AB1333 CELL-FREE DNA AND BIOLOGICAL TREATMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Vanda Mlynarikova, Frantisek Malis, Peter Celec, Barbora Vlkova, Emoke Stenova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cell free DNA (cfDNA) are DNA fragments released from the cell nucleus into extracellular compartment and is therefore detectible in plasma or serum. The most common reason for this release is tissue damage, cell death and inflammation of diverse origin. In regard to autoimmune diseases, increased levels of cfDNA has been found in plasma/serum in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome. The results of some published works, appointing the correlation between levels of cfDNA and RA activity, are controversial, that's why the position of cfDNA as a potential new biomarker remains unclear. <h3>Objectives</h3> The aim of our study was to describe the effect of biological therapy on the concentration of cfDNA and explore the correlation between therapeutic response DAS28 score and cfDNA levels. This potential correlation could define cfDNA as a new marker of treatment response and also potentially also clarify the role of cfDNA in the pathogenesis of RA. <h3>Methods</h3> Plasma samples of 40 patients with RA were collected before, as well as 3 and 12 months after starting treatment with tumor necrosis factor α- inhibitor (TNFα-inhibitor). Total cfDNA was quantified fluorometrically. Treatment response was evaluated by using DAS 28 scoring system and C-reactive protein. <h3>Results</h3> The treatment with TNFα-inhibitors showed statistically significant changes of DAS28 and cfDNA. According the EULAR treatment response defined by DAS28 changes, patients with good response showed statistically significant decrease of cfDNA in month 3 (p&lt;0,005), but the improvement in month 12 was just on the border of statistical significance (p=0,059). There were also only slight changes in group with moderate DAS 28 response in month 12 (p=0,054). In the entire group there was found slight positive (r =0,44), statistically significant (p=0,0073) correlation between the levels of cfDNA and DAS 28 score after 12 month of treatment. <h3>Conclusion</h3> Even if treatment with TNFα-inhibitors decreases plasma cfDNA, there are other markers with better correlation with disease activity. We consider, that the changes in cfDNA levels after biological treatment could determine the role cfDNA more as a consequence of the inflammation, rather than the cause of inflammation in this autoimmune disease, but further research is needed. <h3>References</h3> [1] 1. Zhong XY, von Mühlenen I, Li Y, et al. Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis. Clin Chem 2007 53(9):1609-1614. [2] Dunaeva M, Buddingh BC, Toes REM, et al. Decreased serum cell free DNA levels in rheumatoid arthritis. Auto Immun Highlights 2015 6(1-2): 23-30. [3] Abdelal IT, Zakaria MA, Sharaf DM, et al. Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systematic lupus erythematosus patients. The Egyptian Rheumatologist 2016 38:295-300. [4] Hashimoto T, Yoshida K, Hashimoto N, et al. Circulating Cell Free DNA: A Marker To Predict The Therapeutic Response for Biological Dmards in Rheumatoid Arthritis. Int J Rheum Dis2017;20(6):722-730. [5] Laukova L, Konečná B, Vlková B, et al. Anti-cytokine therapy and plasma DNA in patients with rheumatoid arthritis. Rhematol Int2018;38 (8):1449-1454. <h3>Disclosure of Interests</h3> None declared