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Etiology of fulminant type 1 diabetes with reference to enteroviral infection

暴发性 1 型糖尿病的病因学与肠道病毒感染相关

基本信息

批准号：
16590896
负责人：
HANAFUSA Toshiaki
金额：
$ 2.3万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590896/
关键词：
diabetes enterovirus VP1 immunohistochemistry fulminant diabetes IDDM enterovirus coxsackie virus biopsy immunohistochemistry type 1 diabetes viral infection

项目摘要

1.Enterovirus antibodies in the sera of patients with fulminant type 1 diabetes.We have investigated 19 patients with recent-onset fulminant type 1 diabetes, 18 patients with recent-onset typical type 1A diabetes, and 19 healthy controls. IgM, IgG, and IgA subclasses of antibodies to enterovirus were determined by ELISA. IgA antibody titres to enterovirus were significantly higher in fulminant type 1 diabetes than in typical type 1A diabetes (p=0.033) and controls (p=0.0003). IgM antibodies to enterovirus were not detected in any subject. In conclusion, high titres of enterovirus IgA-antibodies in serum suggest recurrent enterovirus infections in fulminant type 1 diabetic patients indicating higher susceptibility to enteroviral infections among them. Such infections may have pathogenetic importance for the triggering of fulminant type 1 diabetes.2.Identification of enterovirus-derived antigen in autopsy specimens with fulminant type 1 diabetesWe analyzed an autopsy case of fulminant type 1 diabetes died soon after the onset of overt diabetes by using immunohistochemical methods. We found positive staining of enterovirus capsid antigen, VP1, in the specimens. It was strongly stained in exocrine pancreas and weakly in islet area with remained beta cells. These findings suggest that enterovirus targeted to human pancreas at least in part of fulminant diabetes.

1.暴发型1型糖尿病患者血清中肠道病毒抗体的检测我们研究了19例新近发病的暴发型1型糖尿病患者、18例新近发病的典型1A型糖尿病患者和19名健康对照者。用ELISA法测定肠道病毒抗体的IgM、IgG和伊加亚类。肠道病毒伊加抗体滴度在暴发性1型糖尿病中显著高于典型1A型糖尿病（p=0.033）和对照组（p=0.0003）。在任何受试者中均未检测到肠道病毒IgM抗体。总之，血清中肠道病毒IgA抗体的高滴度提示暴发性1型糖尿病患者中肠道病毒感染复发，表明他们对肠道病毒感染的易感性较高。2.暴发性1型糖尿病尸检标本中肠道病毒抗原的检测应用免疫组化方法对1例暴发性1型糖尿病尸检标本进行了分析。我们发现肠道病毒衣壳抗原VP1阳性染色的标本。胰腺外分泌部强阳性，胰岛区弱阳性，胰岛内有β细胞残留。这些发现表明肠道病毒至少在部分暴发性糖尿病中靶向人类胰腺。