 23.69 ± 1.03 0.917 0.360 文化程度 高中及以下 91（66.42） 90（66.18） 0.002 0.966 大专及以上 45（58.97） 45（55.17） 葡萄球菌属阳性 9（6.57） 17（12.50） 2.786 0.095 链球菌属阳性 6（4.38） 14（10.29） 3.517 0.061 肠球菌属阳性 6（4.38） 13（9.56） 2.827 0.093 大肠埃希细菌阳性 9（6.57） 16（11.76） 2.214 0.137 肺炎克雷伯菌阳性 10（7.30） 19（13.97） 3.199 0.074
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表 3 变量赋值表
Table 3. Variable assignment table
因素 变量名 赋值 Treg X1 原值录入 Th17 X2 原值录入 Treg / Th17 X3 原值录入 VMC发病 Y 对照组 = 0，观察组 = 1
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表 4 VMC患者发病的多因素Logistic回归分析
Table 4. Multivariate logistic regression analysis of the incidence of VMC patients
影响因素 B SE Wald P OR 95%CI Treg −0.204 0.412 9.865 < 0.001* 0.507 0.339～0.798 Th17 1.987 0.293 9.925 < 0.001* 2.547 1.392～5.174 Treg / Th17 −0.254 0.274 8.214 < 0.001* 0.519 0.172～0.616 *P < 0.05。
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表 5 Treg、Th17、Treg / Th17单独及联合试验对VMC患者发病的诊断价值
Table 5. Diagnostic value of Treg，Th17，Treg / Th17 alone and in combination tests for the onset of VMC patients
指标 95%CI AUC 敏感度（%） 特异度（%） 截断值 约登指数 Treg 0.605～0.720 0.664 72.79（99/136） 63.50（87/137） < 6.11 0.363 Th17 0.637～0.750 0.696 63.97（87/136） 71.53（98/137） > 1.53 0.355 Treg / Th17 0.664～0.774 0.721 75.00（102/136） 66.42（91/137） < 3.90 0.414 联合试验 0.851～0.927 0.893 88.97（121/136） 89.05（122/137） − 0.780 Z（χ2）/PTreg～联合试验 − 7.042/ < 0.001 11.508/0.001 24.707/ < 0.001 − − Z（χ2）/PTh17～联合试验 − 6.033/ < 0.001 23.620/ < 0.001 13.285/ < 0.001 − − Z（χ2）/PTreg / Th17～联合试验 − 5.691/ < 0.001 8.986/0.003 20.266/ < 0.001 − −
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表 6 比较轻症组、中重症组VMC患者临床资料[（$\bar x \pm s $）/n（%）]
Table 6. Comparison of clinical data differences between mild case group and severe-moderate case group of VMC patients [（$\bar x \pm s $）/ n（%）]
因素 轻症组（n = 78） 中重症组（n = 58） t/χ2 P 年龄（岁） 45.28 ± 3.84 44.47 ± 4.07 1.185 0.238 男性 46（58.97） 31（53.45） 0.414 0.520 BMI（kg/m2） 23.61 ± 1.04 23.78 ± 1.05 0.936 0.351 文化程度 0.197 0.657 高中及以下 32（41.03） 26（44.83） 大专及以上 46（58.97） 32（55.17） 葡萄球菌属阳性 7（8.97） 10（17.24） 2.079 0.149 链球菌属阳性 6（7.69） 8（13.79） 1.341 0.247 肠球菌属阳性 5（6.41） 8（13.79） 2.097 0.148 大肠埃希细菌阳性 7（8.97） 9（15.52） 1.372 0.241 肺炎克雷伯菌阳性 8（10.26） 11（18.97） 2.099 0.147 NT-proBNP（ng/L） 4362.23 ± 69.164353.63 ± 68.670.720 0.473 Treg（%） 5.99 ± 0.97 5.30 ± 0.68 4.869 < 0.001* Th17（%） 1.69 ± 0.36 2.06 ± 0.45 5.084 < 0.001* Treg / Th17 3.60 ± 0.77 2.81 ± 0.65 6.463 < 0.001* *P < 0.001。
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表 7 变量赋值表
Table 7. Variable assignment table
因素 变量名 赋值 Treg X1 原值录入 Th17 X2 原值录入 Treg / Th17 X3 原值录入 疾病进展 Y 轻症 = 0，中重症 = 1
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表 8 VMC患者病情严重程度影响因素的多因素Logistic回归分析
Table 8. Multivariate Logistic regression analysis of factors affecting the severity of disease in VMC patients
影响因素 B SE Wald P OR 95%CI Treg −0.224 0.312 9.665 < 0.001* 0.547 0.239～0.798 Th17 1.286 0.296 10.825 < 0.001* 2.554 1.394～5.174 Treg / Th17 −0.354 0.284 8.224 < 0.001* 0.419 0.152～0.816 *P < 0.05。
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表 9 Treg、Th17、Treg / Th17单独及联合检测对VMC患者病情严重程度的评估价值
Table 9. Evaluation value of Treg，Th17，Treg / Th17 individual and vombined detection for the severity of disease in VMC patients
指标 95%CI AUC 敏感度（%） 特异度（%） 截断值 约登指数 Treg 0.530～0.699 0.617 69.00（40/58） 53.80（41/78） ≤ 6.08 0.228 Th17 0.553～0.720 0.640 32.05（19/58） 96.55（75/78） ≤ 1.3 0.286 Treg / Th17 0.565～0.731 0.651 79.50（46/58） 48.30（37/78） > 2.97 0.278 联合试验 0.741～0.877 0.816 100.00（58/58） 57.70（45/78） − 0.577 Z（χ2）/PTreg～联合试验 − 3.510/ < 0.001 21.306/ < 0.001 0.415/0.520 − − Z（χ2）/PTh17～联合试验 − 2.887/0.004 58.753/ < 0.001 32.500/ < 0.001 − − Z（χ2）/PTreg / Th17～联合试验 − 2.684/0.007 13.385/ < 0.001 1.645/0.200 − −
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表 10 比较PTEN、MMR不同情况与IDC患者预后的关系[（$\bar x \pm s $）/ n（%）]
Table 10. compares the relationship between PTEN and MMR variations and the prognosis of IDC patients [（$\bar x \pm s $）/ n（%）]
指标 生存率 OS（月） Treg / Th17高表达（n = 107） 95（88.79） 11.73 ± 0.84 Treg / Th17低表达（n = 30） 6（20.00） 10.93 ± 1.53 t（χ2） 57.226 3.742 P < 0.001* < 0.001* *P < 0.001。
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