GAD65抗原表位在1型糖尿病和成人隐匿性自身免疫糖尿病中的临床应用

GAD65 antibody epitope patterns of Type 1 diabetes and LADA patients

目的探讨1型糖尿病(T1DM)及成人隐匿性自身免疫糖尿病(LADA)GAD65抗原表位反应的差异及临床应用。方法采用放射配体法对112例T1DM患者,107例LADA患者及100例正常对照进行谷氨酸脱羧酶抗体(GADA)对GAD67、GAD65氨基端(GAD65-N)、GAD65中段(GAD65-M)、GAD65羧基端(GAD65-C)抗原表位反应性研究,放射免疫法检测甲状腺自身抗体。结果①T1DM和LADA患者GADA与GAD67、GAD65-N端、GAD65-M段及GAD65-C端的结合率分别为4.5%、11.6%、30.4%、68.8%和11.2%、22.4%、31.8%、47.7%,均显著高于正常对照(P<0.05)。②T1DM患者GADA与GAD65-C端结合率高于LADA患者(68.8%vs 47.7%,P=0.002)。LADA患者GADA与GAD65-N端结合率高于T1DM患者(22.4%vs11.6%,P<0.05)。③同时识别GAD65-M段及-C端的LADA患者高滴度GADA(GADA≥0.3)所占比例高、甲状腺自身抗体阳性率高、更多依赖胰岛素治疗、空腹及餐后C肽水平较低(均P<0.05)。结论 T1DM和LA-DA患者对GAD65抗原表位识别存在差异,提示两者有不同免疫反应过程。而同时识别GAD65-M及-C端抗原表位的LADA临床表现更倾向于T1DM。

【Objective】To compare the epitopes of GAD65 autoantibodies in type 1 diabetes（T1DM） and latent autoimmune diabetes in adults（LADA） patients.【Methods】The glutamic acid decarboxylase antibody（GADA） levels and their relative epitope reactivities to N-terminal（GAD65-N）,middle（GAD65-M） and C-terminal（GAD65-C） regions of human GAD65 were determined by radioligand immunoassay in 112 T1DM,107 LADA patients and 100 controls.Thyroid peroxidase antibody（TPO-Ab） and thyroglobulin antibody（TG-Ab） were measured by radioimmunoassay.【Result】① Antibodies reactivity to N-terminal,middle,C-terminal epitope of GAD65 was 11.6%,30.4%,68.8% in T1DM patients and 22.4%,31.8%,47.7% in LADA patients,respectively.②The N-terminal of GAD65 was recognized by 22.4% of LADA patients compared with 11.6% in T1DM patients（P 0.05）.More T1DM patients recognized C-terminal of GAD65 than LADA patients（68.8% vs 47.7%,P =0.002）.③LADA patients with M＋C-predominant GAD65Ab reactivity had higher risk for thyroid autoimmunity,lower C-peptide level,higher titer of GADA（GADA≥0.3）,and a need for insulin therapy compared with LADA patients（P 0.05）.【Conclusion】The difference in the binding pattern of GAD65Ab of LADA patients compared with that of T1DM supports the notion that the disease process may differ between these two type of patients.LADA patients with M ＋C-predominant GAD65 reactivity have clinical features more similar to those of T1DM patient.