Anti-cytokine therapy and plasma DNA in patients with rheumatoid arthritis
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.
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).
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.
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.
KeywordsCell-free DNA DAMPs Innate immunity Biological therapy Immunosuppressive treatment
This study was supported by the Ministry of Education of the Slovak Republic (VEGA 1/0156/17, VEGA 1/0092/17 and APVV-16-0273).
PC, BV, EŠ and VM designed and directed the study; LL, BV, and BK isolated and quantified DNA from plasma samples; LL analyzed the data; PC and LL wrote the article.
This study was funded by the Ministry of Education of the Slovak Republic (VEGA 1/0156/17).
Compliance with ethical standards
Conflict of interest
Lucia Lauková declares that there is no conflict of interest regarding the publication of this article. Barbora Konečná declares that there is no conflict of interest regarding the publication of this article. Barbora Vlková declares that there is no conflict of interest regarding the publication of this article. Vanda Mlynáriková declares that there is no conflict of interest regarding the publication of this article. Peter Celec declares that there is no conflict of interest regarding the publication of this article. Emőke Šteňová declares that there is no conflict of interest regarding the publication of this article.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Number of ethical approval: ICH GCP 135/95, date: 13.06.2016. Name of approving institution: Ethics Committee of University Hospital and Faculty of Medicine in Bratislava.
Informed consent was obtained from all individual participants included in the study.
- 5.Sur Chowdhury C, Giaglis S, Walker UA et al (2014) Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis Res Ther 16:R122. https://doi.org/10.1186/ar4579 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Singh JA, Hossain A, Tanjong Ghogomu E et al (2016) Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis. Cochrane Database Syst Rev 13:CD012183. https://doi.org/10.1002/14651858.CD012183 Google Scholar