Subtyping of Type 1 Diabetes as Classified by Anti-GAD Antibody, IgE Levels, and Tyrosine kinase 2 (TYK2) Promoter Variant in the Japanese
| Autor: | Nobutaka Tsutsu, Shiori Kondo, Keiichiro Mine, Kanako Hirakawa, Yasunobu Yoshikai, Keizo Anzai, Fumiko Kojima, Seiho Nagafuchi, Masae Minami, Akira Okada, Yumi Hibio, Hironori Kurisaki, Shuji Fujimoto, Yasushi Yokogawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system diseases lcsh:Medicine Type 1 diabetes (T1D) medicine.disease_cause Immunoglobulin E Autoimmunity Pathogenesis 0302 clinical medicine Th1/Th2 lcsh:R5-920 Th2 type 2 T helper TYK2 Tyrosine kinase 2 T1D Type 1 diabetes YH young healthy controls General Medicine Protein-Tyrosine Kinases Subtyping Tyrosine kinase 2 (TYK2) Virus Tyrosine kinase 2 Anti-GAD Ab anti-glutamic acid decarboxylase antibody IgE lcsh:Medicine (General) Research Paper endocrine system 030209 endocrinology & metabolism Biology Antiviral Agents General Biochemistry Genetics and Molecular Biology Th1 type 1 T helper 03 medical and health sciences Diabetes mellitus medicine Diabetes Mellitus Humans TYK2 Kinase Type 1 diabetes lcsh:R nutritional and metabolic diseases HIES hyper-IgE syndrome medicine.disease OR odds ratio CI confidence interval 030104 developmental biology Anti-GAD Immunology biology.protein Interferons |
| Zdroj: | EBioMedicine EBioMedicine, Vol 23, Iss C, Pp 46-51 (2017) |
| ISSN: | 2352-3964 |
| Popis: | Objective Type 1 diabetes (T1D) is known to be caused by Th1 cell-dependent autoimmunity. Recently, we reported that TYK2 promoter variant serves as a putative virus-induced diabetes susceptibility gene associated with deteriorated interferon-dependent antiviral response. TYK2 is also related to HIES, that is, Th2 cell-dependent. Therefore, TYK2 promoter variant may be also associated with the pathogenesis of T1D, modulating Th1/Th2 balance. Research Design and Methods We assessed the association between anti- GAD Ab, IgE levels, and TYK2 promoter variant among 313 T1D patients, 184 T2D patients, and 264 YH controls in the Japanese. Results T1D patients had elevated IgE (median, 56.7 U/ml; p Highlights • T1D can be subtyped into 4 groups based on anti-GAD Ab, IgE levels and TYK2 promoter variant. • Only one subtype, without anti-GAD Ab or elevated IgE, was associated with TYK2 promoter variant and flu-like syndrome. • Profiling of T1D by anti-GAD Ab and IgE levels is useful to realize the variable immuno-pathogenesis of T1D. Since TYK2 gene is associated with T1D and HIES, we assessed the association between anti-GAD Ab, IgE levels, and TYK2 promoter variant in patients with T1D. Consequently, T1D can be subtyped into 4 distinct groups based on these clinical laboratory and genetic markers. Only those patients without anti-GAD Ab or elevated IgE were associated with TYK2 promoter variant and with flu-like syndrome at the diabetes onset, suggestive of association with virus-induced diabetes. This study describes the usefulness of subtyping of T1D with variable immunological bases and provides a clue to delineate the pathogenesis of T1D. |
| Databáze: | OpenAIRE |
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