The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis
Abstract Rheumatoid arthritis (RA) as a chronic autoimmune inflammatory disease increases extracellular DNA (ecDNA). Our previous study has shown that anti-inflammatory treatment reduces ecDNA, but it is unclear whether there is an association with treatment response. The aim of this study was to an...
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| Format: | Article |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-23954-8 |
| _version_ | 1811189033401843712 |
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| author | Kristína Macáková Júlia Illésová Vanda Mlynáriková Alexandra Lesayová Barbora Konečná Barbora Vlková Peter Celec Emöke Šteňová |
| author_facet | Kristína Macáková Júlia Illésová Vanda Mlynáriková Alexandra Lesayová Barbora Konečná Barbora Vlková Peter Celec Emöke Šteňová |
| author_sort | Kristína Macáková |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA) as a chronic autoimmune inflammatory disease increases extracellular DNA (ecDNA). Our previous study has shown that anti-inflammatory treatment reduces ecDNA, but it is unclear whether there is an association with treatment response. The aim of this study was to analyze the changes of ecDNA induced by biological disease-modifying antirheumatic drugs (bDMARDs) in RA patients with an emphasis on the subcellular origin of ecDNA. Plasma samples from 40 RA patients were collected in three different time-points: before treatment with bDMARDs as well as 3 and 12 months following treatment initiation. Total, nuclear and mitochondrial ecDNA was quantified using fluorometry and real-time PCR. Disease activity score (DAS28) and C-reactive protein (CRP) were used to monitor the clinical status and the response to treatment. Treatment with bDMARDs elicited an overall improvement of the clinical status: DAS28 and CRP showed a significant decrease by 54% and 43%, respectively, after 3 months of treatment. A significant decrease of total ecDNA by 60% and nuclear ecDNA by 58% was detected only in good responders after 3 months of bDMARDs treatment. No significant changes of plasma ecDNA concentration were observed in moderate and non-responders. Deoxyribonuclease activity was not affected by the treatment. None of the analyzed biomarkers differed between the groups at baseline. Plasma ecDNA especially of nuclear origin could potentially be useful to monitor the treatment response in RA. Further studies should shed light on disease-treatment interplay implicated in ecDNA origin potentially linked to neutrophil extracellular traps. |
| first_indexed | 2024-04-11T14:28:08Z |
| format | Article |
| id | doaj.art-be794b3d4718497cbd7c02a555c40ef9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:28:08Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-be794b3d4718497cbd7c02a555c40ef92022-12-22T04:18:47ZengNature PortfolioScientific Reports2045-23222022-12-0112111010.1038/s41598-022-23954-8The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritisKristína Macáková0Júlia Illésová1Vanda Mlynáriková2Alexandra Lesayová3Barbora Konečná4Barbora Vlková5Peter Celec6Emöke Šteňová7Institute of Molecular Biomedicine, Faculty of Medicine, Comenius UniversityInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius UniversityNational Institute of Rheumatic DiseasesEdinburgh Medical School: Biomedical Sciences, University of EdinburghInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius UniversityInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius UniversityInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University1st Department of Internal Medicine, Faculty of Medicine, University Hospital, Comenius UniversityAbstract Rheumatoid arthritis (RA) as a chronic autoimmune inflammatory disease increases extracellular DNA (ecDNA). Our previous study has shown that anti-inflammatory treatment reduces ecDNA, but it is unclear whether there is an association with treatment response. The aim of this study was to analyze the changes of ecDNA induced by biological disease-modifying antirheumatic drugs (bDMARDs) in RA patients with an emphasis on the subcellular origin of ecDNA. Plasma samples from 40 RA patients were collected in three different time-points: before treatment with bDMARDs as well as 3 and 12 months following treatment initiation. Total, nuclear and mitochondrial ecDNA was quantified using fluorometry and real-time PCR. Disease activity score (DAS28) and C-reactive protein (CRP) were used to monitor the clinical status and the response to treatment. Treatment with bDMARDs elicited an overall improvement of the clinical status: DAS28 and CRP showed a significant decrease by 54% and 43%, respectively, after 3 months of treatment. A significant decrease of total ecDNA by 60% and nuclear ecDNA by 58% was detected only in good responders after 3 months of bDMARDs treatment. No significant changes of plasma ecDNA concentration were observed in moderate and non-responders. Deoxyribonuclease activity was not affected by the treatment. None of the analyzed biomarkers differed between the groups at baseline. Plasma ecDNA especially of nuclear origin could potentially be useful to monitor the treatment response in RA. Further studies should shed light on disease-treatment interplay implicated in ecDNA origin potentially linked to neutrophil extracellular traps.https://doi.org/10.1038/s41598-022-23954-8 |
| spellingShingle | Kristína Macáková Júlia Illésová Vanda Mlynáriková Alexandra Lesayová Barbora Konečná Barbora Vlková Peter Celec Emöke Šteňová The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis Scientific Reports |
| title | The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis |
| title_full | The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis |
| title_fullStr | The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis |
| title_full_unstemmed | The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis |
| title_short | The dynamics of extracellular DNA associates with treatment response in patients with rheumatoid arthritis |
| title_sort | dynamics of extracellular dna associates with treatment response in patients with rheumatoid arthritis |
| url | https://doi.org/10.1038/s41598-022-23954-8 |
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