DNA damage accumulation, defective chromatin organization and deficient DNA repair capacity in patients with rheumatoid arthritis.
Antirheumatic treatment
Chromatin organization
DNA repair
Endogenous DNA damage
Oxidative stress
Rheumatoid arthritis
Journal
Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
12
03
2019
revised:
27
03
2019
accepted:
27
03
2019
pubmed:
2
4
2019
medline:
3
4
2020
entrez:
2
4
2019
Statut:
ppublish
Résumé
We investigated the DNA damage response and repair network in 18 patients with active rheumatoid arthritis and tested the hypothesis that treatment influences this network. A 3-fold increase of endogenous DNA damage (single- and double-strand breaks) was detected in patient-derived peripheral blood mononuclear cells than controls (alkaline comet assay; mean ± SD Olive Tail Moment of 11.8 ± 7.3 versus 4.3 ± 2.2, p < .001). Patients exhibited significantly higher formation of DNA damage (oxidative stress and abasic sites), deficient global genome repair and more condensed chromatin structure than controls. Twelve weeks following treatment, chromatin structure loosened, global genome repair capacity was restored, oxidative stress and abasic sites decreased and levels of endogenous DNA damage reached control values in all 8 patients examined. We conclude that deregulated chromatin organization, deficient DNA repair capacity and augmented formation of DNA damage, which are reversible after treatment, contribute to the accumulation of endogenous DNA damage in rheumatoid arthritis.
Identifiants
pubmed: 30930144
pii: S1521-6616(19)30126-3
doi: 10.1016/j.clim.2019.03.009
pii:
doi:
Substances chimiques
Chromatin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
28-36Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.