著者

Eiji Kawasaki

出版者

The Japanese Society for Pediatric Endocrinology

雑誌

Clinical Pediatric Endocrinology (ISSN:09185739)

巻号頁・発行日

vol.23, no.4, pp.99-105, 2014 (Released:2014-11-06)

参考文献数

19

被引用文献数

26 95

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Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic β cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset.

著者

Eiji Kawasaki

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.7, pp.531-537, 2012 (Released:2012-07-31)

参考文献数

31

被引用文献数

13 44

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Zinc is essential for the proper storage, secretion, and the action of insulin and is transported from cytoplasm to insulin secretory granules in the pancreatic β-cells by SLC30A zinc transporters (ZnT). ZnT8 is specifically expressed in the pancreatic β-cells and has been identified as a novel target autoantigen in patients with type 1 diabetes. Autoantibodies to ZnT8 (ZnT8A) are detected in 50-60% of Japanese patients with acute-onset and 20% with slow-onset type 1 diabetes. Furthermore, humoral autoreactivity to ZnT8 is unique in terms of a key determinant, which is not reported on other islet autoantigens such as insulin, glutamic acid decarboxylase, or the protein tyrosine phosphatase-related molecules IA-2. Type 2 diabetes-associated nonsynonymous single nucleotide polymorphism in SLC30A8 (the gene of ZnT8), rs13266634 (Arg325Trp), modulates ZnT8A specificities thereby indicating that this amino acid substitution has the critical role in antibody binding. The humoral autoreactivity to ZnT8 depends on the clinical phenotype, which may provide clues to understand the role of this protein in the pathogenesis of type 1 diabetes.