Evaluating T cell responses prior to the onset of type 1 diabetes

TY - JOUR

T1 - Evaluating T cell responses prior to the onset of type 1 diabetes

AU - Arif, Sefina

AU - Yusuf, Norkhairin

AU - Domingo-Vila, Clara

AU - Liu, Yuk Fun

AU - Bingley, Polly J.

AU - Peakman, Mark

N1 - Funding Information: We acknowledge the support of the Type 1 Diabetes TrialNet Study Group’s Pathway to Prevention Study for this TrialNet Ancillary Study. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreement UC4 DK106993, and the JDRF. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF. We would like to acknowledge the UK TrialNet Team at the University of Bristol for collecting samples and thank the participants and their families for providing samples. Funding Information: This work was supported by a research grant from the European Programme in Type 1 Diabetes and funded by European Research Foundation for the Study of Diabetes (EFSD), Juvenile Diabetes Research Foundation (JDRF) and Novo Nordisk. Funding Information: We acknowledge the support of the Type 1 Diabetes TrialNet Study Group’s Pathway to Prevention Study for this TrialNet Ancillary Study. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreement UC4 DK106993, and the JDRF. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF. We would like to acknowledge the UK TrialNet Team at the University of Bristol for collecting samples and thank the participants and their families for providing samples. Publisher Copyright: © 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

PY - 2022/9

Y1 - 2022/9

N2 - 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-γ 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-γ 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.

AB - 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-γ 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-γ 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.

KW - antibody

KW - cytokines

KW - interferon-γ

KW - proinsulin

KW - T cells

KW - type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85129603925&partnerID=8YFLogxK

U2 - 10.1111/dme.14860

DO - 10.1111/dme.14860

M3 - Article

C2 - 35477909

AN - SCOPUS:85129603925

SN - 0742-3071

VL - 39

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 9

M1 - e14860

ER -