Background:Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anticitrulline autoantibodies. Recent evidences suggest that impairment of neutrophil extracellular traps (NETs) could exert substantial influence on RA pathogenesis. The production of NETs depends heavily on the ROS generation. One of its mechanisms is xanthine oxidoreductase (XOR) mediated degradation of purine metabolites. Analysis of pro-oxidant activity of the enzymatic complex XOR and its constituents, xanthine oxidase (XO) and xanthine dehydrogenase (XDG), is an issue of considerable interest in this context.Objectives:Evaluation of XO and XDG activities in RF-positive and RF-negative RA using both plasma and lysed lymphocyte samples.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. Diagnosis of RA had been verified using ACR/EULAR 2010 criteria. Enzymatic activities in plasma and lymphocytes were measured spectrophotometrically and expressed as nmol/min/ml. Enzymatic activities in lymphocytes were also normalized to 1×107 cells/ml. Statististical tests were selected in line with common guidelines. Differences were considered significant when p<0.05. Reference ranges were calculated as means ±2SD.Results:75 adult RA patients (52 females and 23 males, mean age 43.9±0.97 years, mean disease duration 8.5±0.3 years) from the rheumatology unit of Volgograd Clinical Emergency Hospital #25 as well as 35 healthy controls were included in the study. RF-positive RA and RF-negative RA were observed in 49 (65.3%) and 26 (34.7%) patients, respectively. Reference ranges for plasma and lymphocyte XO activities were 2.60-3.96 and 14.2-27.8 nmol/min/ml, respectively. Similar ranges for XDG activities were 4.49-5.93 and 22.5-40.7 nmol/min/ml, respectively. Enzymatic profile of RA patients is characterized by significantly increased XO activity in plasma and decreased XO and XDG activities in lymphocytes (р<0.001). XO activity is increased (p<0.001), XDG activity is decreased (p<0.001) in blood plasma of patients with RF-negative RA, while the activity of both enzymes is decreased in lymphocytes (p<0.001). XO activity (p<0.001) and XDG activity (p<0.05) is increased in blood plasma, XO activity and XDG activity are decreased (p<0.001) in lymphocytes of patients with RF-positive RA. Plasma XO and XDG activities are also higher, and lymphocyte XO and XDG activities are lower in patients with RF-positive RA than in patients with RF-negative RA (р<0.001).Conclusion:Our study revealed the relationship between enzyme parameters and rheumatoid factor presence. More pronounced changes in the enzyme activities were observed in patients with RF-positive RA. These results demonstrate that activation of the xanthine oxidase/xanthine dehydrogenase enzyme complex is an substantial factor of induction and continuation of the autoimmune rheumatoid inflammation.Disclosure of Interests:None declared
Identification of xanthine dehydrogenase/xanthine oxidase as a rat Paneth cell zinc-binding protein