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半乳糖凝集素-9 作为系统性红斑狼疮疾病活动的生物标志物。

Galectin-9 as a biomarker for disease activity in systemic lupus erythematosus.

机构信息

Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Clinical Research Center, Nagasaki Medical Center, Nagasaki, Japan.

出版信息

PLoS One. 2020 Jan 27;15(1):e0227069. doi: 10.1371/journal.pone.0227069. eCollection 2020.

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by elevated interferon (IFN) signature genes. Galectin-9 (Gal-9) is a β-galactoside-binding lectin that is reportedly useful as a biomarker for IFN gene signatures. In a cross-sectional study of Japanese patients with recent-onset SLE, we aimed to determine whether raised serum Gal-9 levels were associated with the disease activity or organ damage seen in SLE patients.

METHODS

The current study included 58 Japanese patients with SLE and 31 age-matched healthy individuals. Disease activity and organ damage were assessed using SLE Disease Activity 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC) damage index. Serum and cerebrospinal fluid (CSF) Gal-9 concentrations were quantified using ELISA. Correlation analyses between Gal-9 and clinical parameters including disease activity were performed.

RESULTS

Serum levels of Gal-9 were significantly increased in patients with SLE compared with the control group (16.6 ng/ml, [interquartile range (IQR); 3.6-59.7] versus 4.74 ng/ml, [IQR; 3.0-9.5], p<0.0001). Gal-9 was significantly correlated with disease activity measures in the SLEDAI-2K. Serum Gal-9 levels were significantly greater in patients with SLE-related organ involvement (23.1 ng/ml, [IQR; 5.1-59.7] versus 12.5ng/ml, [IQR; 3.6-39.0], p = 0.013). Whereas there was no difference in serum levels of CXCL10 or M2BPGi between patients with and without SLE-related organ involvement. Serum levels of Gal-9 were significantly higher in SLE patients with active renal involvement determined by BILAG renal score (A-B) compared to those without active renal involvement (C-E). Whereas there was no significant difference in serum levels of Gal-9 between SLE patients with or without active other organ involvements (neurological or hematological) determined by BILAG score. SLE patients with detectable circulating IFN-α had raised serum Gal-9 levels. Levels of Gal-9 were significantly higher in the CSF from patients with recent-onset neuropsychiatric SLE (NPSLE) than in those from non-SLE controls (3.5 ng/ml, [IQR; 1.0-27.2] versus 1.2 ng/ml, [IQR; 0.9-2.1], p = 0.009).

CONCLUSIONS

Gal-9 could be a serologic marker of disease activity and organ involvement in SLE patients. Future studies evaluating the role of Gal-9 in the SLE phenotype may provide insights into SLE pathogenesis.

摘要

背景

系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特征为干扰素(IFN)特征基因升高。半乳糖凝集素-9(Gal-9)是一种 β-半乳糖苷结合凝集素,据报道可作为 IFN 基因特征的生物标志物。在一项对日本新诊断 SLE 患者的横断面研究中,我们旨在确定血清 Gal-9 水平升高是否与 SLE 患者的疾病活动或器官损伤有关。

方法

本研究纳入了 58 例日本 SLE 患者和 31 名年龄匹配的健康对照者。使用 SLE 疾病活动度 2000 评分(SLEDAI-2K)和系统性红斑狼疮国际合作临床(SLICC)损害指数评估疾病活动度和器官损害。采用 ELISA 法检测血清和脑脊液(CSF)Gal-9 浓度。对 Gal-9 与疾病活动等临床参数之间的相关性进行分析。

结果

SLE 患者的血清 Gal-9 水平明显高于对照组(16.6ng/ml,[四分位距(IQR);3.6-59.7] 与 4.74ng/ml,[IQR;3.0-9.5],p<0.0001)。Gal-9 与 SLEDAI-2K 中的疾病活动度指标显著相关。SLE 相关器官受累患者的血清 Gal-9 水平显著升高(23.1ng/ml,[IQR;5.1-59.7] 与 12.5ng/ml,[IQR;3.6-39.0],p=0.013)。而 SLE 相关器官受累患者与无 SLE 相关器官受累患者的血清 CXCL10 或 M2BPGi 水平无差异。BILAG 肾脏评分(A-B)判定为有活动肾脏受累的 SLE 患者的血清 Gal-9 水平明显高于无活动肾脏受累的患者(C-E)。而 BILAG 评分判定为有活动其他器官受累(神经或血液)的 SLE 患者的血清 Gal-9 水平无差异。可检测到循环 IFN-α的 SLE 患者的血清 Gal-9 水平升高。初发神经精神性 SLE(NPSLE)患者的脑脊液中 Gal-9 水平明显高于非 SLE 对照组(3.5ng/ml,[IQR;1.0-27.2] 与 1.2ng/ml,[IQR;0.9-2.1],p=0.009)。

结论

Gal-9 可能是 SLE 患者疾病活动度和器官受累的血清标志物。评估 Gal-9 在 SLE 表型中的作用的未来研究可能会深入了解 SLE 的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b515/6984724/8a200eef8349/pone.0227069.g001.jpg

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