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.
Highlights
Systemic Sclerosis (SSc), called scleroderma, is an immunemediated rheumatic disease, characterized by microvascular damage and fibrosis
The presence of skin involvement, calcinosis, telangiectasias, arthritis, muscle weakness, Raynaud’s phenomenon, interstitial lung disease (ILD) [defined by Computed Tomography resolution of the chest according to the definitions of the American Thoracic Society/European Respiratory Society 2002 consensus], pulmonary hypertension (PHT), ischemic lesions in fingers and dysphagia was recorded
Compelling evidence suggesting the involvement of galectins in the control of immune and vascular programs, as well as in fibrotic processes support a role for these proteins in SSc
Summary
Systemic Sclerosis (SSc), called scleroderma, is an immunemediated rheumatic disease, characterized by microvascular damage and fibrosis. Given the involvement of Gal-1 and Gal-3 in angiogenesis, immunity and extracellular matrix remodeling, a role of these lectins in SSc development, characterized by vascular alterations, inflammation and fibrosis has been proposed In this line, previous studies evaluated possible differences in Gal-1 (Yanaba et al, 2016) and Gal-3 (Taniguchi et al, 2012; Koca et al, 2014; Gruszewska et al, 2020) serum levels between SSc patients and controls, and reported different paradoxical results. In line with this demand, and considering the previous inconclusive findings, we aimed at determining serum levels of Gal-1 and Gal-3 in patients with SSc and to evaluate possible associations with clinical manifestations of the disease and treatment options
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