T1DM患者直系亲属ZnT-8A、IA-2A、IAA、GADA、ICA检测及3年发病风险分析

目的探讨1型糖尿病(T1DM)患者直系亲属Zn T-8A、IA-2A、IAA、GADA、ICA检测及3年发病风险的临床价值。方法采用放射免疫沉淀法检测T1DM患者(n=80)及其直系亲属(n=100)与正常受试者(n=100)血清中锌转运蛋白8抗体(Zn T-8A)阳性率,同时采用免疫印迹试剂法检测胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶自身抗体(IA-2A)、胰岛素自身抗体(IAA),对不同组合抗体联合检测效果用ROC曲线评价,同时分析直系亲属中3年发病情况。结果 T1DM组患者Zn T-8A、IA-2A、IAA、GADA、ICA血清抗体检出率均显著高于直系亲属组和健康组(P0.05),且直系亲属组上述血清抗体检出率显著高于健康组(P0.05)。5种抗体联合检测总阳性率最高为91.25%,其中2种、3种和4种抗体联合总阳性率最高,分别为83.75%、87.5%和90.0%。5种抗体联合检测法的ROC曲线下面积(AUC)最大,各种抗体联合检测法AUC无显著差异,但均显著高于Zn T-8A抗体单独检测(P0.05)。3年随访调查中2例Zn T-8A和GADA抗体阳性直系亲属被诊断为T1DM,其余个体在随访期间无发病症状。结论 5种抗体联合检测能够提高T1DM临床诊断率,其中Zn T-8A和GADA抗体组合检测,对糖尿病及时、准确分型具有重要价值,还可作为T1DM直系亲属流行病学的筛选指标。

Detection of ZnT-8A,IA-2A,IAA, GADA and ICA and 3-year onset risk of direct relatives of patients with type 1 diabetes mellitus

Objective To investigate the clinical value of detection of ZnT-8A,IA-2A,IAA,GADA and ICA and 3-year onset risk in direct relatives of patients with type 1 diabetes mellitus (T1DM).Methods The positive rates of serum zinc transporter 8 antibody (ZnT-8A) in T1DM patients (n =80),their direct relatives (n =100) and normal subjects (n =100) were detected by radioimmunoprecipitation assay.The islet cell antibody (ICA),glutamic acid decarboxylase antibody (GADA),protein tyrosine phosphatase autoantibody (IA-2A) and insulin autoantibody (IAA) were detected by Western Blot.The combined detection efficacy of different antibodies was evaluated with ROC curve and the 3-year onset of direct relatives was analyzed.Results The antibodies detection rates of serum ZnT-8A,IA-2A,IAA,GADA and ICA were significantly higher in T1DM group than direct relatives group and healthy group (P ＜ 0.05),and the detection rates of above antibodies were significantly higher in direct relatives group than the healthy group (P ＜ 0.05).The highest total positive rate detected by the five antibodies was 91.25％,and the highest total positive rates detected by the combination of 2,3 and 4 antibodies were 83.75％,87.5％ and 90.0％,respectively.The area under ROC (AUC) of the 5 antibodies was the largest but there was no significant difference in AUC among different combinations of antibodies.All positive rates detected by combined antibodies were significantly higher than that of detection of ZnT-8A antibody alone (P ＜ 0.05).During 3-year follow-up,direct relatives with ZnT-8A and GADA were diagnosed with T1DM,and there were no symptoms in the other individuals.Conclusion The combined detection of 5 antibodies can improve the diagnosis rate of T1DM.The combined detection of Zn T-8A and GADA is of great value in timely and accurate classification of diabetes mellitus,and they also can be used as indicators for epidemiological screening of direct relatives of T1DM patients.