Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens

Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens
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DOI:
10.1016/j.clim.2008.01.018
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发表时间:
2008-06-01
影响因子:
8.6
通讯作者:
Notkins, Abner L.
Notkins, Abner L.
中科院分区:
医学3区
文献类型:
--
作者:
Hirai, Hiroki;Miura, Junnosuke;Notkins, Abner L.

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1型糖尿病的四种主要自身抗原(IA-2、IA-2 β、GAD 65和胰岛素)都与致密核心或突触囊泡相关。这提出了其他分泌囊泡相关蛋白可能是1型糖尿病自身免疫反应的靶点的可能性。为了验证这一假设,56蛋白,其中三分之二是与分泌囊泡,在体外转录/翻译制备和筛选自身抗体的液相放射免疫沉淀。两个分泌囊泡相关蛋白,VAMP 2和NPY,被确定为新的次要自身抗原,分别为21%和9%,200例1型糖尿病血清反应阳性。这些发现支持了一个假设,即分泌囊泡相关蛋白是特别重要的,但不是唯一的,在1型糖尿病的自身免疫反应的目标。人类蛋白质组的选择性筛选为识别自身免疫性疾病中的新自身抗原提供了有用的方法。(c)2008年爱思唯尔公司All rights reserved.
The four major autoantigens (IA-2, IA-2 beta, GAD65 and insulin) of type 1 diabetes are all associated with dense core or synaptic vesicles. This raised the possibility that other secretory vesicle-associated proteins might be targets of the autoimmune response in type 1 diabetes. To test this hypothesis 56 proteins, two-thirds of which are associated with secretory vesicles, were prepared by in vitro transcription/translation and screened for autoantibodies by liquid phase radioimmunoprecipitation. Two secretory vesicle-associated proteins, VAMP2 and NPY, were identified as new minor autoantigens with 21% and 9%, respectively, of 200 type 1 diabetes sera reacting positively. These findings add support to the hypothesis that secretory vesicle-associated proteins are particularly important, but not the exclusive, targets of the autoimmune response in type 1 diabetes. Selective screening of the human proteome offers a useful approach for identifying new autoantigens in autoimmune diseases. (c) 2008 Elsevier Inc. All rights reserved.