Differential regulation and correlation between galectin-9 and anti-CCP antibody (ACPA) in rheumatoid arthritis patients
Differential regulation and correlation between galectin-9 and anti-CCP antibody (ACPA) in rheumatoid arthritis patients
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DOI：
10.1186/s13075-020-02158-3
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发表时间：
2020-04-15
影响因子：
4.9
通讯作者：
Migita, Kiyoshi
中科院分区：
文献类型：
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作者：
Fujita, Yuya;Asano, Tomoyuki;Migita, Kiyoshi
研究背景半乳糖凝集素-9（Galectin-9，Gal-9）参与免疫应答或炎症的调节过程。本研究的目的是描述类风湿关节炎（RA）患者的循环Gal-9及其与RA疾病活动和表型的关系。方法选择116例RA患者和31例健康对照者作为研究对象。采用28关节疾病活动度评分系统（DAS 28-ESR）测定RA患者的疾病活动度。采用酶联免疫吸附试验（ELISA）测定血清中Gal-9的水平。结果RA患者血清Gal-9水平显著高于对照组（中位数7577 pg/ml [四分位距（IQR）5570- 10，201] vs 4738 pg/ml [IQR 4267-5630]，p = 0.001）。RA伴或不伴RA-ILD患者血清Gal-9水平差异有统计学意义（9606 pg/ml [IQR 8522- 12，167] vs 7078 pg/ml [IQR 5225-9447]，p < 0.001）或有和无晚期关节损伤的患者（II-IV期，9606 pg/ml [IQR 8522- 12，167]对比7078 pg/ml [IQR 5225-9447]，p < 0.001）。虽然血清Gal-9水平与ACPA滴度相关（r = 0.275，p = 0.002），但ACPA滴度水平赋予血清Gal-9与炎症介质或RA疾病活动性之间的不同关系。虽然Gal-9与ACPA滴度相关（r = 0.508，p = 0.002），但在ACPA滴度高（> 200 U/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DAS 28-ESR之间无相关性。相反，Gal-9与MMP-3（r = 0.300，p = 0.007）或DAS 28-ESR（r = 0.331，p = 0.004）相关，但与ACPA滴度低（< 200 U/ml）的RA患者的ACPA滴度无关。结论RA患者血清Gal-9水平升高，且在ACPA阴性的RA患者中，Gal-9水平与RA疾病活动性相关。ACPA滴度水平可能影响不同临床表型RA患者循环Gal-9的值。这些数据表明，在ACPA滴度的状态下，Gal-9具有促炎或关节病生物标志物的性质。
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.