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

• Published in: The FASEB journal 2017-09, Vol.31 (9), p.4053-4063
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Autoantibodies; autoantibody; Autoimmune diseases; Beta cells; Biomarkers; C-Peptide - metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - metabolism; Epitopes; Female; GAD65; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Glutamate decarboxylase; Glutamic acid; Humans; Male; Mathematical models; Mice; Mice, Inbred NOD; nonobese diabetic; Patients; Predictions; Proteins; Rodents; Schwann cells; T cell receptors; type 1 diabetes; type 2 diabetes; Zinc; Zinc transporter
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201700110R

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‐Ay 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. FASEB J. 31, 4053–4063 (2017). www.fasebj.org—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 Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes. FASEB J. 31, 4053–4063 (2017)