UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair.

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY
Mutagenesis Pub Date : 2021-11-29 DOI:10.1093/mutage/geab036
Consuelo Micheli, Alice Parma, Chiara Tani, Domenica Di Bello, Aurora Falaschi, Anna Chiaramonte, Serena Testi, Marta Mosca, Roberto Scarpato
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引用次数: 2

Abstract

Immunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY 581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterize SLE and UCTD, aiming to improve the treatment plan and the quality of the patients' life.
UCTD和SLE患者表现出氧化和DNA损伤水平增加,同时DSB修复动力学改变。
免疫耐受是免疫系统的一个重要特征;它的丢失可能导致淋巴细胞的异常反应,从而引起自身免疫性疾病。结缔组织病(CTD)是自身免疫性疾病中最重要的一类疾病。CTD被归类为系统性风湿病,包括系统性红斑狼疮(SLE)和未分化CTD (UCTD)等病理。在这项研究中,我们评估了SLE和UCTD患者外周血淋巴细胞的氧化和基因组损伤,并根据疾病活动性和血清学特征的存在/缺失进一步分类。用荧光脂肪酸类似物BODIPY581/591 C11评价细胞膜的氧化损伤。SLE和UCTD患者的氧化淋巴细胞百分比均高于对照组,氧化应激与疾病活动性和自身抗体谱呈正相关。采用γ - h2ax聚焦法定量测定自发性双链断裂(DSBs)的存在,并评估T细胞经丝裂霉素C (MMC)处理后DSBs修复系统的能力。患有这些自身免疫性疾病的受试者比健康对照组显示出更多的γ - h2ax病灶,但与疾病活动性和血清学特征没有相关性。此外,患者对mmc诱导的DSBs表现出改变的反应,导致其周围细胞凋亡大大增加。综上所述,我们的研究结果证实了氧化应激、DNA损伤和DNA修复受损之间的相互作用,这与疾病的侵袭性和临床进展直接相关。我们建议对这些分子标志物进行评估,以更好地表征SLE和UCTD,旨在改善治疗方案和患者的生活质量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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