AB0637 THE RELATIONSHIP OF NITRIC OXIDE LEVELS, PEPTIDYL ARGININE DEIMINASE-4 AND ARGINASE-1 ACTIVITY WITH RADIOGRAPHIC PROGRESSION IN PATIENTS WITH NEWLY DIAGNOSED RHEUMATOID ARTHRITIS AFTER TWO YEARS OF FOLLOW-UP
Authors: J. Cvetkovic, S. Stojanović, B. Stamenkovic, T. Jevtovic Stoimenov, J. Basic, I. Aleksic Milenkovic, J. Jocic, N. Dimic
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a variable clinical course. Excessive production of nitric oxide (NO) potentiates the autoimmune response, promotes synovial inflammation and increases oxidative stress resulting in bone erosion and cartilage destruction. NO is increased in patients with RA and is accompanied by compensatory low values of arginase-1 enzyme activity, bearing in mind that the amino acid arginine is a common substrate for arginase-1 and nitric oxide synthase that synthesizes NO. The enzyme peptidyl arginine deiminase-4 (PAD4) catalyzes the reaction of protein citrullination, which initiates and maintains the immune response by producing anti-citrulline antibodies (ACPA), which are a specific marker for the diagnosis of RA and are associated with a more progressive form of the disease. Radiographic progression is an individual process in patients with RA and may be independent of disease activity measured by known indices, so it is necessary to find new early markers of a more aggressive form of RA. <h3>Objectives:</h3> To examine the difference in NO levels and arginase-1 and PAD4 activity at disease onset in those who had radiographic progression after two years and those who did not. To examine the association of NO levels and arginase-1 and PAD4 activity with the development of radiographic progression after two years of treatment according to the "treat to target" (T2T) protocol. <h3>Methods:</h3> A total of 35 patients were examined and analyzed. All patients had RA and were treated in the period from 2016-2019 at the Institute "Niška Banja" at the time of diagnosis, and after two years of treatment. The activity of PAD4 and arginase-1 was determined by ELISA and the level of NO by colorimetric detection with Griess reagent. Radiographic progression was measured by the Sharp score and quantified if present. From the statistical analyses the Mann–Whitney U test and univariate logistic regression analysis were used. All statistical analyzes were performed using SPSS version 18.0 software (SPSS, Chicago, IL, USA) for Windows. <h3>Results:</h3> A total of 33 women, average age 58.5 years (min30, max77) were observed uder this study. All patients were treated with the drug methotrexate in an average dose of 15 mg per week (min 10, max 20) according to the T2T protocol. Study determined that 12 of them (34.3%) had radiographic progression after two years of treatment. NO values were lower and PAD4 and arginase-1 activity were higher in patients with radiographic progression compared to those without, but there was no statistical significance (Table 1). Univariate logistic regression showed that there was no statistically significant association between NO levels, PAD4 and arginase-1 activity at the beginning of the disease and radiographic progression after two years of follow-up (Table 2). <h3>Conclusion:</h3> The results of our study did not show an association of NO levels, PAD4 and arginase-1 activity at the beginning of RA treatment with radiographic progression after two years of follow-up. Additional research is needed to examine the values of these enzymes and NO after starting and during RA treatment, and their association with the development of radiographic progression. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>