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血清可溶性 TRAIL:肌炎患者疾病活动的潜在生物标志物。

Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients.

机构信息

Department of Rheumatology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, China.

Department of Medical and Health Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

Clin Rheumatol. 2019 May;38(5):1425-1431. doi: 10.1007/s10067-018-04418-9. Epub 2019 Jan 15.

Abstract

OBJECTIVES

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features.

METHOD

11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry.

RESULTS

TRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls.

CONCLUSIONS

The serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.

摘要

目的

肿瘤坏死因子相关凋亡诱导配体(TRAIL)是 TNF 超家族的一员,参与免疫反应的调节和自身免疫性疾病的发病机制,包括多发性肌炎(PM)和皮肌炎(DM)。在这项研究中,我们检测了 PM 和 DM 患者血清可溶性 TRAIL(sTRAIL)的水平和来源,并分析了其与疾病活动度和临床特征的关系。

方法

本研究纳入 11 例 PM 患者、33 例 DM 患者和 20 例健康对照者。入院时记录临床特征,采用肌炎疾病活动评估视觉模拟量表(MYOACT)评估疾病活动度。免疫组织化学检测肌肉组织中 TRAIL 的表达。采用酶联免疫吸附试验检测血清 sTRAIL 水平。采用流式细胞术分析循环 T 细胞表面膜 TRAIL(mTRAIL)及其受体 DR4 和 DR5 的表达。

结果

TRAIL 在患者肌肉组织浸润性炎症细胞中表达。患者血清 sTRAIL 水平明显升高,与疾病活动度呈正相关。治疗后患者血清 sTRAIL 水平降低,且吞咽困难患者 sTRAIL 水平更高,抗 Jo-1 抗体阳性患者 sTRAIL 水平更低。与健康对照组相比,患者循环 T 细胞表面 mTRAIL 及其受体的频率明显升高。

结论

血清 sTRAIL 可作为评估 PM 和 DM 疾病活动度的生物标志物,靶向 T 细胞中 TRAIL 的产生可能是治疗 PM 和 DM 的一种潜在方法。

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