POS1206 ORIGIN AND DIAGNOSTIC POTENTIAL OF EXTRACELLULAR DNA IN RHEUMATOID ARTHRITIS

• Published in: Annals of the rheumatic diseases Vol. 83; no. Suppl 1; p. 740
• Main Authors: Lehmann, J., Giaglis, S., Kyburz, D., Daoudlarian, D., Walker, U.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2024; Elsevier Limited
• Subjects: Antineutrophil cytoplasmic antibodies; Biomarkers; Blood donors; Decision making; Diagnostic test; Inflammation; Innate immunity; Leukocytes (neutrophilic); Mitochondrial DNA; Patients; Plasma; Remission; Rheumatoid arthritis; Rheumatoid factor; Rheumatology; Scientific Abstracts
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2024-eular.4939

Background:Neutrophil extracellular trap formation and cell-free DNA (cfDNA) contribute to the inflammation in rheumatoid arthritis (RA).Objectives:To investigate if mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) is more abundant in the circulation of RA patients and to explore if DNA concentration measurements may assist in clinical decision-making.Methods:This single-centre prospective observational study collected plasma from consecutive RA patients and healthy blood donors. Platelets were removed, and mtDNA and nDNA copy numbers were quantified by PCR.Results:106 RA patients (median DAS28-ESR 2.5, clinical disease activity index (CDAI) 6.0) and 85 healthy controls (HC) were recruited. Circulating median mtDNA copy numbers were increased 19.4-fold in the plasma of patients with RA (median 1.1 x108 copies/mL) compared to HC (median 5.4 x106 copies/mL, p<0.0001). Receiver operating characteristics curve analysis of mtDNA copy numbers identified RA patients with high sensitivity (92.5%) and specificity (89.4%) among all 191 study subjects (area under the curve 0.97, p <0.0001, with a positive likelihood ratio of 8.7). mtDNA copy numbers also discriminated RA in remission from HC (p<0.0001). Similar analyses showed no significance for nDNA.Demographic, serological (rheumatoid factor positivity, ACPA-positivity) and treatment factors were not associated with DNA concentrations. mtDNA plasma concentrations, however, correlated significantly with DAS-ESR and increased numerically with increasing DAS28-ESR and CDAI activity.Conclusion:In contrast to nDNA, mtDNA is significantly elevated in the plasma of RA patients compared with HC. Regardless of RA activity, the abundance of circulating mtDNA is a sensitive discriminator between RA patients and HC.REFERENCES:[1] Giaglis S, et al. Mitochondrial DNA: a novel indicator of active inflammation in ANCA-associated vasculitides. Rheumatology (Oxford) 2023; 62: 2930 – 7Acknowledgements:We thank all patients participating in this study and are grateful for the support of our colleagues and health care practitioners.Disclosure of Interests:Julia Lehmann: None declared, Stavros Giaglis: None declared, Diego Kyburz Not relevant to this work, Douglas Daoudlarian: None declared, Ulrich Walker Not relevant to this work