Differential regulation and correlation between galectin-9 and anti-CCP antibody (ACPA) in rheumatoid arthritis patients

Abstract

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 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 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.

Aberrantly Expressed Galectin-9 is Involved in the Immunopathogenesis of anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease

“…Elevated serum Gal-9 levels have been detected in various autoimmune disease [31][32][33]. Consist with the previous studies in patients with juvenile DM [25,26], our study demonstrated that adult patients with DM exhibited increased serum Gal-9 levels compared to those in HCs.…”

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

“…We previously demonstrated that circulating Gal-9 is elevated and partly correlated with the titers of autoantibodies in patients with autoimmune diseases [28,29]. However, the more elevated levels of serum galectin-9 were demonstrated and positively correlated with disease activity in an autoinflammatory disease, ASD.…”

Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus

“…In support of our findings regarding TNF, the in vitro model using IC stimulation of PBMCs resulted in profound TNF production and such IC driven TNF production has been demonstrated previously ( 39 ). Of further interest in this context, two recent studies have reported galectin-9 as a valuable biomarker of disease activity in another TNF-driven disease – namely rheumatoid arthritis (RA) ( 40 , 41 ).…”