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

Abstract

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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  • Authors+Show Affiliations

    ,

    Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.

    ,

    Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.

    ,

    Centre for the Treatment of Complications of Diabetes, Hospital "G. Brotzu", 09134 Cagliari, Italy.

    ,

    Centre for the Treatment of Complications of Diabetes, Hospital "G. Brotzu", 09134 Cagliari, Italy.

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    Centre for the Treatment of Complications of Diabetes, Hospital "G. Brotzu", 09134 Cagliari, Italy.

    Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.

    Source

    Journal of diabetes research 2016: 2016 pg 5842701

    MeSH

    Age Factors
    Antibodies, Bacterial
    Antibody Specificity
    Antigens, Bacterial
    Autoantibodies
    Biomarkers
    Case-Control Studies
    Cation Transport Proteins
    Child
    Child, Preschool
    Cross Reactions
    Diabetes Mellitus, Type 1
    Early Diagnosis
    Epitopes
    Humans
    Infant
    Infant, Newborn
    Islets of Langerhans
    Italy
    Mycobacterium avium subsp. paratuberculosis
    Predictive Value of Tests
    Proinsulin
    Zinc Transporter 8

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26824044

    Citation

    Niegowska, Magdalena, et al. "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, vol. 2016, 2016, p. 5842701.
    Niegowska M, Paccagnini D, Mannu C, et al. Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies. J Diabetes Res. 2016;2016:5842701.
    Niegowska, M., Paccagnini, D., Mannu, C., Targhetta, C., Songini, M., & Sechi, L. A. (2016). 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, 2016, p. 5842701. doi:10.1155/2016/5842701.
    Niegowska M, et al. Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies. J Diabetes Res. 2016;2016:5842701. PubMed PMID: 26824044.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies. AU - Niegowska,Magdalena, AU - Paccagnini,Daniela, AU - Mannu,Carla, AU - Targhetta,Clara, AU - Songini,Marco, AU - Sechi,Leonardo A, Y1 - 2015/12/28/ PY - 2015/09/17/received PY - 2015/11/09/revised PY - 2015/11/10/accepted PY - 2016/1/30/entrez PY - 2016/1/30/pubmed PY - 2016/10/25/medline SP - 5842701 EP - 5842701 JF - Journal of diabetes research JO - J Diabetes Res VL - 2016 N2 - 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. SN - 2314-6753 UR - https://www.unboundmedicine.com/medline/citation/26824044/full_citation L2 - https://dx.doi.org/10.1155/2016/5842701 DB - PRIME DP - Unbound Medicine ER -