Troncone R, Maurano F, Rossi M, et al. IgA antibodies to tissue transglutaminase: an effective diagnostic test for celiac disease

From the Department of Pediatrics, University Federico II, Naples, Italy
Journal of Pediatrics (Impact Factor: 3.79). 03/1999; 134(2):166-171. DOI: 10.1016/S0022-3476(99)70410-5


Objective: Tissue transglutaminase (tTG) is the main autoantigen recognized by endomysial antibodies. The aim of this study was to assess sensitivity, specificity, and predictive value of IgA and IgG antibodies to tTG in the diagnosis of celiac disease compared with endomysial antibodies. Study design: We established enzyme-linked immunosorbent assay procedures to measure IgA and IgG antibodies to tTG in sera from 48 untreated and 33 treated patients with celiac disease and from 63 patients with gastrointestinal disease who were in a control group. Sera from 10 patients with celiac disease were examined at various times after gluten was reintroduced into the patients’ diet. Results: Both IgA and IgG to tTG were significantly (P < .001) higher in serum of untreated patients with celiac disease versus those in the control group; IgA but not IgG was significantly (P < .001) higher in untreated versus treated patients with celiac disease. IgA and IgG antitissue tTG had a diagnostic sensitivity, specificity, and positive predictive value of 92% and 21%, 98% and 97%, and 98% and 83%, respectively. The concordance rate of IgA anti-tTG with IgA antiendomysial antibodies was 95%. In 5 of the 10 patients undergoing gluten challenge, IgA antiendomysium antibodies were detected earlier than IgA anti-tTG antibodies. Conclusions: tTG-based enzyme-linked immunosorbent assay is an effective diagnostic test, although immunofluorescent-based assays are more sensitive, particularly during gluten challenge. (J Pediatr 1999;134:166-71)

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    • "Although the enzymatic activity of TG-2 and, to some extent, its physiological roles in ECM stabilisation, apoptosis and interactions between cells and the ECM are well-established, less is known about its interactions with pathological processes [9]. TG-2 has previously been identified as an autoantigen in coeliac disease [11] and antibodies directed against it can be detected as the basis of a diagnostic test for coeliac disease [34]. TG-2 is found in the small intestinal submucosa of both healthy subjects and also those with coeliac disease, and levels of it are elevated in the small intestine of those with coeliac disease [12]. "
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    ABSTRACT: Dendritic cells (DCs) are part of the innate immune system with a key role in initiating and modulating T cell mediated immune responses. Coeliac disease is caused by inappropriate activation of such a response leading to small intestinal inflammation when gluten is ingested. Tissue transglutaminase, an extracellular matrix (ECM) protein, has an established role in coeliac disease; however, little work to date has examined its impact on DCs. The aim of this study was to investigate the effect of small intestinal ECM proteins, fibronectin (FN) and tissue transglutaminase 2 (TG-2), on human DCs by including these proteins in DC cultures. The study used flow cytometry and scanning electron microscopy to determine the effect of FN and TG-2 on phenotype, endocytic ability and and morphology of DCs. Furthermore, DCs treated with FN and TG-2 were cultured with T cells and subsequent T cell proliferation and cytokine profile was determined. The data indicate that transglutaminase affected DCs in a concentration-dependent manner. High concentrations were associated with a more mature phenotype and increased ability to stimulate T cells, while lower concentrations led to maintenance of an immature phenotype. These data provide support for an additional role for transglutaminase in coeliac disease and demonstrate the potential of in vitro modelling of coeliac disease pathogenesis.
    Full-text · Article · Apr 2012 · BMC Immunology
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    • "The advantages of tTG testing is that the ELISA test eliminates the disadvantages associated with the use of EMA, namely the higher cost, time-consuming protocol which is unsuitable for testing large numbers of samples, the use of monkey esophagus (or human umbilical cord), and the subjective interpretation of the immunofluorescence analysis[15]. Several studies have compared the analytical and clinical utility of commercially available antitransglutaminase ELISAs assays596061626364656667686970717273, and found that the use of tTG as antigen for CD diagnosis presents an adequate sensitivity and specificity. Therefore, major efforts have been concentrated on developing a tTG-based ELISA, using either the commercially available guinea pig tTG or human recombinant tTG. "
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    ABSTRACT: Celiac disease (CD) is an autoimmune enteropathy, characterized by an inappropriate T-cell-mediated immune response to the ingestion of certain dietary cereal proteins in genetically susceptible individuals. This disorder presents environmental, genetic, and immunological components. CD presents a prevalence of up to 1% in populations of European ancestry, yet a high percentage of cases remain underdiagnosed. The diagnosis and treatment should be made early since untreated disease causes growth retardation and atypical symptoms, like infertility or neurological disorders. The diagnostic criteria for CD, which requires endoscopy with small bowel biopsy, have been changing over the last few decades, especially due to the advent of serological tests with higher sensitivity and specificity. The use of serological markers can be very useful to rule out clinical suspicious cases and also to help monitor the patients, after adherence to a gluten-free diet. Since the current treatment consists of a life-long gluten-free diet, which leads to significant clinical and histological improvement, the standardization of an assay to assess in an unequivocal way gluten in gluten-free foodstuff is of major importance.
    Full-text · Article · Jul 2010 · Analytical and Bioanalytical Chemistry
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    • "Anti-tTG antibodies are highly sensitive (95%) and specific (94%) for the diagnosis of CD.[2627] The diagnostic accuracy of anti-tTG immunoassays has been improved further by the use of human tTG instead of the nonhuman tTG preparations used in earlier immunoassay kits and up to 100% positive predictive value was also reported.[2829] "
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    ABSTRACT: This study was performed to evaluate the prevalence of celiac disease (CD) in Shiraz, southern Iran. Serum samples were collected from 1440 persons (age range = 20-83 years, mean age = 45.4 years) in 2004 and screened for endomysial and tissue transglutaminase antibodies. A questionnaire was completed for all subjects in relation to gastrointestinal (GI) symptoms and cases with positive serology were requested to undergo small-bowel biopsy. Seven cases (0.5%) were positive for IgA anti-tissue transglutaminase (anti-tTG), and only two (0.14%) were positive for IgA anti-endomysial antibody (anti-EMA), both of whom had highly positive anti-tTg levels (40.4 and 48.0 IU/l). The major clinical symptoms of CD, such as recurrent abdominal pain and change in bowel habits were present in all patients with positive anti-tTG assays. Only five subjects with positive serology agreed to undergo upper GI endoscopy and duodenal biopsy. Three of these cases were reported with Marsh I histologic findings, while in the two cases with positive serologic anti-EMA, more advanced forms of CD were present. The prevalence of CD in apparently healthy adults was lower than the reported series from northern parts of the country; therefore, we suggest a more long-term follow-up study in high-risk groups, especially in the apparently healthy subjects in our region.
    Full-text · Article · Aug 2008 · Saudi Journal of Gastroenterology
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