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

ABSTRACT 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.
    BMC Immunology 04/2012; 13(1):20. DOI:10.1186/1471-2172-13-20 · 2.48 Impact Factor
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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.
    Saudi Journal of Gastroenterology 08/2008; 14(3):135-8. DOI:10.4103/1319-3767.41732 · 1.12 Impact Factor
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    • "As the enhanced levels of the serum antibodies to gliadin are found in patients with celiac disease, as well as of antibodies to transglutaminase-2 (TTG-2) [4,5], to calreticulin [6,7] and Ro/SSA antigen [8], the aim of this work was the screening of MM patients' sera for their immunoreactivity to food constituent gliadin, and to autoantigens: tissue transglutaminase-2 (tTG-2) and Ro/SSA antigen, in order to assess whether immunoreactivity to mentioned antigens at least partially contributes to the immunological imbalance in multiple myeloma. "
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    ABSTRACT: Multiple myeloma (MM) is a clonal B-cell disorder with many immunological disturbances. The aim of this work was to assess whether some of food antigens contribute to the imbalance of immune response by screening the sera of MM patients for their immunoreactivity to food constituent gliadin, to tissue transglutaminase-2 (tTG-2) and to Ro/SSA antigen.Sera from 61 patients with MM in various stages of disease, before, or after some cycles of conventional therapy were analyzed by commercial Binding Site ELISA tests. The control group consisted of 50 healthy volunteers. Statistical analysis of data obtained was performed by Mann Whitney Test. The higher serum IgA immunoreactivity to gliadin was found in 14/56 patients and in one of control people. The enhanced serum IgG immunoreactivity to gliadin was found in only two of tested patients and in two controls. The enhanced IgA immunoreactivity to tTG-2 was found in 10/49 patients' sera, while 4/45 patients had higher serum IgG immunoreactivity. The enhanced serum IgG immunoreactivity to RoSSA antigen was found in 9/47 analyzed MM patients' sera. Statistical analysis of data obtained revealed that only the levels of anti-tTG-2 IgA immunoreactivity in patients with MM were significantly higher than these obtained in healthy controls (P < 0.02) Data obtained showed the existence of the enhanced serum immunoreactivity to gliadin, tTG-2 and Ro/SSA antigens in some patients with MM. These at least partially could contribute to the immunological imbalance frequently found in this disease.
    BMC Immunology 02/2008; 9(1):22. DOI:10.1186/1471-2172-9-22 · 2.48 Impact Factor
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