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乳糜泻患者外周血单核细胞中T-bet和磷酸化信号转导子和转录激活子1的表达:疾病活动的新标志物

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

作者信息

Frisullo G, Nociti V, Iorio R, Patanella A K, Plantone D, Bianco A, Marti A, Cammarota G, Tonali P A, Batocchi A P

机构信息

Department of Neurosciences, Catholic University, Largo Agostino Gemelli 8, Rome, Italy.

出版信息

Clin Exp Immunol. 2009 Oct;158(1):106-14. doi: 10.1111/j.1365-2249.2009.03999.x.

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.

摘要

乳糜泻(CD)被认为是一种T细胞介导的自身免疫性疾病,在未经治疗的CD患者黏膜中,已发现T-bet和磷酸化信号转导及转录激活因子(pSTAT)1(辅助性T细胞1型(Th1)细胞发育的关键转录因子)上调。通过转录因子分析,我们研究了CD患者外周血中T-bet和pSTAT1表达是否上调以及是否与疾病活动相关。我们采用流式细胞术分析了15例未经治疗和15例已治疗的CD患者以及30例对照者外周血中CD4(+)、CD8(+) T细胞、CD19(+) B细胞和单核细胞中T-bet、pSTAT1和pSTAT3的表达,并对5例乳糜泻患者饮食治疗前后进行了纵向分析。我们通过酶联免疫吸附测定(ELISA)评估外周血单核细胞(PBMC)培养物中干扰素(IFN)-γ、白细胞介素(IL)-17和IL-10的产生。未经治疗的CD患者中,CD4(+)、CD8(+) T细胞、CD19(+) B细胞和单核细胞中的T-bet表达以及PBMC产生的IFN-γ高于已治疗的CD患者和对照者。未经治疗的CD患者的CD4(+)T细胞、B细胞和单核细胞中的pSTAT1表达高于已治疗的CD患者和对照者。与已治疗的CD患者和对照者相比,未经治疗患者的单核细胞中pSTAT3仅增加。转录因子纵向评估获得的数据证实了这些结果。外周血单核细胞中pSTAT1和T-bet蛋白表达的流式细胞术分析可能是评估CD患者疾病活动和饮食治疗反应的有用且敏感的标志物。

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