Differential Regulation and Correlation between Galectin-9 and anti-CCP antibody (ACPA) in Rheumatoid Arthritis Patients

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 116 RA patients and age-matched healthy controls (n=31) were included in this study. Disease activity of RA patients were 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); 5570–10201] 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: 8522–12167] 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: 8522–12167] 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 (>200u/ml). Conversely, Gal-9 was correlated with MMP-3 (r=0.300, p=0.007) or DAS28-ESR (r=0.331, p=0.004) not with ACPA titer in RA patients with low titers of ACPA titers (<200U/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 phenotype. These data suggest that Gal-9 possessed the properties of proinflammatory or arthropathic biomarker under the status of ACPA titers.