Clinical Relevance of Galectin-1 and Galectin-3 in Rheumatoid Arthritis Patients: Differential Regulation and Correlation With Disease Activity

Abstract

Galectins, a family of animal lectins, play central roles in immune system regulation, shaping both innate and adaptive responses in physiological and pathological processes. These include rheumatoid arthritis (RA), a chronic multifactorial autoimmune disease characterized by inflammatory responses that affects both articular and extra-articular tissues. Galectins have been reported to play central roles in RA and its experimental animal models. In this perspective article we present new data highlighting the regulated expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) in sera from RA patients under disease-modifying anti-rheumatic drugs (DMARDs) and/or corticoid treatment in the context of a more comprehensive discussion that summarizes the roles of galectins in joint inflammation. We found that Gal-1 levels markedly increase in sera from RA patients and positively correlate with erythrocyte sedimentation rate (ERS) and disease activity score 28 (DAS-28) parameters. On the other hand, Gal-3 is downregulated in RA patients, but positively correlates with health assessment questionnaire parameter (HAQ). Finally, by generating receiver-operator characteristic (ROC) curves, we found that Gal-1 and Gal-3 serum levels constitute good parameters to discriminate patients with RA from healthy individuals. Our findings uncover a differential regulation of Gal-1 and Gal-3 which might contribute to the anti-inflammatory effects elicited by DMARDs and corticoid treatment in RA patients.

Validation of galectin-1 as potential diagnostic biomarker of early rheumatoid arthritis

“…A baseline Gal1 serum level > 19 ng/ml showed a good performance to discriminate HD from either RA or UA patients. The difference between the cut-off point proposed in the study by Mendez-Huergo et al and our study could be due to the use of different ELISA kits to measure Gal1 in serum 18 . In our case, we used a commercial kit, which showed very low variability between tests.…”

“…In order to validate the report by Mendez-Huergo et al describing that patients with RA show higher Gal1 serum levels than healthy donors 18 , we measured Gal1 levels in serum from 62 patients included in the PEARL study. Patients were clustered in two different populations (Pop1 and Pop2) and 24 healthy donors (HD) were also studied.…”

“…In addition, treatment with recombinant Gal1 improves clinical manifestations of established collagen-induced arthritis (CIA) 15 . A recent cross-sectional study described that RA patients show higher Gal1 serum levels 18 . However, other authors have described similar Gal1 serum levels in RA patients and healthy controls 19 .…”

Assessment of saliva and gingival crevicular fluid soluble urokinase plasminogen activator receptor (suPAR), galectin‐1, and TNF‐α levels in periodontal health and disease

“…21 It has been shown that galectin-1 levels markedly increased in serum of RA patients and positively correlated with disease activity score 28 (DAS-28) parameters. 48 Reesink et al 49 reported that galectin-1 levels increased with increasing osteoarthri- to compensate excessive inflammation. 50,51 No significant difference was found between study groups in terms of saliva concentration of galectin-1.…”

Regulators of TNFα Mediated Insulin Resistance Elucidated by Quantitative Proteomics

“…Along similar lines, galectin-1 (Lgals1) attenuates acute inflammation in rats, and have also been shown to inhibit 3T3-L1 adipocyte differentiation (Rabinovich et al, 2000;Mendez-Huergo et al, 2019). The downregulation of Lgals1 is possibly an important factor that contributes to the dysregulation of adipocyte and macrophage inflammatory responses upon chronic TNFα exposure.…”