4.3 Article

Antigen Targets of Type 1 Diabetes Autoimmunity

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Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/cshperspect.a007781

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Funding

  1. UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
  2. Juvenile Diabetes Research Foundation [JDRF: 7-2005-877, 1-2007-1803]
  3. Dutch Diabetes Research Foundation
  4. ZonMW
  5. JDRF
  6. EU FP7 EU Framework 7 Large-Scale Focused Collaborative Research Project on Natural Immunomodulators as Novel Immunotherapies for Type 1 Diabetes (NAIMIT)

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Type 1 diabetes is characterized by recognition of one or more beta-cell proteins by the immune system. The list of target antigens in this disease is ever increasing and it is conceivable that additional islet autoantigens, possibly including pivotal beta-cell targets, remain to be discovered. Many knowledge gaps remain with respect to the disorder's pathogenesis, including the cause of loss of tolerance to islet autoantigens and an explanation as to why targeting of proteins with a distribution of expression beyond beta cells may result in selective beta-cell destruction and type 1 diabetes. Yet, our knowledge of beta-cell autoantigens has already led to translation into tissue-specific immune intervention strategies that are currently being assessed in clinical trials for their efficacy to halt or delay disease progression to type 1 diabetes, as well as to reverse type 1 diabetes. Here we will discuss recently gained insights into the identity, biology, structure, and presentation of islet antigens in relation to disease heterogeneity and beta-cell destruction.

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