TY - JOUR T1 - Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet. JF - Gut Y1 - 2011 A1 - Not, Tarcisio A1 - Ziberna, Fabiana A1 - Vatta, Serena A1 - Quaglia, Sara A1 - Martelossi, Stefano A1 - Villanacci, Vincenzo A1 - Marzari, Roberto A1 - Florian, Fiorella A1 - Vecchiet, Monica A1 - Sulic, Ana-Marija A1 - Ferrara, Fortunato A1 - Bradbury, Andrew A1 - Sblattero, Daniele A1 - Ventura, Alessandro KW - Adolescent KW - Adult KW - Antibodies, Anti-Idiotypic KW - Asymptomatic Diseases KW - Celiac Disease KW - Child KW - Child, Preschool KW - Diet, Gluten-Free KW - Fatty Acid-Binding Proteins KW - Female KW - Genetic Predisposition to Disease KW - GTP-Binding Proteins KW - Health Status KW - Humans KW - Intestinal Mucosa KW - Male KW - Middle Aged KW - Peptide Library KW - Transglutaminases KW - Young Adult AB -

BACKGROUND AND 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.

VL - 60 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21471568?dopt=Abstract ER -