title: Early microbial markers of celiac disease.
abstract: OBJECTIVE
  Seroreactivity against the Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) has been detected in celiac disease patients with small-bowel mucosal atrophy. Levels of these antibodies decrease during a gluten-free diet, but their functions and time of appearance in celiac disease are not known. We aimed to search for evidence of possible microbial targets of the immune responses in the early-stage celiac disease patients who showed normal small-bowel mucosal architecture at the time of the first investigations, but later on a gluten-containing diet developed mucosal atrophy.
  
  
  METHODS
  Forty-four cases with proven early-stage celiac disease and normal mucosal morphology were enrolled. Patients' sera were tested for celiac disease antibodies against tissue transglutaminase (tTG-ab), endomysium, and for microbial antibodies against I2, OmpW, and ASCA IgG and IgA isotypes in both at the time of diagnosis and while on a gluten-free diet.
  
  
  RESULTS
  Thirty-four (77%) of 44 patients with early-stage celiac disease had elevated serum antibodies to one or more of the antibodies ASCA, I2, and OmpW. Furthermore, 5 of 6 cases negative for both tTG-ab and endomysium showed positivity for the microbial markers. Seroreactivity to ASCA IgA, ASCA IgG, and OmpW decreased significantly during gluten-free diet.
  
  
  CONCLUSIONS
  Seroreactivity to different microbial antigens is evident already in patients with early-stage celiac disease. ASCA antibodies seem to be gluten-dependent. The results indicate that the microbial targets might have a role in the early development of celiac disease.
authors: *Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital §School of Health Sciences ¶School of Medicine, University of Tampere Departments of †Pediatrics ∥Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital #Seinäjoki Central Hospital, Seinäjoki **Hämeenlinna Central Hospital, Hämeenlinna, Finland ‡Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA.
authors: Liisa
authors: L
authors: Viitasalo
authors: Laura
authors: L
authors: Niemi
authors: Merja
authors: M
authors: Ashorn
authors: Sara
authors: S
authors: Ashorn
authors: Jonathan
authors: J
authors: Braun
authors: Heini
authors: H
authors: Huhtala
authors: Pekka
authors: P
authors: Collin
authors: Markku
authors: M
authors: Mäki
authors: Katri
authors: K
authors: Kaukinen
authors: Kalle
authors: K
authors: Kurppa
authors: Sari
authors: S
authors: Iltanen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000908:Antibodies, Fungal / Q000097:blood*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology*; D055050:Diet, Gluten-Free; D005260:Female; D019204:GTP-Binding Proteins; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D029701:Saccharomyces cerevisiae Proteins / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D011503:Transglutaminases / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000908:Antibodies, Fungal; D001425:Bacterial Outer Membrane Proteins; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C437325:OmpW protein, Bacteroides caccae; C469916:PfiT protein, Pseudomonas fluorescens; D029701:Saccharomyces cerevisiae Proteins; D018089:Superantigens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins