Zinc Transporter 8 and MAP3865c Homologous Epitopes Are Recognized at T1D Onset in Sardinian Children

PLoS One. 2013 May 17;8(5):e63371. doi: 10.1371/journal.pone.0063371. Print 2013.

Abstract

Our group has recently demonstrated that Mycobacterium avium subspecies paratuberculosis (MAP) infection significantly associates with T1D in Sardinian adult patients. Due to the potential role played by MAP in T1D pathogenesis, it is relevant to better characterize the prevalence of anti-MAP antibodies (Abs) in the Sardinian population, studying newly diagnosed T1D children. Therefore, we investigated the seroreactivity against epitopes derived from the ZnT8 autoantigen involved in children at T1D onset and their homologous sequences of the MAP3865c protein. Moreover, sera from all individuals were tested for the presence of Abs against: the corresponding ZnT8 C-terminal region, the MAP specific protein MptD, the T1D autoantigen GAD65 and the T1D unrelated Acetylcholine Receptor. The novel MAP3865c281-287 epitope emerges here as the major C-terminal epitope recognized. Intriguingly ZnT8186-194 immunodominant peptide was cross-reactive with the homologous sequences MAP3865c133-141, strengthening the hypothesis that MAP could be an environmental trigger of T1D through a molecular mimicry mechanism. All eight epitopes were recognized by circulating Abs in T1D children in comparison to healthy controls, suggesting that these Abs could be biomarkers of T1D. It would be relevant to investigate larger cohorts of children, followed over time, to elucidate whether Ab titers against these MAP/Znt8 epitopes wane after diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Bacterial / blood*
  • Autoantibodies / blood*
  • Autoantigens / immunology
  • Bacterial Proteins / immunology*
  • Cation Transport Proteins / immunology*
  • Child
  • Child, Preschool
  • Cross Reactions
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / microbiology
  • Epitope Mapping
  • Epitopes / immunology
  • Female
  • Humans
  • Italy
  • Male
  • Mycobacterium avium subsp. paratuberculosis / immunology*
  • Zinc Transporter 8

Substances

  • Antibodies, Bacterial
  • Autoantibodies
  • Autoantigens
  • Bacterial Proteins
  • Cation Transport Proteins
  • Epitopes
  • SLC30A8 protein, human
  • Zinc Transporter 8

Grant support

This research was supported by the Sardinian Region L.R.7 2009 and 2010: Progetti di ricerca di base; PRIN MIUR Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale Protocollo: 2009ZYECWZ and Italian Minister of Health, “Finalized Research” Protocollo: RF-2009-1545765, to LAS; and by the Fondazione Banco di Sardegna for Speranza Masala. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.