title: The effect of gluten-free diet on Th1-Th2-Th3-associated intestinal immune responses in celiac disease.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Paediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. anne.lahdenpera@liu.se
authors.forename: Anne
authors.initials: A
authors.lastname: Lahdenperä
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: Karin
authors.initials: K
authors.lastname: Fälth-Magnusson
authors.forename: Lotta
authors.initials: L
authors.lastname: Högberg
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002446:Celiac Disease / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology*; D002648:Child; D055050:Diet, Gluten-Free; D005260:Female; D015870:Gene Expression; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; C103024:GLMN protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D050856:Interferon Regulatory Factor-1; D020382:Interleukin-18; D007376:Interleukin-2; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; D050882:CREB-Binding Protein; C494363:CREBBP protein, human