AB0120 ENZYMATIC PATTERN OF CIRCULATING XANTHINE OXIDOREDUCTASE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Abstract

BackgroundGeneralized autoimmune inflammation underlies the pathogenesis of systemic lupus erythematosus (SLE). At the same time metabolic disorders at the cellular and subcellular levels are involved in the development of the disease. The literature contains data confirming the role of reactive oxygen species and oxidative stress in SLE multi-organ involvement [1,2].Objectivesto evaluate the changes in XOR activities in plasma, lysed white blood cells (WBC), and lysed red blood cells (RBC) of SLE patients.MethodsDiagnosis of SLE was verified using the SLICC criteria (2012). Activities of XOR interconvertible forms, xanthine oxidase (XO) and xanthine dehydrogenase (XDG), were measured in plasma, lysed WBC and lysed RBC by the spectrophotometric method [3]. The enzymatic activities were expressed as nmol/min/ml and normalized to 1×107 cells/ml in lysed WBC, and to 1×109 cells/ml in lysed RBC. The results were expressed as Me (Q25; Q75). Statistical comparison tests were selected in according to the common guidelines. Differences were considered significant when p<0.05. Reference ranges were calculated as 95th percentile interval.Results56 adult SLE patients (mean age 35 (31; 42) years; mean disease duration was 8 (5; 11) years)) and 35 healthy individuals were enrolled in the study. Reference intervals of plasma XO and XDG activities were 2.29 – 4.31 and 4.52 – 5.97 nmol/min/ml, respectively. Reference intervals of XO and XDG activities in lysed WBC were 14.11 – 31.33 and 18.62 – 39.65 nmol/min/ml, respectively. Reference intervals of XO and XDG activities in lysed RBC were 20.62 – 25.46 and 41.89 – 55.04 nmol/min/ml, respectively. Enzymatic activities of SLE patients were significantly different from healthy controls. Increased XO activity and decreased XDG activity were observed in plasma of SLE patients (p<0.001 for both enzymes). The activities of both XOR forms were decreased in lysed WBC (p<0.001 for both enzymes). Lysed RBC were characterized by a decrease in XDH activity (p<0.001).ConclusionSignificant changes in the balance of XO and XDG activities were revealed in plasma, lysed WBC and RBC of SLE patients., These enzymes can also exhibit NADH oxidase and nitrate reductase activities under conditions of low pH and hypoxia. Such conditions are formed in SLE due to the development of pronounced inflammation and microthrombosis in various tissues. Reactive forms of oxygen and nitrogen, which production is increased as a result of XOR activity, have a damaging effect on cellular structures, initiate the processes of lipid peroxidation, participate in the stimulation of NF-kB, and contribute to the formation of neutrophil extracellular traps. It can be assumed that the imbalance of XOR enzymatic activities in WBC indicates the previous stages of purine metabolism disturbances, which leads to a change in functional state and death of these blood cells. Free radicals generated by the XOR may have a damaging effect on RBC.