目的：探究血清白细胞介素-35(IL-35)、免疫球蛋白4/免疫球蛋白(IgG4/IgG)、促甲状腺免疫球蛋白(TSI)水平与甲状腺相关性眼病(TAO)活动度及病情严重程度的相关性分析。方法：前瞻性研究。选取2023年1月至2024年7月本院收治的TAO患者148例为观察组，根据TAO活动度分为活动组75例和非活动组73例，又根据病情严重程度分为重度组95例和轻度组53例； 另选取同期体检健康者148例为对照组。比较两组参与者血清中IL-35、IgG4/IgG、TSI水平； 分析血清IL-35、IgG4/IgG、TSI水平与TAO活动度及病情严重程度的相关性； 多因素Logistic回归分析影响TAO患者病情发展为重度的因素； ROC曲线分析血清IL-35、IgG4/IgG、TSI水平对TAO患者病情发展为重度的诊断价值。结果：与对照组相比，观察组患者血清IL-35水平明显降低，IgG4/IgG、TSI水平明显升高(均P<0.01)。与非活动组TAO患者相比，活动组患者血清IL-35水平明显降低，IgG4/IgG、TSI水平明显升高(均P<0.01)； 与轻度组相比，重度组患者血清IL-35水平明显降低，病程、IgG4/IgG、TSI水平明显升高(均P<0.01)。血清IL-35水平与TAO活动度及病情严重程度呈负相关(r=-0.529、-0.554，均P<0.01)，血清IgG4/IgG水平与TAO活动度及病情严重程度呈正相关(r=0.625、0.663，均P<0.01)，血清TSI水平与TAO活动度及病情严重程度呈正相关(r=0.594、0.607，均P<0.01)。多因素Logistic回归分析结果显示，血清IL-35、IgG4/IgG、TSI水平均是影响TAO患者病情发展为重度的因素(均P<0.01)。血清IL-35、IgG4/IgG、TSI水平诊断TAO患者病情发展为重度的曲线下面积(AUC)分别为0.868、0.859、0.830，三者联合诊断的AUC为0.955，明显高于各单一指标诊断(Z三者联合-IL-35=2.893、Z三者联合-IL-35=3.510、Z三者联合-IL-35=4.157，P=0.004、<0.01、<0.01)。结论：TAO患者血清IL-35水平明显下调，IgG4/IgG、TSI水平明显上调，且IL-35、IgG4/IgG、TSI水平与TAO活动性及病情严重程度相关，三者联合对TAO患者病情发展为重度具有较高的诊断价值。

AIM: To investigate the correlation of serum interleukin-35(IL-35), immunoglobulin 4/immunoglobulin(IgG4/IgG), thyroid stimulating immunoglobulin(TSI)levels with the activity and severity of thyroid associated ophthalmopathy(TAO).METHODS:Prospective study. A total of 148 TAO patients admitted to our hospital from January 2023 to July 2024 were selected as the observation group. They were assigned into an active group(75 cases)and an inactive group(73 cases)based on their activity level, and were assigned into a severe group(95 cases)and a mild group(53 cases)based on the severity of their condition; another 148 healthy patients who underwent physical examinations were regarded as the control group. The levels of IL-35, IgG4/IgG, and TSI in serum were compared between the two groups. The correlation between serum IL-35, IgG4/IgG, and TSI levels and TAO activity and severity of illness were analyzed. A multivariate Logistic regression was performed to analyze the influencing factors of TAO patients developing severe symptoms. ROC curve was applied to analyze the diagnostic value of serum IL-35, IgG4/IgG, and TSI levels for the development of severe TAO in patients.RESULTS: Compared with the control group, the serum IL-35 level in the observation group was significantly lower, while IgG4/IgG and TSI levels were significantly higher(all P<0.01). Compared with non-active TAO patients, active TAO patients had significantly lower serum IL-35 level and significantly higher IgG4/IgG and TSI levels(all P<0.01). Compared with the mild TAO patients, severe TAO patients had significantly lower serum IL-35 level and significantly higher disease duration, IgG4/IgG, and TSI levels(all P<0.01). The serum IL-35 level was negatively correlated with TAO activity and disease severity(r=-0.529, -0.554, both P<0.01), while serum IgG4/IgG level was positively correlated with TAO activity and disease severity(r=0.625, 0.663, both P<0.01). Serum TSI levels were positively correlated with TAO activity and disease severity(r=0.594, 0.607, both P<0.01). Multivariate Logistic regression analysis showed that serum IL-35, IgG4/IgG, and TSI levels were all factors influencing the progression of TAO patients to severe disease(all P<0.01). The areas under the curve(AUC)for diagnosing the progression of TAO patients to severe disease using serum IL-35, IgG4/IgG, and TSI levels were 0.868, 0.859, and 0.830, respectively. The combined AUC for the three markers was 0.955, significantly higher than that of each individual marker(Zthree factors combination-IL-35=2.893, Zthree factors combination-IL-35=3.510, Zthree factors combination-IL-35=4.157, P=0.004, <0.01, <0.01).CONCLUSION: Serum IL-35 level is significantly downregulated in TAO patients, while IgG4/IgG and TSI levels are significantly upregulated. The levels of IL-35, IgG4/IgG, and TSI are correlated with the activity and severity of TAO, and their combination has high diagnostic value for TAO developing into severe.

四川省科学技术厅项目(No.2025JDKP0174)