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胶质纤维酸性蛋白(GFAP)是预测自身免疫性糖尿病的一种新型生物标志物。

Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes.

作者信息

Pang Zhengda, Kushiyama Akifumi, Sun Jiao, Kikuchi Takako, Yamazaki Hiroki, Iwamoto Yasuhiko, Koriyama Hiroshi, Yoshida Shota, Shimamura Munehisa, Higuchi Masayoshi, Kawano Tomohiro, Takami Yoichi, Rakugi Hiromi, Morishita Ryuichi, Nakagami Hironori

机构信息

Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

FASEB J. 2017 Sep;31(9):4053-4063. doi: 10.1096/fj.201700110R. Epub 2017 May 25.

Abstract

Glial fibrillary acidic protein (GFAP) is expressed in peri-islet Schwann cells, as well as in glia cells, and has been reported to be an autoantigen candidate for type 1 diabetes mellitus (T1DM). We confirmed that the production of the autoantibodies GFAP and glutamic acid decarboxylase 65 (GAD65) was increased and inversely correlated with the concentration of secreted C peptide in female nonobese diabetic mice (T1DM model). Importantly, the development of T1DM in female nonobese diabetic mice at 30 wk of age was predicted by the positive GFAP autoantibody titer at 17 wk. The production of GFAP and GAD65 autoantibodies was also increased in KK-A mice [type 2 diabetes mellitus (T2DM) model]. In patients with diabetes mellitus, GFAP autoantibody levels were increased in patients with either T1DM or T2DM, and were significantly associated with GAD65 autoantibodies but not zinc transporter 8 autoantibodies. Furthermore, we identified a B-cell epitope of GFAP corresponding to the GFAP autoantibody in both mice and patients with diabetes. Thus, these results indicate that autoantibodies against GFAP could serve as a predictive marker for the development of overt autoimmune diabetes.-Pang, Z., Kushiyama, A., Sun, J., Kikuchi, T., Yamazaki, H., Iwamoto, Y., Koriyama, H., Yoshida, S., Shimamura, M., Higuchi, M., Kawano, T., Takami, Y., Rakugi, H., Morishita, R., Nakagumi, H. Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes.

摘要

胶质纤维酸性蛋白(GFAP)在胰岛周围的雪旺细胞以及神经胶质细胞中表达,并且据报道它是1型糖尿病(T1DM)的自身抗原候选物。我们证实,在雌性非肥胖糖尿病小鼠(T1DM模型)中,自身抗体GFAP和谷氨酸脱羧酶65(GAD65)的产生增加,且与分泌的C肽浓度呈负相关。重要的是,17周时GFAP自身抗体滴度为阳性可预测30周龄雌性非肥胖糖尿病小鼠T1DM的发生。在KK-A小鼠[2型糖尿病(T2DM)模型]中,GFAP和GAD65自身抗体的产生也增加。在糖尿病患者中,T1DM或T2DM患者的GFAP自身抗体水平均升高,并且与GAD65自身抗体显著相关,但与锌转运体8自身抗体无关。此外,我们在糖尿病小鼠和患者中均鉴定出了与GFAP自身抗体相对应的GFAP的B细胞表位。因此,这些结果表明,针对GFAP的自身抗体可作为显性自身免疫性糖尿病发生的预测标志物。-庞,Z.,串山,A.,孙,J.,菊池,T.,山崎,H.,岩本,Y.,有山,H.,吉田,S.,岛村,M.,樋口,M.,川野,T.,高见,Y.,rakugi,H.,森下,R.,中久美,H. 胶质纤维酸性蛋白(GFAP)是预测自身免疫性糖尿病的新型生物标志物。

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