T-bet and pSTAT-1 expression in PBMC from coeliac disease patients: new markers of disease activity

• Published in: Clinical and experimental immunology 2009-10, Vol.158 (1), p.106-114
• Main Authors: Frisullo, G, Nociti, V, Iorio, R, Patanella, A.K, Plantone, D, Bianco, A, Marti, A, Cammarota, G, Tonali, P.A, Batocchi, A.P
• Format: Article
• Language: English
• Subjects: Acute Disease; Adult; Analysis of Variance; Analytical, structural and metabolic biochemistry; Antigens, CD19 - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; Biomarkers - blood; Case-Control Studies; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; celiac disease; Celiac Disease - blood; Celiac Disease - diet therapy; coeliac disease; diet; Diet, Gluten-Free; Female; Flow Cytometry - methods; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Interferon-gamma - analysis; Interleukin-10 - analysis; Interleukin-17 - analysis; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Middle Aged; Other diseases. Semiology; STAT; STAT1 Transcription Factor - analysis; STAT3 Transcription Factor - blood; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T-bet; T-Box Domain Proteins - analysis; transcription factors; Translational Studies
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.03999.x

Coeliac disease (CD) is considered a T cell-mediated autoimmune disease, and up-regulation of T-bet and phosphorylated signal transducers and activators of transcription (pSTAT)1, key transcription factors for the development of T helper type 1 (Th1) cells, has been described in the mucosa of patients with untreated CD. Using transcription factor analysis, we investigated whether T-bet and pSTAT1 expressions are up-regulated in the peripheral blood of CD patients and correlate with disease activity. Using flow cytometry, we analysed T-bet, pSTAT1 and pSTAT3 expression in CD4⁺, CD8⁺ T cells, CD19⁺ B cells and monocytes from peripheral blood of 15 untreated and 15 treated CD patients and 30 controls, and longitudinally in five coeliac patients before and after dietary treatment. We evaluated using enzyme-linked immunosorbent assay (ELISA), interferon (FN)-γ, interleukin (IL)-17 and IL-10 production by peripheral blood mononuclear cell (PBMC) cultures. T-bet expression in CD4⁺, CD8⁺ T cells, CD19⁺ B cells and monocytes and IFN-γ production by PBMC was higher in untreated than in treated CD patients and controls. pSTAT1 expression was higher in CD4⁺T cells, B cells and monocytes from untreated than from treated CD patients and controls. pSTAT3 was increased only in monocytes from untreated patients compared with CD-treated patients and controls. The data obtained from the longitudinal evaluation of transcription factors confirmed these results. Flow cytometric analysis of pSTAT1 and T-bet protein expression in peripheral blood mononuclear cells could be useful and sensible markers in the follow-up of CD patients to evaluate disease activity and response to dietary treatment.