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Prediction and Pathogenesis in Type 1 Diabetes
Open accessAbstract
A combination of genetic and immunological features is useful for prediction of autoimmune diabetes. Patterns of immune response correspond to the progression from a preclinical phase of disease to end-stage islet damage, with biomarkers indicating transition from susceptibility to active autoimmunity, and to a final loss of immune regulation. Here, we review the markers that provide evidence for immunological checkpoint failure and that also provide tools for assessment of individualized disease risk. When viewed in the context of genetic variation that influences immune response thresholds, progression from susceptibility to overt disease displays predictable modalities of clinical presentation resulting from a sequential series of failed homeostatic checkpoints for selection and activation of immunity.
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“More than 90% of individuals with newly diagnosed type 1 diabetes have one or more of the following autoantibodies at disease onset:53 those reactive to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma-associated autoantigen 2 (IA2A), and zinc transporter 8 (ZnT8A).65”
From Type 1 diabetes (2014) · cites this paper as [65]
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Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60591-7 · Cited by 2,931
Diabetes mellitus: The epidemic of the century
Kharroubi, A. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i6.850 · Cited by 1,352
Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective
Zaccardi, F., Webb, D. R., Yates, T. E., & Davies, M. J. (2015) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133281 · Cited by 614
Gut microbiota, obesity and diabetes
Patterson, E., Ryan, P. M., Cryan, J. F., Dinan, T. G., Ross, R. P., Fitzgerald, G. F., & Stanton, C. (2016) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133285 · Cited by 552
Is autoimmunity the Achilles' heel of cancer immunotherapy?
June, C. H., Warshauer, J. T., & Bluestone, J. A. (2017) · Nature Medicine · doi:10.1038/nm.4321 · Cited by 445
Metadata
- Authors
- Ziegler, A.-G., & Nepom, G. T.
- Affiliations
- TUM Klinikum (DE)
- Benaroya Research Institute (US)
- Corresponding author
- Ziegler, Anette-G.
- Nepom, Gerald T.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 32
- Issue
- 4
- Pages
- 468-478
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2861716
- OpenAlex
- W2047768051
- Cited by
- 346
- References
- 101
- Citations by year
- 2026: 5 · 2025: 21 · 2024: 20 · 2023: 12 · 2022: 15 · 2021: 25 · 2020: 18 · 2019: 19 · 2018: 26 · 2017: 10 · 2016: 26 · 2015: 30 · 2014: 28 · 2013: 29 · 2012: 25
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- National Institutes of Health
- Juvenile Diabetes Research Foundation International
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 1 diabetes, autoimmune diabetes, disease prediction, pathogenesis, genetic susceptibility, immune response, biomarkers, immune checkpoint, immune regulation, islet autoimmunity, disease risk assessment, preclinical stage, immune homeostasis
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Humans, Risk Factors, Genetic Variation, Biomarkers, Genetic Predisposition to Disease
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