Circulating Galectin-1 and Galectin-3 in Sera From Patients With Systemic Sclerosis: Associations With Clinical Features and Treatment

Abstract

Systemic Sclerosis (SSc) is a rheumatic disease characterized by fibrosis, microvascular damage and immune dysregulation. Two major subsets, limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc) can be defined, according to the extent of skin involvement. Increasing evidence indicates a role for galectins in immune and vascular programs, extracellular matrix remodeling and fibrosis, suggesting their possible involvement in SSc. Here, we determined serum levels of galectin (Gal)-1 and Gal-3 in 83 SSc patients (dcSSc n = 17; lcSSc n = 64; ssSSc n = 2), and evaluated their association with clinical manifestations of the disease. Patients with dcSSc showed lower Gal-3 levels, compared to lcSSc (p = 0.003), whereas no considerable difference in Gal-1 levels was detected between groups. Remarkably, higher concentrations of Gal-1 were associated with the presence of telangiectasias (p = 0.015), and higher concentrations Gal-3 were associated with telangiectasias (p = 0.021), diarrhea (p = 0.039) and constipation (p = 0.038). Moreover, lower Gal-3 levels were associated with the presence of tendinous retractions (p = 0.005). Patients receiving calcium blockers (p = 0.048), methotrexate (p = 0.046) or any immunosuppressive treatment (p = 0.044) presented lower concentrations of Gal-3 compared to those not receiving such treatments. The presence of telangiectasia and the type of SSc maintained their statistical association with Gal-3 (β 0.25; p = 0.022 and β 0.26; p = 0.017, respectively) in multiple linear regression models. In conclusion, serum levels of Gal-3 are associated with clinical manifestations of SSc. Among them, the presence of telangiectasias could be explained by the central role of this lectin in the vascularization programs.

Myocardial Involvement Detected Using Cardiac Magnetic Resonance Imaging in Patients with Systemic Sclerosis: A Prospective Observational Study

“…We observed worsening of skin thickness and a decrease in pulmonary diffusing capacity over time in our patients. Contrary to previous studies [11,21,22], only GDF-15 correlated with these changes in our study. GDF-15 expression is induced during fibrosis development, and serum levels correlated strongly with clinical symptoms of lung fibrosis, which was the case in a previous study [25] as well as in our baseline study.…”

“…This biomarker is a multifunctional protein implicated in various biological processes, including fibrosis, angiogenesis, cell differentiation and apoptosis, and immune activation, all of which are associated with the development of systemic sclerosis [20]. Galectin-3 was significantly correlated with the extent, variety, symptoms, and signs of SSc [21], particularly the extent of skin fibrosis [22,23]. Its potential role as a biomarker of sub-clinic myocardial fibrosis (assessed using CMR) was first demonstrated in our baseline study [14].…”

Novel biomarkers in systemic sclerosis

“…Galectins are a subfamily of proteins involved in regulating numerous biological processes, including inflammation and blood vessel remodeling, both of which occur in scleroderma (also known as systemic sclerosis, SSc). Four galectins -galectin-1, galectin-3, galectin-7, and galectin-9 − have been investigated in scleroderma [22,23,24].…”

Galectin-3 as a Novel Multifaceted and Not Only Cardiovascular Biomarker in Patients with Psoriasis with Regard to Systemic Treatment—Preliminary Data

“…Given the undeniable fact that gal-3 is a marker of inter alia inflammation, oxidative stress, atherogenesis, angiogenesis, along with our significantly higher level in psoriatics, we can speculate that gal-3 levels might be a multidirectional inductor or stimulator of the mentioned processes involved in the pathogenesis of psoriasis. Significant elevation of serum gal-3 level was also noted in diseases related with skin other than psoriasis, such as Behcet’s disease, limited cutaneous systemic sclerosis, or lupus erythematosus [ 32 , 33 , 34 ].…”