Abstract
Objective. To study T-helper (Th)1–Th2–Th3 gene activation profile in the small intestine and peripheral blood of children with celiac disease (CD) with special interest in the response to the gluten-free diet (GFD) treatment in order to elucidate an immune dysregulation not triggered by gluten. Material and methods. Small intestinal biopsies and venous blood were taken from seven children with CD (mean age: 8 years, four girls) at presentation and after 1 year of strict GFD. The Th1–Th2–Th3 gene expression profile was examined by real-time PCR arrays. The findings were compared with the corresponding expressions in peripheral blood and small intestinal biopsies from six reference children without CD (mean age: 6 years, four girls). Results. The Th1 gene expression profile including interferon (IFN)-γ, signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF) 1 together with reduced interleukin (IL)-2 expression was pronounced in small intestinal biopsies from children with untreated CD. A downregulation of IFN-γ transcripts was seen after 1 year of GFD, but there was still increased expression of STAT1 and IRF1 in association with low IL-2 expression in spite of eliminated exposure to wheat gluten. By contrast, the decreased intestinal expression of Th2 gene markers observed at presentation was normalized with GFD. The alterations in the mucosal gene expression profile were not reflected in peripheral blood. Conclusion. The GFD did not correct the increased activation of the IFN-γ signaling pathway related markers and reduced IL-2 expression, suggesting that they represent an immune dysregulation not dependent on gluten exposure.
Acknowledgements
We thank all children who participated in the study. Lars Stenhammar, Pia Laurin, Louise Forslund and Maria Nordwall at the Paediatric Clinics in Linköping, Norrköping and Motala are acknowledged for the clinical support. The research nurses at the Division of Paediatrics in Linköping, Norrköping and Motala and the laboratory technicians Gosia Konefal and Ingela Johansson are also thanked for their help with the sample collection. Rosaura Casas is acknowledged for her considerable input in preparation of the manuscript. This work was generously supported by the County Council of östergötland, Barndiabetesfonden and the Swedish Research Council (2008-4051).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.