Ludmiła Szewczak, Maja Machcińska, Magdalena Kierasińska, Urszula Zawadzka-Więch, Marta Maruszewska-Cheruiyot, Paweł Majewski, Anna Karlińska, Rafał Rola, Katarzyna Donskow-Łysoniewska
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引用次数: 0
摘要
复发性多发性硬化症与免疫细胞中Jak/STAT通路的变化有关,但人们对疾病调节药物对这些通路的影响知之甚少。本研究的目的是评估用于治疗 RRMS 的一线疾病调节药物对血液中 STAT 通路和 T 细胞相关基因的表达、女性血清中 sgp130 和 TGF-β1 浓度的影响,以及对未经治疗的患者和健康对照组 T 细胞中磷酸化 STAT3 和 STAT5 蛋白水平的影响。使用液滴数字 PCR 评估了未经治疗的 RRMS 患者血液中、接受干扰素-β、醋酸格拉替雷、富马酸二甲酯或特氟隆胺治疗的患者血液中以及健康对照组血液中 STAT1、STAT3、STAT5A、STAT5B、SOCS1、SOCS3、FOXP3、IKZF2、RORC 和 ICOS 基因的表达情况。血清中 sgp130 和 TGF-β1 的浓度通过 ELISA 进行评估。流式细胞术评估了 T 细胞中磷酸化 STAT3 和 STAT5 蛋白水平。未经治疗的患者 STAT3 基因表达明显高于健康对照组,但 T 细胞中磷酸化 STAT3 的水平明显低于健康对照组。接受干扰素-β或富马酸二甲酯治疗的患者的STAT3基因表达量明显较低。与未接受治疗的患者相比,接受特立氟胺治疗的患者 STAT1 基因表达较高。接受富马酸二甲酯治疗的患者的 RORC 基因表达也明显低于未接受治疗的患者。这项研究显示了用于复发性多发性硬化症一线治疗的药物对 STAT 和 T 细胞相关基因表达的影响。
Expression of STAT- and T-cell-related genes in women with first-line treatment of relapsing-remitting multiple sclerosis.
Relapsing-remitting multiple sclerosis is associated with changes in Jak/STAT pathways in immune cells, but the influence of disease-modifying drugs on these pathways is poorly understood. The aim of this study was to evaluate the impact of first-line disease-modifying drugs used in treatment of RRMS on expression of the STAT pathway and T-cell-related genes in the blood and on serum concentrations of sgp130 and TGF-β1 in women, as well as on the level of phosphorylated STAT3 and STAT5 proteins in T cells of untreated patients and heathy controls. Expression of STAT1, STAT3, STAT5A, STAT5B, SOCS1, SOCS3, FOXP3, IKZF2, RORC and ICOS genes in the blood of untreated RRMS patients, in the blood of patients treated with interferon-β, glatiramer acetate, dimethyl fumarate or teriflunomide and in the blood of healthy controls was evaluated using droplet digital PCR. Serum concentrations of sgp130 and TGF-β1 were evaluated by ELISA. Phosphorylated STAT3 and STAT5 protein levels in T cells were evaluated by flow cytometry. STAT3 gene expression was significantly higher in untreated patients than in healthy control, but the level of phosphorylated STAT3 in T cells was significantly lower. Patients treated with interferon-β or dimethyl fumarate had significantly lower STAT3 gene expression. Patients treated with teriflunomide had higher STAT1 gene expression, than untreated patients. Patients treated with dimethyl fumarate also had significantly lower RORC gene expression than untreated patients. The study shows the impact of drugs used in first-line treatment of relapsing-remitting multiple sclerosis on expression of STAT and T-cell-related genes.
期刊介绍:
This peer-reviewed international journal publishes original articles and reviews on all aspects of basic, translational and clinical immunology. The journal aims to provide high quality service to authors, and high quality articles for readers.
The journal accepts for publication material from investigators all over the world, which makes a significant contribution to basic, translational and clinical immunology.