title: Loss and Gain of Tolerance to Pancreatic Glycoprotein 2 in Celiac Disease.
abstract: BACKGROUND
  Autoantibodies against pancreatic secretory-granule membrane glycoprotein 2 (GP2) have been demonstrated in patients with Crohn's disease but recently also with celiac disease (CD). Both entities are characterized by intestinal barrier impairment with increased gut permeability. Pathophysiological hallmark of CD is a permanent loss of tolerance to alimentary gliadin and a transient loss of tolerance to the autoantigen human tissue transglutaminase (tTG). Therefore, we explored the behavior of loss of tolerance to GP2 reported in CD.
  
  
  METHODS
  We assessed prevalences and levels of autoantibodies against GP2, CD-specific antibodies to endomysial antigens and tTG as well as Crohn's disease-specific anti-Saccharomyces cerevisiae antibodies in sera of 174 patients with active CD, 84 patients under gluten-free diet (GFD) and 129 controls. Furthermore, we looked for an association between anti-GP2 antibody positivity and degree of mucosal damage in CD.
  
  
  RESULTS
  We found significantly elevated anti-GP2 IgA positivity in active CD patients (19.5%) compared to CD patients under GFD (0.0%) and controls (5.4%, p < 0.001, respectively). Anti-GP2 IgA levels correlated significantly with CD-specific antibodies (p < 0.001). Anti-GP2 autoantibody positivity disappeared under GFD similarly to CD-specific autoantibodies against tTG and endomysial antigens. For the first time, IgA antibody levels to GP2 are demonstrated to be associated with degree of villous atrophy according to Marsh classification.
  
  
  CONCLUSIONS
  Anti-GP2 IgA seems to be associated with disease activity in a distinct subgroup of patients with CD. The observed loss of tolerance to GP2 in a subset of patients with CD is transient and disappears under GFD.
authors.affiliation: Children's Hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Laass
authors.affiliation: Institute of Immunology, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Röber
authors.affiliation: Institute for Medical Informatics and Biometry, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Range
authors.affiliation: Children's Hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Noß
authors.affiliation: GA Generic Assays GmbH, 15827 Dahlewitz/Berlin, Germany; Faculty of Science, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Roggenbuck
authors.affiliation: Institute of Immunology, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Conrad
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002446:Celiac Disease / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D055050:Diet, Gluten-Free; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D015995:Prevalence; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012441:Saccharomyces cerevisiae / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; C072961:glycoprotein-2, pancreas; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins