Sundblad Victoria, Gomez Ramiro A, Stupirski Juan C, Hockl Pablo F, Pino Maria S, Laborde Hugo, Rabinovich Gabriel A
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad de Buenos Aires, Argentina.
División Reumatología, Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
Front Pharmacol. 2021 Apr 20;12:650605. doi: 10.3389/fphar.2021.650605. eCollection 2021.
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 = 17; lcSSc = 64; ssSSc = 2), and evaluated their association with clinical manifestations of the disease. Patients with dcSSc showed lower Gal-3 levels, compared to lcSSc ( = 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 ( = 0.015), and higher concentrations Gal-3 were associated with telangiectasias ( = 0.021), diarrhea ( = 0.039) and constipation ( = 0.038). Moreover, lower Gal-3 levels were associated with the presence of tendinous retractions ( = 0.005). Patients receiving calcium blockers ( = 0.048), methotrexate ( = 0.046) or any immunosuppressive treatment ( = 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 ( 0.25; = 0.022 and 0.26; = 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.
系统性硬化症(SSc)是一种以纤维化、微血管损伤和免疫失调为特征的风湿性疾病。根据皮肤受累程度可分为两个主要亚型,即局限性皮肤系统性硬化症(lcSSc)和弥漫性皮肤系统性硬化症(dcSSc)。越来越多的证据表明半乳糖凝集素在免疫和血管程序、细胞外基质重塑及纤维化中发挥作用,提示它们可能参与了系统性硬化症的发病过程。在此,我们测定了83例系统性硬化症患者(其中dcSSc = 17例;lcSSc = 64例;ssSSc = 2例)血清中半乳糖凝集素(Gal)-1和Gal-3的水平,并评估了它们与该疾病临床表现的相关性。与lcSSc患者相比,dcSSc患者的Gal-3水平较低(P = 0.003),而两组间Gal-1水平未检测到显著差异。值得注意的是,较高浓度的Gal-1与毛细血管扩张的存在相关(P = 0.015),较高浓度的Gal-3与毛细血管扩张(P = 0.021)、腹泻(P = 0.039)和便秘(P = 0.038)相关。此外,较低的Gal-3水平与肌腱挛缩的存在相关(P = 0.005)。与未接受此类治疗的患者相比,接受钙通道阻滞剂治疗(P = 0.048)、甲氨蝶呤治疗(P = 0.046)或任何免疫抑制治疗的患者(P = 0.044)的Gal-3浓度较低。在多元线性回归模型中,毛细血管扩张的存在和系统性硬化症的类型与Gal-3仍保持统计学关联(分别为β = 0.25;P = 0.022和β = 0.26;P = 0.017)。总之,血清Gal-3水平与系统性硬化症的临床表现相关。其中,毛细血管扩张的存在可通过这种凝集素在血管生成程序中的核心作用来解释。