Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet

Not, Tarcisio; Ziberna, Fabiana; Vatta, Serena; Quaglia, Sara; Martelossi, Stefano; Villanacci, Vincenzo; Marzari, Roberto; Florian, Fiorella; Vecchiet, Monica; Sulic, Ana Marija; Ferrara, Fortunato; Bradbury, Andrew; Sblattero, Daniele; Ventura, Alessandro

doi:10.1136/gut.2010.232900

Cited by 45 publications

(58 citation statements)

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“…Using the first approach, patients with gluten sensitivity were identified among patients with irritable bowel syndrome who presented these antibodies in intestinal fluids, but not in serum [28]. Recently, Not et al [22] have reported that a large proportion of DQ2/DQ8-positive relatives of CD patients with normal mucosa and without measurable serum levels of anti-TG2 produce these antibodies in the intestine in response to gluten. We showed that two of the three patients in the control group who secreted anti-TG2 into culture supernatants were, in one case, a first-degree relative and in the second case a patient affected by type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…These antibodies are produced at intestinal level [6], where they could be deposited even before they appear in circulation [7,20]. Two aspects can make intestinal anti-TG2 antibodies relevant: the first is their suggested ability in potential coeliac patients to predict evolution towards a clear enteropathy; the second is their possible role in revealing a condition of gluten sensitivity in patients with absence of CD-associated autoantibodies in their serum [21,22]. Therefore, it is particularly important to find the most suitable assay to detect and measure these antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is particularly important to find the most suitable assay to detect and measure these antibodies. In the last 20 years different assays have been used: measurement in faeces [23] or in intestinal fluids [24], search in supernatants of cultured biopsy fragments [11][12][13][14][15][16][17] or detection in the same biopsies of deposited antibodies [16], or expression in phage libraries of RNA, obtained from biopsies, coding for the antibodies [6,22]. Detection of anti-endomysium antibodies (EMA) and anti-TG2 IgA antibodies in faecal supernatants from CD patients was determined to be unreliable as a diagnostic test [25].…”

Section: Discussionmentioning

confidence: 99%

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Intestinal anti-tissue transglutaminase antibodies in potential coeliac disease

Tosco

Aitoro

Auricchio

et al. 2012

Clinical and Experimental Immunology

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SummaryAnti-tissue transglutaminase 2 (anti-TG2) antibodies are present in the serum of the great majority of untreated coeliac disease (CD) patients. They are produced and deposited in the small intestinal mucosa. Potential CD patients present serum anti-TG2 antibodies higher than cut-off, but a normal duodenal mucosa where mucosal deposits of anti-TG2 are not always detectable. The aim of our work was to investigate the presence of anti-TG2 intestinal antibodies in patients with potential CD, and identify the most sensitive test to detect them. Twelve active CD patients, 28 potential CD patients and 39 non-CD controls were enrolled. Biopsy fragments from all patients were analysed by double immunofluorescence to detect mucosal deposits of anti-TG2 antibodies. Fragments from the same subjects were also cultured for 24 h with medium in the presence or absence of gliadin peptides. Anti-TG2 autoantibodies secreted into supernatants were measured by enzyme-linked immunosorbent assay. All active CD, 68% of potential CD patients and 20% of non-CD controls showed mucosal deposits of immunoglobulin (Ig)A anti-TG2; at the same time 100, 96 and 8% of active CD, potential CD and non-CD control patients secreted these antibodies in culture supernatants, respectively. Our data showed that, to detect intestinal anti-TG2 antibodies, the measurement of antibodies secreted into culture supernatants has higher sensitivity and specificity (97·5 and 92·3%, respectively) than the detection of mucosal deposits (77·5 and 80·0%, respectively). The measurement of intestinal anti-TG2 antibodies may prove useful in clinical practice to predict evolution towards mucosal atrophy in potential coeliac patients and identify patients with gluten sensitivity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Intestinal anti-tissue transglutaminase antibodies in potential coeliac disease

Tosco

Aitoro

Auricchio

et al. 2012

Clinical and Experimental Immunology

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“…2,3 In this context, the anti-tTG in the intestinal mucosal seem to be the specific CD immunological marker that is detectable before the development of intestinal atrophy and the appearance of serum anti-tTG. 4 This prospective study investigates the presence of intestinal anti-tTG antibodies in patients with differing clinical spectrums of genetic gluten intolerance by using two immunoassays: double immunofluorescence test for anti-tTG on the intestinal mucosa and flow cytometry assay to measure acid-eluted intestinal anti-tTG.…”

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confidence: 99%

Intestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance

et al. 2014

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Celiac disease (CD) is an autoimmune enteropathy characterized by gluten-triggered intestinal mucosa lesions in genetically susceptible individuals carrying the HLA DQ2 or DQ8. CD diagnosis is based on the concentration of IgA serum antitransglutaminase (anti-tTG) antibodies together with mucosal damage at intestinal biopsy.1 However, it is now known that in subjects with genetic gluten intolerance, gastrointestinal and extra-intestinal symptoms may be present even when both mucosal morphology and serum anti-tTGs are normal. 2,3 In this context, the anti-tTG in the intestinal mucosal seem to be the specific CD immunological marker that is detectable before the development of intestinal atrophy and the appearance of serum anti-tTG. 4 This prospective study investigates the presence of intestinal anti-tTG antibodies in patients with differing clinical spectrums of genetic gluten intolerance by using two immunoassays: double immunofluorescence test for anti-tTG on the intestinal mucosa and flow cytometry assay to measure acid-eluted intestinal anti-tTG. In selected cases, the immunological data were compared with the corresponding mucosal phage-display assays in order to clone the anti-tTG derived from the IGHV5-51 gene. Results were correlated with the patients' clinical condition and the effects of a 24-months gluten-free diet (GFD) or gluten-containing diet (GCD).This study was conducted at the Institute of Child Health IRCCS 'Burlo Garofolo' from June 2011 to June 2013 (ClinicalTrials.gov NCT00677495) and it was approved by the Independent Ethical Committee of our Institute. In the course of gastro-intestinal endoscopy, six biopsies were obtained from each patient. All patients were tested for the presence of HLA DQ2 or DQ8 haplotypes, and measured for the concentration of serum IgA anti-tTGs. The biopsies of patients testing positive for intestinal anti-tTG antibodies but with both normal mucosa and serum anti-tTG, were analysed by phage display technology. All patients diagnosed as having CD markers were followed for their clinical condition, the concentration of serum anti-tTGs and the effects of a 24-month GFD or GCD.Serum IgA anti-TG antibodies were measured using an ELISA assay (Eurospital, Trieste, Italy) following the manufacturer's instructions (n.v.,7 U/ml). Serum IgA anti-endomysium antibodies (AEAs), HLA DQ2/8 alleles and phage IgA anti-tTG antibody libraries were evaluated as previously described.3 The histological classification of the intestinal biopsies was based on Oberhuber's criteria. 5The frozen sections were examined for the IgA anti-tTG deposits by direct double immunofluorescence as previously described.2 Briefly, the sections were incubated with a monoclonal mouse antibody against transglutaminase type-2 enzyme (CUB7402; NeoMarkers, Fremont, California, USA) to detect (in red) the transglutaminase enzyme and by fluorescein anti-human IgA rabbit antibody (Dako, Glostrup, Denmark) to detect (in green) IgA deposits. The multicolour analysis was performed by Axioplan2 Zeiss fluorescence micr...

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“…1) and that most cases present with mild mucosal changes and less antibodies. However, milder enteropathy does not mean less symptoms, as malabsorption is an inflammatory process and does not correlate with mucosal abnormalities at all (7,8). This is the reason why there are over 500.000 undiagnosed celiac patients in the United Kingdom.…”

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confidence: 99%