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Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children

AIMS/HYPOTHESIS: We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are m...

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Autores principales: Strollo, Rocky, Vinci, Chiara, Napoli, Nicola, Pozzilli, Paolo, Ludvigsson, Johnny, Nissim, Ahuva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491589/
https://www.ncbi.nlm.nih.gov/pubmed/28526919
http://dx.doi.org/10.1007/s00125-017-4296-1
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author Strollo, Rocky
Vinci, Chiara
Napoli, Nicola
Pozzilli, Paolo
Ludvigsson, Johnny
Nissim, Ahuva
author_facet Strollo, Rocky
Vinci, Chiara
Napoli, Nicola
Pozzilli, Paolo
Ludvigsson, Johnny
Nissim, Ahuva
author_sort Strollo, Rocky
collection PubMed
description AIMS/HYPOTHESIS: We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes. METHODS: We used serum samples collected longitudinally from the ‘All Babies in Southeast Sweden (ABIS)’ cohort tested for the gold standard islet autoantibodies to insulin (IAA), GAD (GADA), tyrosine phosphatase 2 (IA-2A) and zinc transporter 8 (ZnT8A). We studied 23 children who progressed to type 1 diabetes (progr-T1D) and 63 children who did not progress to type 1 diabetes (NP) after a median follow-up of 10.8 years (interquartile range 7.7–12.8). Of the latter group, 32 were positive for one or more islet autoantibodies (NP-AAB(+)). oxPTM-INS-Ab to insulin modified by (•)OH or HOCl were measured by our developed ELISA platform. RESULTS: Antibodies to at least one oxPTM-INS were present in 91.3% of progr-T1D children. oxPTM-INS-Ab co-existed with GADA, IA-2A, IAA or ZnT8A in 65.2%, 56.5%, 38.9% and 33.3% progr-T1D children, respectively. In addition, oxPTM-INS-Ab were present in 17.4%, 26.1%, 38.9% and 41.6% of progr-T1D children who were negative for GADA, IA-2A, IAA and ZnT8A, respectively. (•)OH-INS-Ab were more common in progr-T1D children than in NP-AAB(+) children (82.6% vs 19%; p < 0.001) and allowed discrimination between progr-T1D and NP-AAB(+) children with 74% sensitivity and 91% specificity. None of the NP-AAB(−) children were positive for oxPTM-INS-Ab. CONCLUSIONS/INTERPRETATION: oxPTM-INS-Ab are present before the clinical onset of type 1 diabetes and can identify children progressing to type 1 diabetes.
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spelling pubmed-54915892017-07-13 Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children Strollo, Rocky Vinci, Chiara Napoli, Nicola Pozzilli, Paolo Ludvigsson, Johnny Nissim, Ahuva Diabetologia Article AIMS/HYPOTHESIS: We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes. METHODS: We used serum samples collected longitudinally from the ‘All Babies in Southeast Sweden (ABIS)’ cohort tested for the gold standard islet autoantibodies to insulin (IAA), GAD (GADA), tyrosine phosphatase 2 (IA-2A) and zinc transporter 8 (ZnT8A). We studied 23 children who progressed to type 1 diabetes (progr-T1D) and 63 children who did not progress to type 1 diabetes (NP) after a median follow-up of 10.8 years (interquartile range 7.7–12.8). Of the latter group, 32 were positive for one or more islet autoantibodies (NP-AAB(+)). oxPTM-INS-Ab to insulin modified by (•)OH or HOCl were measured by our developed ELISA platform. RESULTS: Antibodies to at least one oxPTM-INS were present in 91.3% of progr-T1D children. oxPTM-INS-Ab co-existed with GADA, IA-2A, IAA or ZnT8A in 65.2%, 56.5%, 38.9% and 33.3% progr-T1D children, respectively. In addition, oxPTM-INS-Ab were present in 17.4%, 26.1%, 38.9% and 41.6% of progr-T1D children who were negative for GADA, IA-2A, IAA and ZnT8A, respectively. (•)OH-INS-Ab were more common in progr-T1D children than in NP-AAB(+) children (82.6% vs 19%; p < 0.001) and allowed discrimination between progr-T1D and NP-AAB(+) children with 74% sensitivity and 91% specificity. None of the NP-AAB(−) children were positive for oxPTM-INS-Ab. CONCLUSIONS/INTERPRETATION: oxPTM-INS-Ab are present before the clinical onset of type 1 diabetes and can identify children progressing to type 1 diabetes. Springer Berlin Heidelberg 2017-05-20 2017 /pmc/articles/PMC5491589/ /pubmed/28526919 http://dx.doi.org/10.1007/s00125-017-4296-1 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Strollo, Rocky
Vinci, Chiara
Napoli, Nicola
Pozzilli, Paolo
Ludvigsson, Johnny
Nissim, Ahuva
Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
title Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
title_full Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
title_fullStr Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
title_full_unstemmed Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
title_short Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
title_sort antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491589/
https://www.ncbi.nlm.nih.gov/pubmed/28526919
http://dx.doi.org/10.1007/s00125-017-4296-1
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