期刊
DIABETIC MEDICINE
卷 39, 期 9, 页码 -出版社
WILEY
DOI: 10.1111/dme.14860
关键词
antibody; cytokines; interferon-gamma; proinsulin; T cells; type 1 diabetes
资金
- Novo Nordisk
- Juvenile Diabetes Research Foundation International
- European Research Foundation for the Study of Diabetes (EFSD)
- European Programme in Type 1 Diabetes
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- National Institute of Child Health and Human Development [UC4 DK106993]
This study aimed to evaluate T cell phenotypes and metabolic profiles in high-risk individuals who progressed to type 1 diabetes. The results showed a prevalent proinflammatory T cell response in these individuals, which could potentially be used for disease staging and identifying autoantibody-positive individuals.
Aims: In the current study we aimed to evaluat T cell phenotypes and metabolic profiles in high-risk individuals who progressed to type 1 diabetes compared to those remaining disease free. Methods: A Fluorspot assay was used to examine T cell responses to a panel of islet autoantigen peptides in samples obtained 6- and 30-months preceding disease onset and at the same timepoints in non-progressors. Results: We noted a significant increase in the magnitude of the proinflammatory interferon-gamma response to proinsulin and insulin peptides in individuals who progressed to type 1 diabetes. In contrast, in the non-progressors, we observed an increase in the regulatory IL-10 response to proinsulin peptides. Furthermore, the T cell responses to the islet peptide panel predisposed towards a proinflammatory interferon-gamma bias in the progressors. Conclusions: Collectively, these data suggest that a proinflammatory T cell response is prevalent in high-risk individuals who progress to type 1 diabetes and can be detected up to 6 months prior to onset of disease. This observation, albeit in a small cohort, can potentially be harnessed in disease staging, particularly in identifying autoantibody-positive individuals transitioning from stage 2 (dysglycemia present and pre-symptomatic) to stage 3 (dysglycemia present and symptomatic). The detection of these different T cell phenotypes in progressors and non-progressors suggests the presence of disease endotypes.
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