Clinical ResearchThe gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides☆,☆☆
Section snippets
Children with CD
Twenty-six white CD patients were included in the present study. Their age at diagnosis (first small bowel biopsy) was between 1 and 12 years old (average age 4.0 years ± 2.5; 1 year old, 4 patients; 2 years old, 3 patients; 3 years old, 9 patients; 4 years old, 6 patients; 6 years old, 2 patients; 9 years old, 1 patient; 12 years old, 1 patient). In addition, biopsies of 4 adult CD patients were obtained. Only DQ2 (DQA1*0501/DQB1*02) positive patients with a confirmed diagnosis of CD have been
Establishment of GLU-specific T-cell lines from pediatric CD patients
T-cell biopsies were collected from young patients that were suspected of CD as indicated by typical clinical symptoms and/or a positive anti-endomysium test. Individual biopsies were cultured with either a trypsin/pepsin digest of GLU (termed GLU hereafter) or the same preparation that had additionally been treated with tTG (termed tTG-GLU hereafter). After 5 days, IL-2 was added and cultures that showed evidence of T-cell proliferation were expanded and tested for specificity in a
Discussion
It is generally accepted that CD is caused by uncontrolled T-cell responses to GLU peptides that are presented by HLA-DQ2 and/or -DQ8 molecules. In recent years, 5 GLU peptides have been identified that stimulate TCCs derived from small intestinal biopsies of CD patients.12, 13, 15, 16, 18 An important breakthrough has been the demonstration that deamidation of the GLU peptides by the enzyme tTG is either required for, or enhances, T-cell recognition of 4 of these peptides.12, 13, 14, 15, 16, 17
Acknowledgements
The authors thank Drs. C. Csizmadia and J. Schweizer for generous help in obtaining patient samples and Drs. B.O. Roep and R.R.P. de Vries for critically reading the manuscript.
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Address requests for reprints to: Frits Koning, Ph.D., Department of Immunohematology and Blood Transfusion, E3-Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. e-mail: [email protected]; fax: (31) 71-5216751.
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Supported by the European Community project no. BMH CT-98, a grant from the Dutch Digestive Disease Foundation (WS 98-24) and the University of Leiden.