@article {1741, title = {Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet.}, journal = {Gut}, volume = {60}, year = {2011}, month = {2011 Nov}, pages = {1487-93}, abstract = {

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{\textquoteright} 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{\textquoteright} 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.

}, keywords = {Adolescent, Adult, Antibodies, Anti-Idiotypic, Asymptomatic Diseases, Celiac Disease, Child, Child, Preschool, Diet, Gluten-Free, Fatty Acid-Binding Proteins, Female, Genetic Predisposition to Disease, GTP-Binding Proteins, Health Status, Humans, Intestinal Mucosa, Male, Middle Aged, Peptide Library, Transglutaminases, Young Adult}, issn = {1468-3288}, doi = {10.1136/gut.2010.232900}, author = {Not, Tarcisio and Ziberna, Fabiana and Vatta, Serena and Quaglia, Sara and Martelossi, Stefano and Villanacci, Vincenzo and Marzari, Roberto and Florian, Fiorella and Vecchiet, Monica and Sulic, Ana-Marija and Ferrara, Fortunato and Bradbury, Andrew and Sblattero, Daniele and Ventura, Alessandro} } @article {1610, title = {Gastrointestinal Foxp3 expression in normal, inflammatory and neoplastic conditions.}, journal = {Pathology}, volume = {43}, year = {2011}, month = {2011 Aug}, pages = {465-71}, abstract = {

BACKGROUND: Foxp3(+) regulatory T lymphocytes (T-regs) represent an important regulatory cell subset in inflammatory, preneoplastic and neoplastic conditions of the gastrointestinal tract.

METHODS: Inflammatory, preneoplastic and neoplastic conditions of the gastrointestinal tract (189 cases) were studied with the evaluation of Foxp3 regulatory T cells based on immunohistochemistry.

RESULTS: Few Foxp3(+) cells were found in controls and inflammatory conditions (oesophagitis, gastritis, coeliac disease, inflammatory bowel disease); in preneoplastic and neoplastic conditions the number of Foxp3(+) cells was significatively increased.

CONCLUSIONS: In normal conditions the number of mucosal lymphocytes is very low throughout the gastro-intestinal tract; in active coeliac disease patients or on a gluten-free diet, only a slight increase in Foxp3(+) cells may be found. Gastrointestinal cancers are associated with higher Foxp3(+) cell proportion, compared with microscopically normal tissue and with precancerous conditions. However, it is uncertain whether the increase in these regulatory cells is a cause or a consequence of tumour progression.

}, keywords = {Adult, Aged, Celiac Disease, Cell Count, Disease Progression, Esophagitis, Female, Forkhead Transcription Factors, Gastric Mucosa, Gastritis, Humans, Inflammatory Bowel Diseases, Lymphocytes, Male, Middle Aged, Precancerous Conditions, Stomach Diseases, Stomach Neoplasms, Young Adult}, issn = {1465-3931}, doi = {10.1097/PAT.0b013e3283485e37}, author = {Villanacci, Vincenzo and Not, Tarcisio and Nascimbeni, Riccardo and Ferrara, Fortunato and Tommasini, Alberto and Manenti, Stefania and Antonelli, Elisabetta and Bassotti, Gabrio} }