title: Seroreactivity against Specific L5P Antigen from Mycobacterium avium subsp. paratuberculosis in Children at Risk for T1D.
abstract: OBJECTIVE
  Although numerous environmental agents have been investigated over the years as possible triggers of type 1 diabetes (T1D), its causes remain unclear. We have already demonstrated an increased prevalence of antibodies against peptides derived from Mycobacterium avuim subsp. paratuberculosis (MAP) homologous to human zinc transporter 8 protein (ZnT8) and proinsulin in Italian subjects at risk for or affected by T1D. In this study, we compared titers of the previously detected antibodies with seroreactivity to MAP lipopentapetide (L5P) that recently emerged as a strong immunogenic component able to specifically distinguish MAP from other mycobacteria.
  
  
  METHODS
  Plasma of 32 children and youth at risk for T1D including follow-up samples and 42 age-matched healthy controls (HC) recruited at the Tor Vergata University Hospital in Rome was analyzed by indirect ELISA for the presence of antibodies against MAP-derived epitopes MAP3865c133-141, MAP3865c125-133, MAP2404c70-85 and MAP1,4αgbp157-173 along with their ZnT8 and proinsulin homologs. The data were analyzed through two-tailed Mann-Whitney U test and relation between variables was determined by principal component analysis.
  
  
  RESULTS
  Responses to L5P were not detectable in subjects whose initial seroreactivity to MAP peptides and their human homologs was lost in follow-up samples, whereas anti-L5P antibodies appeared constantly in individuals with a stable immunity against MAP antigens. The overall coincidence in positivity to L5P and the four MAP epitopes both in children at risk for T1D and HC exceeded 90%.
  
  
  CONCLUSIONS
  MAP-derived homologs may cross-react with ZnT8 and proinsulin peptides inducing immune responses at a young age in subjects predisposed for T1D. Thus, L5P may have a diagnostic value to immediately indicate the presence of anti-MAP seroreactivity when evaluation of a more complex antibody status is not required. Almost complete coincidence in responses to both types of antigens lends support to the involvement of MAP in T1D.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Niegowska
authors.affiliation: Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133, Rome, Italy.
authors.forename: Novella
authors.initials: N
authors.lastname: Rapini
authors.affiliation: UMR1282, Infectiologie et Santé Publique (ISP-311), INRA Centre Val de Loire, F-37380, Nouzilly, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Biet
authors.affiliation: Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Piccinini
authors.affiliation: Institut Pasteur, Unité de Chimie des Biomolécules, Département de Biologie Structurale et Chimie, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bay
authors.affiliation: Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lidano
authors.affiliation: Pediatric Diabetology Unit, Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133, Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Manca Bitti
authors.affiliation: Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Sechi