Gastroenterology

Gastroenterology

Volume 115, Issue 6, December 1998, Pages 1322-1328
Gastroenterology

Alimentary Tract
Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease,☆☆

https://doi.org/10.1016/S0016-5085(98)70008-3Get rights and content

Abstract

Background & Aims: Tissue transglutaminase has been reported to be the target for endomysial antibodies in celiac disease. We sought to establish whether immunoglobulin (Ig) A class tissue transglutaminase autoantibodies can be considered specific for celiac disease. Methods: Serum samples from 136 patients with untreated celiac disease (diagnosed according to the criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition) and 207 disease controls were studied. Enzyme-linked immunosorbent assay (ELISA) and Western blots were performed using calcium-treated and untreated tissue transglutaminase as antigen. Reticulin, endomysial, and mouse monoclonal tissue transglutaminase antibodies were studied by an indirect immunofluorescence method and gliadin antibodies with ELISA. Results: The calcium-activated tissue transglutaminase autoantibody ELISA was highly sensitive (129 of 136) and specific (194 of 207) in detecting celiac disease. The new autoantibody ELISA test correlated well with the endomysial antibody test. Tissue transglutaminase autoantibody ELISA showed a clearly better predictive potential than the IgA class gliadin antibody ELISA. Immunoblots and ELISA blocking studies showed that calcium is needed for the specific antigen-antibody reaction to occur. Double immunofluorescence staining in human umbilical cord with sera from patients with celiac disease and with monoclonal tissue transglutaminase antibodies showed complete overlap. Conclusions: Calcium-activated tissue transglutaminase autoantibody ELISA is highly accurate in detecting untreated celiac disease. Tissue transglutaminase seems to be the target self-antigen for endomysial antibodies.

GASTROENTEROLOGY 1998;115:1322-1328

Section snippets

Patients

The patients had been examined at the Departments of Pediatrics or Medicine at Tampere University Hospital and at the Children's Hospital, Helsinki University. Small bowel biopsy specimens were taken by using the Watson capsule technique or endoscopically.

Serum samples were obtained from 136 consecutive patients with untreated celiac disease (median age, 10.7 years; range 0.8–69.3) who had severe villous atrophy and crypt hyperplasia and who were on a normal diet (group I). In children, the

Tissue transglutaminase antibody ELISA test

The mean optical density for the first 20 patients with untreated celiac disease was 0.455 (95% confidence interval [CI], 0.237–0.673) and for the first 24 disease control patients 0.132 (95% CI, 0.124–0.140) tested with ELISA using tissue transglutaminase in PBS as antigen. Thus, the test seemed to distinguish celiac patients from controls. However, all sera tested had a high sample background. The optical densities without coating with tissue transglutaminase were 0.499 (95% CI, 0.209–0.789)

Discussion

In untreated celiac disease, ingested gluten triggers the production of IgA class serum tissue autoantibodies, i.e., R1-type reticulin, endomysial, and jejunal antibodies.2, 3, 17, 18, 19, 20, 21, 24 These antibodies seem to be highly specific for celiac disease, and they are directed against certain noncollagenous structures in the human extracellular matrix.25 However, the identity of the autoantigen has remained elusive. Recently, Dieterich et al.11 reported that tissue transglutaminase

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  • Cited by (0)

    Address requests for reprints to: Markku Mäki, M.D., Celiac Disease Study Group, Institute of Medical Technology, University of Tampere, P.O. Box 607, FIN-33101 Tampere, Finland. e-mail: [email protected]; fax: (358) 3-215-7746; Web site: http://www.uta.fi/~llmama/

    ☆☆

    Supported by the Foundation for Pediatric Research, Medical Research Fund of Tampere University Hospital, Medical Research Council, Academy of Finland, and Sigrid Juselius Foundation.

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