AB0164 ACTIVITIES OF THE OXIDATIVE-RELATED ENZYMES IN SYSTEMIC SCLEROSIS

Abstract

Background:The oxidative-related enzymes are involved in the pathogenesis of various stages of systemic sclerosis (SSc). SSc is a chronic autoimmune disorder that is intimately associated with vascular damage and therefore with chronic perfusion/reperfusion and oxidative organ injury. Mesenchymal cell activation in SSc is now also considered to be mediated primarily through oxidative burst. Regulation of oxidative stress by specific enzymes including several purine metabolism enzymes is likely to play an important role in SSc progression.Objectives:to characterize interrelationships among circulating xanthine oxidase (XO), xanthine dehydrogenase (XDH), superoxide dismutase (SOD) activities and SSc activity.Methods:The study was performed according to bioethical standards. 51 patients with verified SSc and 30 healthy controls were included in the study. The diagnosis was verified according to ACR/EULAR 2013 criteria. We assessed SSc activity in compliance with the original activity scale that is commonly used in Russia [Guseva N.G., 1993] and by the 2001 European Scleroderma Study Group Activity Index. XO (EC 1.17.3.2), XDH (EC 1.17.1.4), and SOD (EC 1.15.1.1) plasma activities were measured using spectrophotometric techniques as previously described [Dubinina E.E., 1986; Karpova O.V., 2006]. Results are expressed as mean±SD. The Mann-Whitney U test and Spearman’s correlation coefficient were used for statistical analysis.Results:Mean age of patients was 42.8±1.3 years, mean SSc duration was 7.9±0.7 years. Mean enzymatic activities in normal controls were 3.43±0.56 nmol/ml min (for XO), 5.19±0.71 nmol/ml min (for XDH), and 5.40±1.03 units (for SOD). The respective enzymatic activities in SSc group were 3.91±0.62 nmol/ml min, 7.10±0.71 nmol/ml min, and 7.10±2.19 units. All these mean activities were significantly higher in SSc patients comparing to healthy individuals (p<0.001). XO and XDH activities positively correlated with SSc activity (r=0.499, p<0.001, and r=0.741, p<0.001, respectively). The opposite but weaker trend was observed for SOD activity and SSc disease activity (r=-0.190, p=0.188).Conclusion:SSc is characterized by an increase in the intensity of oxidative and antioxidant processes, more pronounced in high disease activity. A close relationship between function of prooxidant/antioxidant enzymes and some of the key SSc pathogenetic mechanisms, especially vascular disease and fibroblast activation, is widely considered. Overall increase of oxidative stress in patients with higher disease activity, as well as depletion of antioxidant capacity can be also linked with disturbance of purine metabolism through XO and XDH modulation. Pathogenetic influence of this imbalance can also be mediated through initial phase of neutrophil extracellular traps (NETs) formation, an eventual source of nucleoprotein containing autoepitopes.Disclosure of Interests:None declared