INVOLVEMENT OF OXIDATIVE STRESS AND VITAMINS D,C AND A IN SYSTEMIC SCLEROSIS: IN RELATION TO CLINICAL DISEASE ACTIVITY PARAMETERS

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by fibrosis of the skin and internal organs, vasculopathies, Raynaud's phenomenon (RP) with digital vasculopathies, and leg ulcers. Early diagnosis and personalized treatment are limited by few studies on SSc’s pathogenetic mechanisms. In the last years the role of oxidative stress (OxS) and deficiency of some micronutrients, including vitamins, have been highlighted.We evaluated the role of OxS and the oxidative burst capacities of polymorphonuclear leukocytes (PMN) by examining derivative-Reactive Oxygen Metabolites (d-ROMs), Thiobarbituric Acid Reactive Species (TBARS) and PhagoBurst in 42 patients with SSc, 14 with RP and 20 healthy controls (HC). In addition the blood level of vitamins A, C, D, were measured. Correlation analysis was performed between OxS markers and clinical disease activity parameters (DA), evaluated by European Scleroderma Study Group (ESSG) index and the Number of microhaemorrage (NEMO) score.The markers of oxidative stress in blood of SSc patients were aberrant indicating an imbalance between oxidants and antioxidants. Both SSC and RP patients had higher OxS level compared with HC [d-ROM test: 380 (SSC), 330.5 (RP) and 280 UCARR (HC), <0.0001; TBARS: 0.1 (SSC),0.12 (RP) and 0.07 nmolMDA/mg protein (HC), p=0.009]. The differential analysis based on DA parameters demonstrated that d-ROMs values were higher in patients with: a) NEMO score ≥8 (451 vs 354; p=0.01) and the two parameters were positively correlated (r =0.42, p=0.005); b) scleredema (451 vs 348; p=0.04); c) digital ulcers (DU) (374 vs 427, p<0.0001). Lower levels of TBARS was measured in SSc with DU (0.05 vs 0.11; p=0.02). Data of the oxidative burst activity experiments upon stimulation with unlabeled opsonized bacteria (E.coli) demonstrated a reduced activity of granulocytes, producing fewer ROMs in SSc subjects. Reduced level of vitamin D, C and A was measured in SSc and their values were correlated with OxS parameters. Our results evidence that OxS correlates with the DA parameters which define both early skin and vascular signs, supporting the importance of its involvement in these stages, and also suggest a novel approach for SSc treatment considering micronutrients' supplementations.