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Association of Pathogenic Th17 Cells with the Disease Severity and Its Potential Implication for Biological Treatment Selection in Psoriasis Patients.
Mediators of Inflammation ( IF 4.4 ) Pub Date : 2020-07-31 , DOI: 10.1155/2020/8065147
Cristina Aguilar-Flores 1 , Octavio Castro-Escamilla 1, 2 , Elizabeth M Ortega-Rocha 1, 3 , César Maldonado-García 4 , Fermín Jurado-Santa Cruz 4 , Gibrán Pérez-Montesinos 4 , Alicia Lemini-López 5 , Laura C Bonifaz 1
Affiliation  

Psoriasis is an inflammatory autoimmune disease characterized by cutaneous lesions in plaques. It has been proposed that the immune response has a key role in the disease progression. Particularly, the Th17 cells through IL-17 can contribute to maintain the inflammatory process. The pathogenic Th17 phenotype has been described in human diseases and associated with high severity in inflammatory experimental models. However, it is not clear if the pathogenic phenotype could be present in the skin and peripheral blood as well as its possible association to severity in psoriasis. In the lesional skin, we found high infiltration of Th17 cells and the pathogenic phenotype, finding a correlation between the frequency of Th17 cells and the Psoriasis Area and Severity Index (PASI) score. In peripheral blood, we observed a pool of Th17 lymphocytes with potential to acquire pathogenic features. Interestingly, the percentage of pathogenic Th17 cells (CD4+ RORγt+ IFN-γ+) correlates with disease severity. Moreover, we distinguished three groups of patients based on their IL-17/IFN-γ production by Th17 lymphocytes, which seems to be related with a dynamic or stable potential to express these cytokines. Remarkably, we evaluated the cytokine production by Th17 cells as an immunological marker for the adequate selection of biologic therapy. We found that patients analyzed by this immunological approach and treated with antibodies against IL-17 and TNFα showed great improvement depicted by reduction in PASI and Dermatology Life Quality Index (DLQI) score as well as the percentage of Body Surface Area (BSA). Altogether, our results highlight the importance of the assessment of the pathogenic phenotype in Th17 cells as an immune personalized analysis with the potential to support the therapy choice in the clinical practice.

中文翻译:

致病性Th17细胞与疾病严重程度的关联及其对银屑病患者的生物治疗选择的潜在意义。

银屑病是一种炎症性自身免疫疾病,其特征在于斑块中的皮肤损伤。已经提出免疫应答在疾病进展中具有关键作用。特别是,通过IL-17的Th17细胞可有助于维持炎症过程。Th17病原体表型已在人类疾病中描述,并在炎症实验模型中与高度严重性相关。但是,尚不清楚皮肤和外周血中是否可能存在致病表型,以及是否可能与牛皮癣的严重程度有关。在病变皮肤中,我们发现Th17细胞的高度浸润和致病表型,发现Th17细胞的频率与牛皮癣面积和严重程度指数(PASI)评分之间存在相关性。在外周血中 我们观察到了可能具有致病特征的Th17淋巴细胞池。有趣的是,致病性Th17细胞(CD4+ ROR γ+ IFN- γ +)相关因素与疾病严重程度。此外,我们根据Th17淋巴细胞产生的IL-17 /IFN- γ区分了三类患者,这似乎与表达这些细胞因子的动态或稳定潜力有关。值得注意的是,我们评估了Th17细胞产生的细胞因子,将其作为免疫标记,以选择适当的生物疗法。我们发现,患者通过这种方式免疫学分析,并与抗体抗IL-17和TNF治疗α通过降低PASI和皮肤病生活质量指数(DLQI)得分以及身体表面积(BSA)百分比,可以显示出极大的改善。总之,我们的结果突出了评估Th17细胞中致病表型作为免疫个性化分析的重要性,并有可能在临床实践中支持治疗选择。
更新日期:2020-07-31
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