血清TRAb IgG亚型在甲状腺相关性眼病患者中的特征及临床意义

The characteristics and clinical significance of serum TRAb IgG subtype in patients with thyroid associated ophthalmopathy

目的探讨血清TRAb IgG各亚型在不同活动分期甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者中的分布特点,及其在评估TAO活动度中的价值。方法选取2018年8月至2019年2月郑州大学第一附属医院收治的TAO患者43例,依据临床活动度评分(clinical activity score,CAS)进一步分为活动期组(AP组,CAS≥3分,22例)和静止期组(IP组,CAS<3分,21例);Graves病患者(GD组)30例,桥本甲状腺炎患者(HT组)19例,并以同期健康体检者(NC组)50名作为正常对照。收集各组受试者临床基本资料,化学发光免疫法检测血清FT3、FT4、TSH、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)、促甲状腺激素受体抗体(TRAb)水平,酶联免疫吸附法检测血清TRAb IgG和IgG各亚型的百分结合率[binding rate in percentage,(B)],比较各亚型的阳性率和阳性亚型的相对含量。结果(1)与HT组相比,TAO组、GD组IgG1、IgG2阳性率降低,差异有统计学意义(P<0.05)。各疾病组间TRAb IgG亚型相对含量无明显差异(P>0.05)。(2)与IP组相比,AP组IgG1(B)、IgG1阳性率显著升高,IgG4(B)、IgG4相对含量显著降低(P<0.05)。(3)IgG1(B)与TAO活动度呈正相关(B=6.190,P=0.007),IgG4(B)越高越倾向于静止期,但差异无统计学意义(B=-16.390,P=0.052)。(4)活动率评估TAO处于活动期的受试者工作特征(ROC)曲线下面积为0.859(95%CI 0.746~0.973,P<0.05),当活动率为4.29时,约登指数最大,其判断敏感度为81.8%,特异度为81.0%。结论在TAO患者中血清TRAb IgG1水平升高提示疾病趋向活动期,IgG4水平升高提示疾病趋向静止期。活动率可为评估TAO是否处于活动期提供参考依据。

Objective To explore the distribution of serum TRAb IgG subtypes in patients with thyroid-associated ophthalmopathy(TAO)at different stages and its value in assessing TAO activity.Methods Forty-three patients with TAO,30 patients with Graves′disease(GD group),19 patients with Hashimoto′s thyroiditis(HT group),and 50 healthy subjects(NC group)admitted to the First Affiliated Hospital of Zhengzhou University were collected from August 2018 to February 2019.According to the clinical activity score(CAS),the patients with TAO were further divided into the active period group(AP group,CAS≥3 points,22 cases)and the inactive period group(IP group,CAS<3 points,21 cases).The basic clinical data of subjects in each group were collected.The serum concentrations of FT3,FT4,TSH,thyroperoxidase antibody(TPOAb),thyroglobulin antibody(TgAb),and thyroid-stimulating hormone receptor antibody(TRAb)were detected by chemiluminescence immunoassay and the binding rate in percentage(B)of serum TRAb IgG and IgG subtypes were detected by ELISA.The positive rate in each group and relative content of positive samples were compared.Results(1)Compared with HT group,the positive rates of IgG1 and IgG2 in TAO group and GD group were significantly decreased(P<0.05).There was no significant difference in the relative content of positive TRAb IgG subtype among these disease groups(P>0.05).(2)Compared with the IP group,IgG1(B)and the positive rates of IgG1 in the AP group were increased while IgG4(B)and the relative contents of IgG4 were reduced(P<0.05).(3)IgG1(B)was positively correlated with TAO activity(B=6.190,P=0.007),and higher IgG4(B)indicated more inclinations to the inactive period(B=-16.390,P=0.052).(4)The area under the curve of receiver operating characteristic(ROC)for TAO developing into active period assessed by activity rate was 0.859(95%CI 0.746-0.973,P<0.05).When the activity rate was 4.29,the Jordon index showed the largest,with sensitivity of 81.8%and specificity of 81.0%.Conclusions Elevated levels of TRAb IgG1 in the patients with TAO indicate a tendency to active period,while elevated levels of TRAb IgG4 indicate a tendency to inactive period.The activity rate can provide a reference for assessing whether TAO is active or not.