First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, Athens, Greece; Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
First Department of Propaedeutic Internal Medicine and Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Clin Immunol. 2019 Jun;203:28-36. doi: 10.1016/j.clim.2019.03.009. Epub 2019 Mar 28.
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.
我们研究了 18 例活动期类风湿关节炎患者的 DNA 损伤反应和修复网络，并验证了治疗会影响该网络的假说。与对照组相比，患者来源的外周血单个核细胞中内源性 DNA 损伤（单链和双链断裂）增加了 3 倍（碱性彗星试验；平均 ± 标准差 Olive Tail Moment 为 11.8 ± 7.3 比 4.3 ± 2.2，p < .001）。与对照组相比，患者的 DNA 损伤形成（氧化应激和碱基缺失）、全基因组修复能力缺陷和更浓缩的染色质结构明显更高。在治疗 12 周后，所有 8 例检查的患者中染色质结构变松，全基因组修复能力恢复，氧化应激和碱基缺失减少，内源性 DNA 损伤水平达到对照值。我们得出结论，染色质结构紊乱、DNA 修复能力缺陷以及 DNA 损伤形成增加，这些在治疗后是可逆的，导致类风湿关节炎中内源性 DNA 损伤的积累。
