THU0405 The association between baseline serum resistin levels and the development of new digital ulcers in patients affected by systemic sclerosis

Background Resistin is a soluble factor produced by adipose tissue, implicated in the regulation of inflammatory processes and in microvascular damage.1 When incubated with resistin, endothelial cells respond by a greater production of endothelin-1, a potent endothelium-derived vasoactive factor that engenders endothelial dysfunction (ED) in many cardiovascular and autoimmune diseases, such as Systemic Sclerosis (SSc).2 SSc is a complex connective tissue disease, whose pathogenesis results from the variable interaction of three main processes: microvascular damage, autoimmunity-mediated inflammation and fibroblast activation.3 ED is at the base of the development of painful ischaemic events due to chronic hypoxia, namely digital ulcers (DUs),4 considered a prognostic marker of disease severity.5 Objectives To evaluate the association between baseline serum resistin levels and the development of new DUs in a cohort of patients with SSc. Methods We conducted a one-year prospective cohort study. Patients with SSc and healthy controls (HC) were consecutively enrolled. Baseline serum resistin was assessed by commercial ELISA kit. The development of new DUs was prospectively evaluated during the follow-up after the cross-sectional point in which the resistin levels were measured. Results We enrolled 70 SSc patients and 26 HC matched by gender and vital parameters. Mean basal resistin levels were increased in SSc patients compared to HC (6.58±5.48 vs 2.56±0.95, p=0.0004). In SSc group, resistin was higher among patients with active DUs (p=0.0007), infected DUs (p=0.0009) and active pattern at nailfold videocapillaroscopy (p=0.01). During one-year follow-up, 27 (38%) SSc patients presented new skin ulcers. Baseline resistin was increased in patients who developed new DUs (8.4±6.4 vs 5.4±4.5, p=0.026). In multiple logistic regression, the development of new DUs was associated to basal serum resistin concentration (OR 2.1, 95% CI 1.1–3.9), to the presence of active DUs at baseline (OR 3.4, 95% CI 1.0–11.9), and to basal Disease Activity Score (DAI) according to European Scleroderma Study Group6 (OR 1.3, 95% CI 1.0–1.6). In proportional Cox regression, the time to new DUs was associated to basal resistin concentration (HR 1.7, 95% CI 1.1–2.8) and DAI (HR 1.2, 95% CI 1.0–1.4). Conclusions Serum resistin seems to be associated to the presence and to the development of DUs, suggesting a possible involvement in micro-vascular dysfunction in patients affected by SSc. References [1] Pang SS, Le YY. Role of resistin in inflammation and inflammation-related diseases. Cell Mol Immunol2006;3:29–34. [2] Verma S, Li SH, et al. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation2003;108:736–40. [3] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med2009;360:1989–2003. [4] Hughes M, Herrick AL. Digital ulcers in systemic sclerosis. Rheumatology (Oxford)2017;56:14–25. [5] Mihai C, Landewe R, et al. Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis2016;75:681–6. [6] Valentini G, Della Rossa A, et al. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis2001;60:592–8. Disclosure of Interest None declared