Coeliac disease: Clinical and immunological aspects
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
A better immunological definition of coeliac disease and highly discriminatory serum markers are needed to identify children with early mucosal lesions and for rapid follow-up and a better knowledge of antigen reactivity and cytokine production will be needed to clarify the pathogenic mechanisms.
The numbers of circulating IgAanti-gliadin antibody-producing (IgAAGA SFC) cells were increased in patients with untreated coeliac disease compared to controls and treated coeliac disease patients. In children with coeliac disease the numbers of IgAAGA SFC increased rapidly after gluten challenge. The levels of IgA specific for human as well as guinea-pig tissue transglutaminase (tTG) were increased in the untreated coeliac diseasechildren compared to the control groups. A human erythrocyte tTG ELISAassay had the highest sensitivity (100%) and a specificity of 98%.
The numbers of IFN-γ producing cells in the peripheral blood was increased in children with untreated celiac disease as compared to healthy controls. The IL-4 production correlated with the serum levels of total IgE. The numbers of IFN-γ producing cells increased after gluten challenge, whereas no such change was evident for IL-4 or IL-10 producing cells. Children with coeliac disease had more mononuclear cells expressing TGF-β1, TNF-αand IFN-γ in the lamina propria as compared to disease controls. TGFβ3 and IL-4 expressing cells were present in the lamina propria as well as in the epithelial layer in children with coeliac disease.
In conclusion, our results indicate that: (1) the ELISPOT assay or other methods for detection of antibody production may be helpful in assessing the optimal timing of the biopsy to shorten the duration of gluten challenge, (2) anti-tTG IgA antibodies can be used as a sensitive and specific complement to existing serological tests for coeliac disease, (3) circulating mononuclear cells in children with active coeliac disease secrete cytokines compatible with a type 1 response, (4) mononuclear cells in the gut of children with activecoeliac disease produce type 1 cytokines as well asTGF-β and IL-4.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1999. , 52 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 839
Oncology, Coeliac disease, cytokines, TGF-beta, tissue transglutaminase, IL-4, IFN-gamma, TNF-alpha, ELISPOT, anti-endomysiumantibodies, anti-gliadin antibodies
Cancer and Oncology
Research subject Clinical Immunology
IdentifiersURN: urn:nbn:se:uu:diva-322ISBN: 91-554-4455-5OAI: oai:DiVA.org:uu-322DiVA: diva2:162255
1999-05-07, Skoogsalen, ingång 78, Akademiska sjukhuset, Uppsala, Uppsala, 13:15