Galectin-9 expression correlates with therapeutic effect in rheumatoid arthritis

Jiao Sun,Yameng Sui,Yunqing Wang,Guosheng Li,Dong Li,Jianwei Liu,Lijun Song,Qiang Shu

doi:10.1038/s41598-021-85152-2

Abstract

Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and therapeutic response in RA patients. Active RA patients were enrolled and treated with tacrolimus (TAC) alone or in combination therapy for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and week 12. We measured Gal-9 expression in different T cell subsets and in plasma. The disease activity of RA patients decreased after treatment. At baseline, the Gal-9 expression percentage was higher in the group with severe disease than in mild or moderate groups. After treatment, the Gal-9 expression in CD3+, CD4+, CD8+ and CD4-CD8− cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3+, CD4+ and CD8+ T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets and lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients. Gal-9 can be regarded as a new biomarker for evaluating RA activity and therapeutic effect, including TAC.

Highlights

Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in Rheumatoid arthritis (RA)
Our previous studies showed that Gal-9 levels in peripheral blood mononuclear cells (PBMCs) and plasma are higher in RA patients than in healthy controls, and plasma Gal-9 level positively correlates with disease activity
In our prospective cohort study, we evaluated the features of Gal-9 as a biological marker for drug response, as well as its relationship with disease activity in active RA patients

Summary

Introduction

Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and therapeutic response in RA patients. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets and lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients. The activation of T cells and related cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α are involved in cellular immune responses during R A2,3. TAC works as conventional disease-modifying anti-rheumatic drug (cDMARD) to reduce the systemic inflammatory response in patients with refractory R A7. Our previous studies showed that Gal-9 levels in peripheral blood mononuclear cells (PBMCs) and plasma are higher in RA patients than in healthy controls, and plasma Gal-9 level positively correlates with disease activity

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