Angiopoietins-1 and-2 are differentially expressed in the sera of patients with systemic sclerosis: high angiopoietin-2 levels are associated with greater severity and higher activity of the disease

Methods. Serum levels of Ang-1 and -2 were determined by ELISA in 47 SSc patients and 27 healthy controls matched for age and sex. Results. In SSc patients, Ang-1 was significantly lower [mean (s.d.): 21 666.09 (11 516.06) pg/ml], while Ang-2 was significantly increased [2739.60 (1009.25) pg/ml] when compared with the control group [Ang-1: 28607.13 (10 506.93) pg/ml; Ang-2: 1706.28 (556.28) pg/ml, P < 0.01, for both comparisons]. No correlation was observed between Ang-1 and -2 levels. Serum concentrations of Ang-2 correlated with the modified Rodnan skin score (P < 0.01, r = 0.422), the European Scleroderma Study Group (EScSG) disease activity index score (P < 0.001, r = 0.403), ESR (P < 0.05, r = 0.366) and CRP concentration (P < 0.05, r = 0.292), and showed inverse correlation with diffusing capacity for carbon monoxide (DLCO) (P < 0.01, r = -0.281). Ang-2 was significantly increased in SSc patients with more advanced capillary damage, as indicated by the presence of late capillaroscopic pattern, than in those with less severe microangiopathy (active pattern), and in SSc patients with intermediate/late stage of disease than in SSc subjects with early disease. In multivariate regression analysis, Ang-2 was independently associated with the EScSG activity index [beta-coefficient (beta = 0.305, P = 0.038], ESR (beta = 0.390, P = 0.006) and, inversely, with the presence of digital ulcers (beta = -0.426, P = 0.003). Conclusions. Differential expression of Ang-1/Ang-2 might contribute to the pathogenesis of SSc. Ang-2 might be a new biomarker of disease activity in SSc.