title: Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet.
abstract: OBJECTIVE
  Antitransglutaminase (anti-TG2) antibodies are synthesised in the intestine and their presence seems predictive of future coeliac disease (CD). This study investigates whether mucosal antibodies represent an early stage of gluten intolerance even in the absence of intestinal damage and serum anti-TG2 antibodies.
  
  
  METHODS
  This study investigated 22 relatives of patients with CD genetically predisposed to gluten intolerance but negative for both serum anti-TG2 antibodies and intestinal abnormalities. Fifteen subjects were symptomatic and seven were asymptomatic. The presence of immunoglobulin A anti-TG2 antibodies in the intestine was studied by creating phage-antibody libraries against TG-2. The presence of intestinal anti-TG2 antibodies was compared with the serum concentration of the intestinal fatty acid-binding protein (I-FABP), a marker for early intestinal mucosal damage. The effects of a 12-month gluten-free diet on anti-TG2 antibody production and the subjects' clinical condition was monitored. Twelve subjects entered the study as controls.
  
  
  RESULTS
  The intestinal mucosa appeared normal in 18/22; 4 had a slight increase in intraepithelial lymphocytes. Mucosal anti-TG2 antibodies were isolated in 15/22 subjects (68%); in particular symptomatic subjects were positive in 13/15 cases and asymptomatic subjects in 2/7 cases (p=0.01). No mucosal antibodies were selected from the controls' biopsies. There was significant correlation between the presence of intestinal anti-TG2 antibodies and positive concentrations of I-FABP (p=0.0008). After a gluten-free diet, 19/22 subjects underwent a second intestinal biopsy, which showed that anti-TG2 antibodies had disappeared in 12/15 (p=0.002), while I-FABP decreased significantly (p<0.0001). The diet resolved both extraintestinal and intestinal symptoms.
  
  
  CONCLUSIONS
  A new form of genetic-dependent gluten intolerance has been described in which none of the usual diagnostic markers is present. Symptoms and intestinal anti-TG2 antibodies respond to a gluten free-diet. The detection of intestinal anti-TG2 antibodies by the phage-antibody libraries has an important diagnostic and therapeutic impact for the subjects with gluten-dependent intestinal or extraintestinal symptoms. Clinical trial number NCT00677495.
authors.affiliation: Istituto per l'Infanzia Burlo Garofolo, Via dell'Istria 65/1, Trieste 34100, Italy. not@burlo.trieste.it
authors.forename: Tarcisio
authors.initials: T
authors.lastname: Not
authors.forename: Fabiana
authors.initials: F
authors.lastname: Ziberna
authors.forename: Serena
authors.initials: S
authors.lastname: Vatta
authors.forename: Sara
authors.initials: S
authors.lastname: Quaglia
authors.forename: Stefano
authors.initials: S
authors.lastname: Martelossi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.forename: Roberto
authors.initials: R
authors.lastname: Marzari
authors.forename: Fiorella
authors.initials: F
authors.lastname: Florian
authors.forename: Monica
authors.initials: M
authors.lastname: Vecchiet
authors.forename: Ana-Marija
authors.initials: AM
authors.lastname: Sulic
authors.forename: Fortunato
authors.initials: F
authors.lastname: Ferrara
authors.forename: Andrew
authors.initials: A
authors.lastname: Bradbury
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ventura
mesh_terms: D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D058070:Asymptomatic Diseases; D002446:Celiac Disease / Q000175:diagnosis* / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D055050:Diet, Gluten-Free; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006304:Health Status; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D050556:Fatty Acid-Binding Proteins; D019151:Peptide Library; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins