Lucia Lauková1, Barbora Konečná1, Barbora Vlková1, Vanda Mlynáriková2, Peter Celec3,4,5, Emőke Šteňová6. 1. Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08, Bratislava, Slovakia. 2. National Institute of Rheumatic Diseases, Piešťany, Slovakia. 3. Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08, Bratislava, Slovakia. petercelec@gmail.com. 4. Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia. petercelec@gmail.com. 5. Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia. petercelec@gmail.com. 6. 1st Department of Internal Medicine, Faculty of Medicine, University Hospital, Comenius University, Mickiewiczova 13, Bratislava, Slovakia.
Abstract
BACKGROUND: Extracellular DNA (ecDNA) is increased in inflammation and it also induces inflammation. In patients with rheumatoid arthritis (RA), plasma ecDNA is higher than in healthy controls. Due to low specificity, it cannot be used for screening, but it might be useful for monitoring and prognosis of therapy success. The effect of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) on plasma ecDNA in RA patients with regards to its subcellular origin has not been analyzed yet. The aim of this study was to describe the effects of bDMARDs on plasma ecDNA and its nuclear (nDNA) and mitochondrial (mtDNA) fractions in patients with RA. METHODS: Plasma samples of 32 patients with RA were collected before, as well as 3 and 6 months after starting the treatment with bDMARDs. Total plasma ecDNA was quantified fluorometrically. The subcellular origin of ecDNA was assessed using real time PCR. Treatment success was monitored using DAS28 and C-reactive protein (CRP). RESULTS: The clinical status of patients improved. Both DAS28 and CRP decreased by 52 and 73% after 3 months of treatment. Plasma ecDNA decreased significantly only after 6 months (by 26%). Real-time PCR showed that both, nDNA and mtDNA decreased by 63 and by 45% after 6 months. CONCLUSION: Treatment with bDMARDs decreases plasma ecDNA of both nuclear and mitochondrial origin. Dynamics of ecDNA is slower than dynamics of standard clinical markers. Therefore, it is likely to be not useful for monitoring of the disease progress, at least for RA.
BACKGROUND: Extracellular DNA (ecDNA) is increased in inflammation and it also induces inflammation. In patients with rheumatoid arthritis (RA), plasma ecDNA is higher than in healthy controls. Due to low specificity, it cannot be used for screening, but it might be useful for monitoring and prognosis of therapy success. The effect of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) on plasma ecDNA in RApatients with regards to its subcellular origin has not been analyzed yet. The aim of this study was to describe the effects of bDMARDs on plasma ecDNA and its nuclear (nDNA) and mitochondrial (mtDNA) fractions in patients with RA. METHODS: Plasma samples of 32 patients with RA were collected before, as well as 3 and 6 months after starting the treatment with bDMARDs. Total plasma ecDNA was quantified fluorometrically. The subcellular origin of ecDNA was assessed using real time PCR. Treatment success was monitored using DAS28 and C-reactive protein (CRP). RESULTS: The clinical status of patients improved. Both DAS28 and CRP decreased by 52 and 73% after 3 months of treatment. Plasma ecDNA decreased significantly only after 6 months (by 26%). Real-time PCR showed that both, nDNA and mtDNA decreased by 63 and by 45% after 6 months. CONCLUSION: Treatment with bDMARDs decreases plasma ecDNA of both nuclear and mitochondrial origin. Dynamics of ecDNA is slower than dynamics of standard clinical markers. Therefore, it is likely to be not useful for monitoring of the disease progress, at least for RA.
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