Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies

As numerous studies put in evidence the increasing incidence of type 1 diabetes (T1D) in children, an early diagnosis is of great importance to define correct treatment and diet. Currently, the identification of classical islet autoantibodies is the primary biomarker for diagnosis in subjects at ris...

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Main Authors: Magdalena Niegowska, Daniela Paccagnini, Carla Mannu, Clara Targhetta, Marco Songini, Leonardo A. Sechi
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2016/5842701
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author Magdalena Niegowska
Daniela Paccagnini
Carla Mannu
Clara Targhetta
Marco Songini
Leonardo A. Sechi
author_facet Magdalena Niegowska
Daniela Paccagnini
Carla Mannu
Clara Targhetta
Marco Songini
Leonardo A. Sechi
author_sort Magdalena Niegowska
collection DOAJ
description As numerous studies put in evidence the increasing incidence of type 1 diabetes (T1D) in children, an early diagnosis is of great importance to define correct treatment and diet. Currently, the identification of classical islet autoantibodies is the primary biomarker for diagnosis in subjects at risk, especially in pediatric patients. Recent studies suggest that detection of antibodies against ZnT8 protein in preclinical phase can predict the development of T1D. We previously demonstrated a significant association of Mycobacterium avium subspecies paratuberculosis (MAP) with T1D in adult Sardinian patients. To enforce this finding, we investigated the presence of antibodies against ZnT8 and proinsulin (PI) with respective homologous epitopes: MAP3865c133–141/ZnT8186–194, MAP3865c125–133/ZnT8178–186, MAP2404c70–85/PI46–61, and MAP1,4αgbp157–173/PI64–80, in 23 children at risk for T1D, formerly involved in the TRIGR study, and 22 healthy controls (HCs). Positivity to anti-MAP and homologous human peptides was detected in 48% of at-risk subjects compared to 5,85% HCs, preceding appearance of islet autoantibodies. Being MAP easily transmitted to humans with infected cow’s milk and detected in retail infant formulas, MAP epitopes could be present in extensively hydrolyzed formula and act as antigens stimulating β-cell autoimmunity.
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spelling doaj-art-7626c093418842889f05f4ae0de6b2792025-02-03T06:07:32ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/58427015842701Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet AntibodiesMagdalena Niegowska0Daniela Paccagnini1Carla Mannu2Clara Targhetta3Marco Songini4Leonardo A. Sechi5Department of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyCentre for the Treatment of Complications of Diabetes, Hospital “G. Brotzu”, 09134 Cagliari, ItalyCentre for the Treatment of Complications of Diabetes, Hospital “G. Brotzu”, 09134 Cagliari, ItalyCentre for the Treatment of Complications of Diabetes, Hospital “G. Brotzu”, 09134 Cagliari, ItalyDepartment of Biomedical Sciences, University of Sassari, 07100 Sassari, ItalyAs numerous studies put in evidence the increasing incidence of type 1 diabetes (T1D) in children, an early diagnosis is of great importance to define correct treatment and diet. Currently, the identification of classical islet autoantibodies is the primary biomarker for diagnosis in subjects at risk, especially in pediatric patients. Recent studies suggest that detection of antibodies against ZnT8 protein in preclinical phase can predict the development of T1D. We previously demonstrated a significant association of Mycobacterium avium subspecies paratuberculosis (MAP) with T1D in adult Sardinian patients. To enforce this finding, we investigated the presence of antibodies against ZnT8 and proinsulin (PI) with respective homologous epitopes: MAP3865c133–141/ZnT8186–194, MAP3865c125–133/ZnT8178–186, MAP2404c70–85/PI46–61, and MAP1,4αgbp157–173/PI64–80, in 23 children at risk for T1D, formerly involved in the TRIGR study, and 22 healthy controls (HCs). Positivity to anti-MAP and homologous human peptides was detected in 48% of at-risk subjects compared to 5,85% HCs, preceding appearance of islet autoantibodies. Being MAP easily transmitted to humans with infected cow’s milk and detected in retail infant formulas, MAP epitopes could be present in extensively hydrolyzed formula and act as antigens stimulating β-cell autoimmunity.http://dx.doi.org/10.1155/2016/5842701
spellingShingle Magdalena Niegowska
Daniela Paccagnini
Carla Mannu
Clara Targhetta
Marco Songini
Leonardo A. Sechi
Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies
Journal of Diabetes Research
title Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies
title_full Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies
title_fullStr Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies
title_full_unstemmed Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies
title_short Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies
title_sort recognition of znt8 proinsulin and homologous map peptides in sardinian children at risk of t1d precedes detection of classical islet antibodies
url http://dx.doi.org/10.1155/2016/5842701
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