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Prediction of clinical and mucosal severity of celiac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
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2010 (English)In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 2, 140-146 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: We analysed whether the quantification of autoantibodies against tissue transglutaminase could be used to predict mucosal destruction and disease severity in patients with gluten sensitivity. Patients and Methods: One hundred seventy patients with coeliac disease (CD), comprising 52 children with severe malabsorption (group 1), 59 children with mild symptoms (group II), 59 adults (group III), 134 patients with dermatitis herpetiformis (DH), and 131 disease controls, were studied. Serial serum samples of patients in groups I and II on a gluten-free diet were also included. Serum levels of antibodies against recombinant tissue transglutaminase were determined with ELISA using standard curves for quantification of antibodies. Results: Immunoglobulin (Ig)A antibodies against tissue transglutaminase (IgA-TGA) were detected in all of the patients with CD and in 95% of the DH patients. The IgA-TGA and IgG-TGA levels were higher in group I (P < 0.001). The IgG-TGA levels and positivity rate in group I (100%)were higher than in group II (81%), group III (73%), and the DH group (67%). Elevated IgA-TGA and IgG-TGA levels in combination predicted a more severe small intestinal atrophy (P < 0.0001) with a specificity of 99% for Marsh IIIb-IIIc (flat) lesions. The kinetics of the IgA-TGA decrease during diet differed between groups I and II. Conclusions: High levels of IgA-TGA and IgG-TGA antibodies were associated with the grade of mucosal villous atrophy and a more severe clinical presentation. The combined measurement of IgA-TGA and IgG-TGA enables a noninvasive prediction of small intestinal villous atrophy with high accuracy, and may reduce the need for a biopsy in patients with suspected CD.

Place, publisher, year, edition, pages
2010. Vol. 50, no 2, 140-146 p.
Keyword [en]
coeliac disease, dermatitis herpetiformis, IgA autoantibodies, IgG autoantibodies, tissue transglutaminase, transglutaminase type 2
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-96690DOI: 10.1097/MPG.0b013e3181a81384ISI: 000273994000007OAI: oai:DiVA.org:uu-96690DiVA: diva2:171347
Available from: 2008-02-06 Created: 2008-02-06 Last updated: 2016-02-25
In thesis
1. The Significance of IgG Antibodies against Tissue Transglutaminase in Coeliac Disease
Open this publication in new window or tab >>The Significance of IgG Antibodies against Tissue Transglutaminase in Coeliac Disease
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Coeliac disease (CD) is a multifactorial disease of the small intestine. In genetically predisposed individuals the, ingestion of cereals leads to a remodulation of the mucosal architecture, and the production of autoantibodies against tissue transglutaminase (tTG). The treatment is a lifelong gluten-free diet.

The diagnostic procedure relies on the examination of a small-bowel biopsy that displays villous atrophy. A spectrum of clinical manifestations is associated with CD, ranging from overt enteropathy to atypical and silent symptoms. Approximately 1% of the general population has CD, and the majority is undiagnosed. Although most patients with active CD can be detected by the assessment of elevated IgA-tTG, some patients lack these antibodies. Moreover, individuals with IgA-deficiency cannot be identified by means of IgA serology.

The aim of this thesis was to investigate the clinical utility of IgG-tTG for the detection and follow-up of subjects with active CD. The included studies showed that IgG-tTG was highly prevalent in IgA-deficient and IgA-competent patients with CD, whereas non-CD patients rarely had these antibodies. During a gluten-free diet, IgG-tTG decreased, demonstrating that IgG-tTG can be used to follow the patient’s adherence such a diet. Furthermore, 10% of healthy IgA deficient blood donors had elevated IgG-tTG, indicating that they had silent CD.

In IgA-competent subjects, high IgG-tTG levels correlated with a severe mode of CD and profound mucosal deterioration, suggesting that IgG-tTG might be involved in the disease progression. Moreover, we found that although a considerable percentage of IgA-competent patients lack IgG-tTG, the presence of these antibodies in conjunction with high levels of IgA-tTG was highly predictive of a severe small-intestine villous atrophy. It was also demonstrated that IgG-tTG normalisation coincided with clinical remission in IgA-competent CD patients on a gluten-free diet.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 56 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 307
Immunology, Coeliac disease, Tissue transglutaminase, Endomysium, IgG antibodies, Immunologi
urn:nbn:se:uu:diva-8424 (URN)978-91-554-7078-4 (ISBN)
Public defence
2008-02-27, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, 13:15
Available from: 2008-02-06 Created: 2008-02-06Bibliographically approved

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