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Progression of type...
Progression of type 1 diabetes is associated with high levels of soluble PD-1 in islet autoantibody-positive children
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- Bruzzaniti, Sara (author)
- CNR, Italy
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- Piemonte, Erica (author)
- Univ Naples Federico II, Italy
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- Bruzzese, Dario (author)
- Univ Napoli Federico II, Italy
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- Lepore, Maria Teresa (author)
- CNR, Italy
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- Strollo, Rocky (author)
- Univ Telemat San Raffaele Roma, Italy
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- Izzo, Lavinia (author)
- Univ Naples Federico II, Italy
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- Di Candia, Francesca (author)
- Univ Napoli Federico II, Italy
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- Franzese, Adriana (author)
- Univ Napoli Federico II, Italy
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- Bifulco, Maurizio (author)
- Univ Naples Federico II, Italy
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- Mozzillo, Enza (author)
- Univ Napoli Federico II, Italy
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- Ludvigsson, Johnny (author)
- Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
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- Matarese, Giuseppe (author)
- CNR, Italy; Univ Naples Federico II, Italy
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- Galgani, Mario (author)
- CNR, Italy; Univ Naples Federico II, Italy
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428.
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Aims/hypothesisType 1 diabetes is an autoimmune disorder that is characterised by destruction of pancreatic beta cells by autoreactive T lymphocytes. Although islet autoantibodies (AAb) are an indicator of disease progression, specific immune biomarkers that can be used as target molecules to halt development of type 1 diabetes have not been discovered. Soluble immune checkpoint molecules (sICM) play a pivotal role in counteracting excessive lymphocyte responses, but their role in type 1 diabetes is unexplored. In this longitudinal study, we measured sICM levels in AAb-positive (AAb+) children to identify molecules related to type 1 diabetes progression.MethodsWe measured the levels of 14 sICM in the sera of AAb+ children (n=57) compared to those with recent-onset type 1 diabetes (n=79) and healthy children (n=44), obtained from two cohorts. AAb+ children were followed up and divided based on their progression to type 1 diabetes (AAbP) or not (AAbNP) (if they lost islet autoimmunity and did not develop disease in subsequent years). sICM were also measured in the sample taken at the visit closest to disease onset in AAbP children.ResultsWe found that AAb+ children had a distinct sICM profile compared with healthy children and those with recent-onset type 1 diabetes. In addition, AAb+ children who progressed to type 1 diabetes (AAbP) had higher sICM concentrations than non-progressors (AAbNP). Further, sICM levels decreased in AAbP children close to disease onset. Application of Cox regression models highlighted that high concentrations of soluble programmed cell death protein 1 (sPD-1) are associated with type 1 diabetes progression (HR 1.71; 95% CI 1.16, 2.51; p=0.007).Conclusions/interpretationThis study reveals an sICM profile that is dysregulated during the preclinical stage of type 1 diabetes, and identifies sPD-1 as a pathophysiologically-relevant molecule that is associated with disease progression, offering a potential target for early interventions in autoimmune diabetes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Islet autoantibodies; Prediction of type 1 diabetes; Soluble immune checkpoint molecules; Soluble PD-1; Type 1 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bruzzaniti, Sara
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Piemonte, Erica
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Bruzzese, Dario
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Lepore, Maria Te ...
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Strollo, Rocky
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Izzo, Lavinia
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show more...
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Di Candia, Franc ...
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Franzese, Adrian ...
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Bifulco, Maurizi ...
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Mozzillo, Enza
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Ludvigsson, John ...
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Matarese, Giusep ...
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Galgani, Mario
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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Linköping University