抗组织转谷氨酰胺酶IgA抗体滴度和HLA-DQ分型在1型糖尿病合并乳糜泻诊断中作用

Role of anti-tissue transglutaminase IgA antibody titer and HLA-DQ typing in the diagnosis of type 1 diabetes mellitus with celiac disease

目的探讨抗组织转谷氨酰胺酶IgA(IgA-抗tTG)抗体滴度以及人类白细胞抗原(HLA)-DQ分型对1型糖尿病(T1DM)合并乳糜泻(CD)发生的预测价值。方法选取2019年11月到2023年11月在内分泌科就诊的所有<18岁的T1DM患儿和同期体检的健康儿童作为研究对象,进行相关血清学分析及CD相关的HLA等位基因(DQ 2、DQ 8)检测。IgA-抗tTG抗体阳性患儿均行十二指肠病理活检。分析IgA-抗tTG滴度和Marsh分期之间相关性,采用ROC曲线评价IgA-抗tTG预测CD的诊断价值。结果纳入577例T1DM患儿,其中女性314例(54.4%),中位年龄10.0(5.0~16.0)岁。对照组150例,女性72例(48.0%),中位年龄9.5(6.0~17.0)岁。T1DM患儿中77例(13.3%)IgA-抗tTG抗体反应呈阳性(>18 IU/L),其中60例(77.6%)十二指肠组织病理学检查阳性,Marsh 2期19例,Marsh 3a期4例,Marsh 3 b期18例,Marsh 3 c期19例,均诊断为CD;余17例十二指肠组织病理学检查阴性,经过其他检查最终被确诊为小麦过敏或麸质敏感。46例IgA-抗tTG抗体阴性但仍存在谷胶依赖症状的T1DM组患儿也进行十二指肠病理活检,其中21例病理结果符合Marsh 2期或3期,同样诊断为CD。总计81例T1DM患儿确诊为合并CD。Spearman相关性分析显示81例T1DM合并CD患儿的IgA-抗tTG抗体水平与其Marsh分期之间呈显著正相关(r_(s)=0.76,P<0.001)。IgA-抗tTG抗体滴度预测CD阳性的ROC曲线下面积(AUC)为0.83(95%CI:0.72~0.93);IgA-抗tTG抗体滴度最佳截断值为87.65 IU/L,其预测CD的灵敏度为83.19%,特异度为92.20%。对照组血清IgA-抗tTG抗体反应均阴性。有CD与无CD的T1DM组之间HLA-DQ分型分布差异无统计学意义(P>0.05)。结论IgA-抗tTG抗体滴度在T1DM患儿合并CD诊断中具有一定价值,HLA基因分型可能作为血清抗体检测结果的辅助筛查手段。

Objective To investigate the predictive value of anti-tissue transglutaminase IgA(IgA-anti-tTG)antibody titers and human leukocyte antigen(HLA)-DQ typing in the occurrence of type 1 diabetes mellitus(T 1 DM)associated with celiac disease(CD).Methods All T 1 DM children<18 years old who visited the endocrinology department from November 2019 to November 2023 and healthy children who underwent physical examination during the same period were selected as the study objects.All participants underwent serological analysis and detection of CD-related HLA alleles(DQ 2 and DQ 8).All children with positive IgA-anti-tTG antibody underwent duodenal pathological biopsy(Marsh grade).The correlation between IgA-anti-tTG titer and Marsh classification was analyzed.ROC curve was used to evaluate the diagnostic value of IgA-anti-tTG in predicting CD.Results A total of 577 patients with T 1 DM were enrolled,of whom 314(54.4%)were females with a median age of 10.0(5.0 to 16.0)years.The control group consisted of 150 patients,including 72 females(48.0%),with a median age of 9.5(6.0 to 17.0)years.In the T 1 DM group,77 patients(13.3%)had a positive IgA-anti-tTG antibody response(>18 IU/L),of whom 60(77.6%)had positive duodenal histopathology.Nineteen children were in Marsh 2 stage,4 were in Marsh 3 a stage,18 were in Marsh 3 b stage,19 were in Marsh 3 c stage,and all of whom were diagnosed with CD.The remaining 17 patients had negative duodenal histopathology,and after other tests,they were finally diagnosed with wheat allergy or gluten sensitivity.Duodenal pathological biopsy was also performed in 46 children in the T 1 DM group who were negative for IgA-anti-tTG antibody but still had glut-dependent symptoms.Among them,21 patients were found to be Marsh stage 2 or 3 and were also diagnosed as CD.Finally,a total of 81 children were identified as having T 1 DM combined with CD.Spearman correlation analysis showed a significant positive correlation between IgA-antitTG antibody level and Marsh stage in 81 children with T1DM and CD(r_(s)=0.76,P<0.001).The area under ROC curve(AUC)of IgA-anti-tTG antibody titers predicting CD-positive was 0.83(95%CI:0.72-0.93).The optimal cutoff threshold for IgA-anti-tTG antibody titer was 87.65 IU/L,and its sensitivity and specificity for predicting CD were 83.19%and 92.20%.The serum IgA-anti-tTG antibody reaction in the control group was negative.There was no significant difference in HLADQ typing distribution between T 1 DM group with CD and without CD(P>0.05).Conclusions The titer of IgA-anti-tTG antibody has a certain value in the diagnosis of T 1 DM children complicated with CD,and HLA typing may be an auxiliary screening method for serum antibody detection results.