Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Clinical Research Center, Nagasaki Medical Center, Nagasaki, Japan.
PLoS One. 2020 Jan 27;15(1):e0227069. doi: 10.1371/journal.pone.0227069. eCollection 2020.
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.
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.
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).
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.
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。
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。
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)。
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。