Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD(65) and IA2 marks the early phases of autoimmune response in type 1 diabetes
Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD(65) and IA2 marks the early phases of autoimmune response in type 1 diabetes
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DOI：
10.1172/jci118732
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发表时间：
1996-06-15
影响因子：
15.9
通讯作者：
Baekkeskov, S
中科院分区：
文献类型：
--
作者：
Aanstoot, HJ;Kang, SM;Baekkeskov, S
免疫沉淀抗谷氨酸脱羧酶自身抗体GAD(65)和/或酪氨酸磷酸酶IA2存在于大多数经历胰岛β细胞破坏和发展的1型糖尿病患者中。在这里，我们鉴定了第三种胰岛细胞自身抗原，一种新的38-kD蛋白，它是与糖尿病前期患者和新诊断的1型糖尿病患者的血清特异性免疫沉淀的。Glima 38是一种两亲膜糖蛋白，在胰岛和神经细胞系中特异表达，具有GAD(65)和IA2的神经内分泌表达模式。去除N-连接的碳水化合物导致22,000 M(R)Glima 38蛋白在16/86(19%)的新诊断患者中检测到自身抗体，其中包括3名发病迅速的幼儿，在6/44(14%)糖尿病前期患者中检测到临床发作前的几个梨的自身抗体。两组GAD(65例)和Glima 38抗体的累积发生率分别为83%和80%，GAD(65例)、Glima 38和IA2抗体的累积发生率分别为91%和84%。GAD(65)、IA2和Glima 38代表了免疫沉淀的三个不同的目标，即与β细胞破坏和1型糖尿病相关的免疫球蛋白自身抗体。
Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD(65), and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes, Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD(65) and IA2. Removal of N-Linked carbohydrates results in a protein of 22,000 M(r) Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several pears before clinical onset. The cumulative incidence of GAD(65) and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD(65), glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. GAD(65), IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes.