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ObjectiveWe aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.DesignThe study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.ResultsCohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.ConclusionOur results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Introduction Intestinal epithelial cell damages generated by inflammation in coeliac disease (CD) ranges from sub-microscopic to severe architectural distortion. Translation of quantitative morphological changes in intestinal microorgans, like villus/crypt transformation, distribution of inflammatory cells and diagnostic cut offs, is lacking for CD and gluten related micro-enteropathies. Method Investigators from 22 centres, 9 countries of 4 continents, recruited CD patients with Marsh 0-II histology (n=299), NCGS (n=151), and 262 controls. Based on an agreed protocol, epithelial morphology including intraepithelial lymphocyte (IEL) density, villus height and crypt depth were measured in well-oriented duodenal biopsies. Results In total 712 subjects were recruited from Australia (20), Finland (20), India (25), Iran (37), Italy (246), Romania (10), Turkey (30), UK (166) and USA (158). Preliminary analyses showed raw IEL density (IEL/100EC) was poorly correlated with tTG, villus height, crypt depth or their ratios, and even significant findings did not show strong correlation coefficients ( Conclusion The most specific and strongest biomarker for CD with microenteropathy is serology acting as the gold standard in this group. Villus height and crypt depth would serve as complementary tools in diagnosis of mild CD and NCGS patients. NCGS seem to have a milder morphological change compared to CD even when they present with similar Marsh scores. This study also confirms the cut off of IEL for CD with microenteropathy is similar to CD with severe enteropathy at 25 IEL/100EC.

A 21-year-old woman presented with a 2-week history of vomiting, diarrhoea and epigastric pain, with 9 kg weight loss over the last two months. Laboratory tests were normal with negative coeliac serology. Duodenal biopsies revealed total villous atrophy, crypt hypertrophy and intraepithelial lymphocytosis. A diagnosis of seronegative coeliac disease was made, and she started a gluten-free diet. However, she did not respond and her weight fell to 30.6 kg (body mass index 11), becoming dependent on parenteral nutrition. Her diagnosis was reconsidered and the histology reviewed. The histopathological features were of severe active chronic duodenitis. By diagnosis of exclusion, with the absence of other clear pathology, she was treated as Crohn’s disease. She responded to third-line therapy with biologics. In this case, the patient had refractory villous atrophy and the mucosal features, in addition to response with anti-tumour necrosis factor therapy, suggest inflammatory bowel disease, although not with complete diagnostic certainty.