类风湿关节炎患者中半乳糖凝集素-9 与抗环瓜氨酸肽抗体（ACPA）的差异调节及其相关性。
Differential regulation and correlation between galectin-9 and anti-CCP antibody (ACPA) in rheumatoid arthritis patients.
机构信息
Department of Rheumatology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Department of Immunology and Rheumatology, Unit of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences,, Nagasaki University, Sakamoto1-7-1, Nagasaki, 852-8501, Japan.
出版信息
Arthritis Res Ther. 2020 Apr 15;22(1):80. doi: 10.1186/s13075-020-02158-3.
BACKGROUND
Galectin-9 (Gal-9) is involved in the regulatory process of immune responses or inflammation. The aim of the present study is to characterize circulating Gal-9 in patients with rheumatoid arthritis (RA) and its relationship with RA disease activity and phenotype.
METHODS
A total of 116 RA patients and 31 age-matched healthy controls were included in this study. Disease activity of RA patients was determined by Disease Activity Score of 28 joint scoring system (DAS28-ESR). Levels of Gal-9 in serum were determined by enzyme-linked immunosorbent assay (ELISA).
RESULTS
Serum levels of Gal-9 were significantly higher in patients with RA compared to those in controls (median 7577 pg/ml [interquartile range (IQR) 5570-10,201] versus 4738 pg/ml [IQR 4267-5630], p = 0.001). There were significant differences in serum Gal-9 between RA patients with and without RA-ILD (9606 pg/ml [IQR 8522-12,167] versus 7078 pg/ml [IQR 5225-9447], p < 0.001) or those with and without advanced joint damage (stage II-IV, 9606 pg/ml [IQR 8522-12,167] versus 7078 pg/ml [IQR 5225-9447], p < 0.001). Although serum levels of Gal-9 correlated with the titers of ACPA (r = 0.275, p = 0.002), levels of ACPA titers conferred the different relationship, between serum Gal-9 and inflammatory mediators or RA disease activity. Although Gal-9 was correlated with ACPA titers (r = 0.508, p = 0.002), there was no correlation between Gal-9 levels and erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3 (MMP-3), or DAS28-ESR in RA patients with high titers of ACPA (> 200 U/ml). Conversely, Gal-9 was correlated with MMP-3 (r = 0.300, p = 0.007) or DAS28-ESR (r = 0.331, p = 0.004) but not with ACPA titer in RA patients with low titers of ACPA titers (< 200 U/ml).
CONCLUSIONS
Serum levels of Gal-9 were increased in RA patients and associated with RA disease activity in RA patients without high titers of ACPA. The levels of ACPA titers may influence the values of circulating Gal-9 in RA patients with various clinical phenotypes. These data suggest that Gal-9 possessed the properties of pro-inflammatory or arthropathic biomarker under the status of ACPA titers.
背景
半乳糖凝集素-9（Gal-9）参与免疫反应或炎症的调节过程。本研究旨在描述类风湿关节炎（RA）患者循环 Gal-9 的特征及其与 RA 疾病活动度和表型的关系。
方法
本研究纳入了 116 例 RA 患者和 31 名年龄匹配的健康对照者。采用 28 关节疾病活动评分（DAS28-ESR）评估 RA 患者的疾病活动度。采用酶联免疫吸附试验（ELISA）检测血清 Gal-9 水平。
结果
与对照组相比，RA 患者的血清 Gal-9 水平显著升高（中位数 7577pg/ml [四分位距（IQR）5570-10201] 比 4738pg/ml [IQR 4267-5630]，p=0.001）。血清 Gal-9 在有或无 RA-ILD（9606pg/ml [IQR 8522-12167] 比 7078pg/ml [IQR 5225-9447]，p<0.001）或有或无晚期关节损伤（Ⅱ-Ⅳ期）的 RA 患者之间存在显著差异（9606pg/ml [IQR 8522-12167] 比 7078pg/ml [IQR 5225-9447]，p<0.001）。尽管血清 Gal-9 与 ACPA 滴度相关（r=0.275，p=0.002），但 ACPA 滴度之间的关系不同，血清 Gal-9 与炎症介质或 RA 疾病活动度之间的关系不同。尽管 Gal-9 与 ACPA 滴度相关（r=0.508，p=0.002），但在 ACPA 滴度高（>200U/ml）的 RA 患者中，Gal-9 水平与红细胞沉降率（ESR）、基质金属蛋白酶-3（MMP-3）或 DAS28-ESR 之间无相关性。相反，在 ACPA 滴度低（<200U/ml）的 RA 患者中，Gal-9 与 MMP-3（r=0.300，p=0.007）或 DAS28-ESR（r=0.331，p=0.004）相关，但与 ACPA 滴度无关。
结论
RA 患者血清 Gal-9 水平升高，与 ACPA 滴度不高的 RA 患者的疾病活动度相关。ACPA 滴度可能影响 RA 患者不同临床表型中循环 Gal-9 的水平。这些数据表明，在 ACPA 滴度状态下，Gal-9 具有促炎或关节病生物标志物的特性。
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