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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2017

Open Access 01-12-2017 | Research article

Circulating DNA in rheumatoid arthritis: pathological changes and association with clinically used serological markers

Authors: Elena Rykova, Aleksey Sizikov, Dirk Roggenbuck, Oksana Antonenko, Leonid Bryzgalov, Evgeniy Morozkin, Kseniya Skvortsova, Valentin Vlassov, Pavel Laktionov, Vladimir Kozlov

Published in: Arthritis Research & Therapy | Issue 1/2017

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Abstract

Background

Early diagnosis of rheumatoid arthritis (RA) is crucial to providing effective therapy and often hampered by unspecific clinical manifestations. Elevated levels of extracellular circulating DNA (cirDNA) in patients with autoimmune disease were found to be associated with etiopathogenesis. To our knowledge, this is the first study to investigate the putative diagnostic use of cirDNA in RA and its association with disease activity.

Methods

Blood samples were taken from 63 healthy subjects (HS) and 74 patients with RA. cirDNA was extracted from plasma and cell surface-bound cirDNA fractions (csbDNA). cirDNA concentration was measured by quantitative real-time polymerase chain reaction. Rheumatoid factor was analyzed by immunonephelometry, whereas C-reactive protein and anticitrullinated protein/peptide antibodies (ACPA) were detected by enzyme-linked immunosorbent assay.

Results

Plasma cirDNA was significantly elevated in patients with RA compared with HS (12.0 versus 8.4 ng/ml, p < 0.01). In contrast, nuclear csbDNA (n-csbDNA) was significantly decreased (24.0 versus 50.8 ng/ml, p < 0.01), whereas mitochondrial csbDNA (m-csbDNA) was elevated (1.44 × 106 copies/ml versus 0.58 × 106 copies/ml, p < 0.05) in RA. The combination of csbDNA (mitochondrial + nuclear) with ACPA reveals the best positive/negative likelihood ratios (LRs) for the discrimination RA from HS (LR+ 61.00, LR− 0.03) in contrast to ACPA (LR+ 9.00, LR− 0.19) or csbDNA (LR+ 8.00, LR− 0.18) alone.

Conclusions

Nuclear and mitochondrial cirDNA levels in plasma and on the surface of blood cells are modulated in RA. Combination of cirDNA values with ACPA can improve the serological diagnosis of RA.
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Metadata
Title
Circulating DNA in rheumatoid arthritis: pathological changes and association with clinically used serological markers
Authors
Elena Rykova
Aleksey Sizikov
Dirk Roggenbuck
Oksana Antonenko
Leonid Bryzgalov
Evgeniy Morozkin
Kseniya Skvortsova
Valentin Vlassov
Pavel Laktionov
Vladimir Kozlov
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2017
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-017-1295-z

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