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Subtyping of Type 1 Diabetes as Classified by Anti-GAD Antibody, IgE Levels, and Tyrosine kinase 2 (TYK2) Promoter Variant in the Japanese.
- Source :
-
EBioMedicine [EBioMedicine] 2017 Sep; Vol. 23, pp. 46-51. Date of Electronic Publication: 2017 Aug 12. - Publication Year :
- 2017
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Abstract
- 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.<br />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.<br />Results: T1D patients had elevated IgE (median, 56.7U/ml; p<0.0001) compared with T2D patients (22.5U/ml) and controls (43.3U/ml). Contrary to our expectations, there was no correlation between TYK2 promoter variant and IgE levels. We found that T1D could be subtyped as four groups based on anti-GAD Ab and IgE profile: Subtype 1, anti-GAD Ab positive and non-elevated IgE (47.0%); Subtype 2, anti-GAD Ab negative and non-elevated IgE (35.1%); Subtype 3, anti-GAD Ab positive and elevated IgE (10.9%); and Subtype 4, anti-GAD Ab negative and elevated IgE (7.0%). In Subtype 2, a significantly higher incidence was observed in T1D cases carrying the TYK2 promoter variant (OR, 2.60; 95%CI, 1.03-6.97; p=0.032), and also showing a flu-like syndrome at diabetes onset (OR, 2.34; 95%CI, 1.27-4.35; p=0.003).<br />Interpretation: Anti-GAD Ab and IgE profiling helps classifying T1D into four groups that recognize variable pathogenic bases of T1D.<br /> (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Autoantigens immunology
Autoimmunity
Child
Diabetes Mellitus, Type 2
Disease Susceptibility
Female
Genotype
Humans
Japan
Male
Middle Aged
Odds Ratio
Young Adult
Autoantibodies immunology
Diabetes Mellitus, Type 1 genetics
Diabetes Mellitus, Type 1 immunology
Genetic Variation
Immunoglobulin E immunology
Promoter Regions, Genetic
TYK2 Kinase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 23
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 28826655
- Full Text :
- https://doi.org/10.1016/j.ebiom.2017.08.012