scholarly journals AB0049 RELATIONSHIP OF RHEUMATOID FACTOR AND XANTHINE OXIDOREDUCTASE ENZYMATIC CONSTITUENTS IN SEVERAL BLOOD COMPARTMENTS OF RHEUMATOID ARTHRITIC PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1057.1-1057
Author(s):  
S. Bedina ◽  
A. Trofimenko ◽  
E. Mozgovaya ◽  
M. Mamus ◽  
S. Spitsina
Keyword(s):  
Blood Plasma ◽  
Rheumatoid Factor ◽  
Xanthine Oxidase ◽  
Xanthine Dehydrogenase ◽  
Enzymatic Activities ◽  
Systemic Autoimmune Disease ◽  
Ros Generation ◽  
Reference Ranges ◽  
Xanthine Oxidoreductase ◽  
In Blood Plasma

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

Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase

FEBS Journal ◽  
2008 ◽  
Vol 275 (13) ◽  
pp. 3278-3289 ◽  
Author(s):  
Tomoko Nishino ◽  
Ken Okamoto ◽  
Bryan T. Eger ◽  
Emil F. Pai ◽  
Takeshi Nishino
Keyword(s):  
Xanthine Oxidase ◽  
Xanthine Dehydrogenase ◽  
Xanthine Oxidoreductase

scholarly journals Xanthine oxidase and xanthine dehydrogenase activity in rheumatoid arthritis: the enzyme profile of blood plasma

2018 ◽  
Author(s):  
S. A. Bedina ◽  
E. E. Mozgovaia ◽  
E. A. Tikhomirova ◽  
M. A. Mamus ◽  
S. S. Dotsenko ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Plasma ◽  
Xanthine Oxidase ◽  
Dehydrogenase Activity ◽  
Xanthine Dehydrogenase ◽  
Enzyme Profile

scholarly journals AB0841 ALTERED XANTHINE OXIDASE AND XANTHINE DEHYDROGENASE ACTIVITIES IN RED BLOOD CELLS AS A CONTRIBUTION TO AUTOIMMUNE ANEMIA APPEARANCE IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1444.1-1444
Author(s):  
E. Mozgovaya ◽  
A. Trofimenko ◽  
S. Bedina ◽  
S. Spitsina ◽  
M. Mamus ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Oxygen Species ◽  
Red Blood Cells ◽  
Xanthine Oxidase ◽  
Blood Cells ◽  
Reactive Oxygen ◽  
Xanthine Dehydrogenase ◽  
Enzymatic Activities ◽  
Oxygen Species ◽  
Metabolism Enzymes

Background:Rheumatoid arthritis (RA) is severe autoimmune joint disease, accompanied by a wide variety of extra-articular manifestations. Anemia is one of the most common organ involvements in RA, being diagnosed in 36-65% patients. Iron metabolism alterations, shortened RBC lifespan, and impaired erythropoiesis in bone marrow are believed to play a leading role in RA-related anemia development. These processes in RA can be mediated by increased effect of proinflammatory cytokines, including IFNγ and TNFα, and similar mechanisms could contribute to high xanthine oxidoreductase (XOR) expression. This enzyme makes multiple pathophysiological effects, some of which can be related to the development of anemia in RA. Reactive oxygen species generated by XOR are capable, in particular, of damaging cell membranes, exerting influence on iron mobilization from ferritin in liver, and inducing changes in intestinal iron absorption.Objectives:Evaluation of changes in XOR interconvertible forms (xanthine oxidase and xanthine dehydrogenase) activities in RBC of RA patients.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 75 RA patients with verified RA were enrolled in the study. The diagnosis was verified using the ACR/EULAR criteria (2010). The reference group consisted of 35 healthy individuals. Хanthine oxidase (XO, ЕС 1.17.3.2) and xanthine dehydrogenase (XDG, ЕС 1.17.1.4) activities were measured in lysed red blood cells by spectrophotometric method as previously described [1]. The enzymatic activities were expressed as nmol/min/ml and normalized to 1×109 cells/ml. Statistical comparison tests were selected in according to common guidelines. Central tendencies were expressed as means±SEM. Differences were considered significant when p<0.05.Results:Mean age of RA patients was 43.9±0.97 years, and mean RA duration was 8.5±0.3 years. Extra-articular manifestations were diagnosed in 32 (42.7%) RA patients and 17 (53.1%) of them had anemia. We revealed substantial changes in XO and XDG activities in lysed RBC of RA patients with anemia. Increased XO activity and decreased XDG activity were observed in comparison with healthy controls (р<0.001 for both enzymes). In parallel with the increase in DAS28 index, significant growth of XOD/XDG coefficient was observed, which was caused by both XOD activity elevation and XDG activity reduction in lysed RBC (p<0.001 for both enzymes). Enzymatic activities depended also on the extra-articular RA manifestations. Mean XO activity was higher and mean XDG activity were lower in patients with extra-articular manifestations (p<0.05 for both enzymes), but the extent of changes was substantially less comparing to anemia.Conclusion:Autoimmune inflammation in RA is accompanied by changes in enzymatic activities of XOR interconvertible forms and their ratio. Transformation of XDG into КО ultimately leads to significant increase in the generation of reactive oxygen species that have a damaging effect on lipids, proteins and other cellular components, and specifically in RBC. This fact may be one of the reasons for their premature damage and development of anemia in RA.References:[1]Zborovskaya I.A., et al. Influence of analgetics on plasma and lymphocytic activity of the purine metabolism enzymes in rheumatoid arthritis patients. Russian Journal of Pain 2018;3:47Disclosure of Interests:None declared

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