Etiopathogenesis of Insulin Autoimmunity

Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction...

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Autores principales: Kanatsuna, Norio, Papadopoulos, George K., Moustakas, Antonis K., Lenmark, Åke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335545/
https://www.ncbi.nlm.nih.gov/pubmed/22567309
http://dx.doi.org/10.1155/2012/457546
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author Kanatsuna, Norio
Papadopoulos, George K.
Moustakas, Antonis K.
Lenmark, Åke
author_facet Kanatsuna, Norio
Papadopoulos, George K.
Moustakas, Antonis K.
Lenmark, Åke
author_sort Kanatsuna, Norio
collection PubMed
description Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.
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spelling pubmed-33355452012-05-07 Etiopathogenesis of Insulin Autoimmunity Kanatsuna, Norio Papadopoulos, George K. Moustakas, Antonis K. Lenmark, Åke Anat Res Int Review Article Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity. Hindawi Publishing Corporation 2012 2012-02-22 /pmc/articles/PMC3335545/ /pubmed/22567309 http://dx.doi.org/10.1155/2012/457546 Text en Copyright © 2012 Norio Kanatsuna et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Kanatsuna, Norio
Papadopoulos, George K.
Moustakas, Antonis K.
Lenmark, Åke
Etiopathogenesis of Insulin Autoimmunity
title Etiopathogenesis of Insulin Autoimmunity
title_full Etiopathogenesis of Insulin Autoimmunity
title_fullStr Etiopathogenesis of Insulin Autoimmunity
title_full_unstemmed Etiopathogenesis of Insulin Autoimmunity
title_short Etiopathogenesis of Insulin Autoimmunity
title_sort etiopathogenesis of insulin autoimmunity
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335545/
https://www.ncbi.nlm.nih.gov/pubmed/22567309
http://dx.doi.org/10.1155/2012/457546
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