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目的探讨伴与不伴甲状腺自身免疫的1型糖尿病(T1DM)及成人隐匿性自身免疫性糖尿病(LADA)患者GAD65抗原表位反应性的差异。方法对112例T1DM、107例LADA患者采用放射配体法检测分析谷氨酸脱羧酶抗体(GADA)对GAD67、GAD65氨基端(GAD65-N)、GAD65中段(GAD65 M)、GAD65羧基端(GAD65-C)抗原表位反应性,并采用放射免疫法检测甲状腺过氧化物酶抗体(TPO-Ab)、甲状腺球蛋白抗体(TG-Ab)。结果 (1)甲状腺自身抗体阳性的T1DM患者GADA对GAD65-M段、GAD65-C端抗原的识别率均高于甲状腺自身抗体阴性组(48.0% vs16.1%和82.0% vs58.1%,P均<0.05)。(2)与甲状腺自身抗体阴性者相比,甲状腺自身抗体阳性的LADA患者GADA与GAD65-M段、GAD65-C端结合率较高(51.6% vs 23.7%和70.9% vs 38.2%,P 均<0.05)。(3)Logistic回归分析显示,GADA同时识别GAD65-M段及-C端抗原表位是T1DM及LADA患者发生甲状腺自身免疫的危险因素(OR=5.016和4.724,P 均<0.05)。结论 GADA同时识别GAD65-M段及-C端抗原表位的自身免疫糖尿病患者易于发生甲状腺自身免疫紊乱;GAD65抗原表位反应性检测有助于预测T1DM及LADA患者发生甲状腺自身免疫的风险。
Objective To investigate the difference of GAD65 epitope reactivity between type 1 diabetes mellitus (T1DM) and latent occlusive autoimmune diabetes (LADA) in patients with and without thyroid autoimmunity. Methods GAD67, the GAD65-N, GAD65 M, GAD65 carboxyterminal (GAD65) and GAD65 (GAD65 M) were detected by radioligand assay in 112 patients with T1DM and 107 patients with LADA. -C) antigenic epitopes were detected. Thyroperoxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab) were detected by radioimmunoassay. Results (1) The positive rate of GAD65-M and GAD65-C antigen in thyroid autoantibody positive T1DM patients was higher than that in thyroid autoantibody negative patients (48.0% vs16.1% and82.0% vs58.1%, P All <0.05). (2) Compared with GAD65-M and GAD65-C, the GADA positive rate in thyroid autoantibodies was higher in thyroid autoantibodies than in thyroid autoantibodies (51.6% vs 23.7% and 70.9% vs 38.2%, P < 0.05). (3) Logistic regression analysis showed that GADA identified both GAD65-M and C-terminal epitopes as risk factors for thyroid autoimmunity in both T1DM and LADA patients (OR = 5.016 and 4.724, P <0.05). Conclusions GADA can detect thyroid autoimmune disorder easily in patients with autoimmune diabetes with both GAD65-M and C-terminal epitopes. GAD65 epitope reactivity test can be used to predict the risk of thyroid autoimmunity in patients with T1DM and LADA.