title: T-bet and pSTAT-1 expression in PBMC from coeliac disease patients: new markers of disease activity.
abstract: 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)-gamma, 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-gamma 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.
authors.affiliation: Department of Neurosciences, Catholic University, Largo Agostino Gemelli 8, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Frisullo
authors.forename: V
authors.initials: V
authors.lastname: Nociti
authors.forename: R
authors.initials: R
authors.lastname: Iorio
authors.forename: A K
authors.initials: AK
authors.lastname: Patanella
authors.forename: D
authors.initials: D
authors.lastname: Plantone
authors.forename: A
authors.initials: A
authors.lastname: Bianco
authors.forename: A
authors.initials: A
authors.lastname: Marti
authors.forename: G
authors.initials: G
authors.lastname: Cammarota
authors.forename: P A
authors.initials: PA
authors.lastname: Tonali
authors.forename: A P
authors.initials: AP
authors.lastname: Batocchi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002446:Celiac Disease / Q000097:blood* / Q000178:diet therapy; D055050:Diet, Gluten-Free; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D020381:Interleukin-17 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D050794:STAT1 Transcription Factor / Q000032:analysis*; D050796:STAT3 Transcription Factor / Q000097:blood; D020825:T-Box Domain Proteins / Q000032:analysis*; D000098815:T-bet Transcription Factor
chemical_list: D018941:Antigens, CD19; D015415:Biomarkers; D020381:Interleukin-17; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016753:Interleukin-10; D007371:Interferon-gamma