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干燥综合征患者唾液和血浆中线粒体RNA表达水平与干扰素特征基因表达及疾病活动的关联

Association of mitochondrial RNA expression levels in saliva and plasma with interferon signature gene expression and disease activity in patients with Sjögren disease.

作者信息

Ha You-Jung, Choi Yong Seok, Choi Se Rim, Yoon Jimin, Ku Doyeong, Kim Yoosik, Kang Eun Ha, Kim Keun-Suh, Jeong Woo-Jin, Hyon Joon Young, Cha Seunghee, Lee Yun Jong

机构信息

Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea (the Republic of).

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of).

出版信息

RMD Open. 2025 May 13;11(2):e005166. doi: 10.1136/rmdopen-2024-005166.

DOI:10.1136/rmdopen-2024-005166
PMID:40360431
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12083325/
Abstract

OBJECTIVE

To unveil the clinical implications of mitochondrial RNAs (mt-RNAs) in Sjögren disease (SjD), this study evaluated mt-RNA expression levels in the plasma and saliva of patients with SS and their association with SjD-related features.

METHODS

Plasma, saliva and/or peripheral blood mononuclear cells (PBMCs) were collected from 111 patients with SjD and 35 healthy controls (HCs), with 40 rheumatoid arthritis (RA) and 40 systemic lupus erythematosus (SLE) disease controls. The expression levels of mt-RNAs and interferon-stimulated genes (ISGs) were quantified by real-time PCR. Composite mt-RNA and ISG scores were calculated using logistic regression models. Their discriminative power was evaluated using receiver operating characteristic curve analyses, and correlations with clinical data were explored.

RESULTS

Altered mt-RNA expression in saliva or plasma and ISG expression in PBMCs were detected in patients with SjD, compared with HCs. Saliva and plasma mt-RNA scores showed better discriminative ability (area under the curve values=0.847 and 0.789, respectively) than ISG scores in distinguishing SjD from HCs. Plasma mt-RNA scores were significantly higher in patients with SjD than in those with RA and SLE (p<0.05). Saliva mt-RNA scores were positively associated with objective disease activity measures and Raynaud phenomenon in patients with SjD, whereas plasma mt-RNA scores did not show this association. RA and SLE disease activity correlated with plasma mt-RNA scores.

CONCLUSIONS

Extracellular mt-RNA burden is elevated in SjD, and mt-RNA scores effectively discriminated patients with SjD from HCs. Saliva mt-RNA levels were associated with SjD disease activity, suggesting their potential utility in disease monitoring and stratification of SjD.

摘要

目的

为揭示线粒体RNA(mt-RNA)在干燥综合征(SjD)中的临床意义,本研究评估了干燥综合征患者血浆和唾液中mt-RNA的表达水平及其与SjD相关特征的关联。

方法

收集了111例SjD患者、35例健康对照(HCs)、40例类风湿关节炎(RA)患者和40例系统性红斑狼疮(SLE)患者的血浆、唾液和/或外周血单个核细胞(PBMCs)。通过实时PCR定量mt-RNA和干扰素刺激基因(ISGs)的表达水平。使用逻辑回归模型计算复合mt-RNA和ISG评分。通过受试者工作特征曲线分析评估其判别能力,并探讨与临床数据的相关性。

结果

与HCs相比,SjD患者唾液或血浆中mt-RNA表达改变,PBMCs中ISG表达改变。在区分SjD与HCs方面,唾液和血浆mt-RNA评分显示出比ISG评分更好的判别能力(曲线下面积值分别为0.847和0.789)。SjD患者的血浆mt-RNA评分显著高于RA和SLE患者(p<0.05)。SjD患者的唾液mt-RNA评分与客观疾病活动指标和雷诺现象呈正相关,而血浆mt-RNA评分未显示这种关联。RA和SLE疾病活动与血浆mt-RNA评分相关。

结论

SjD患者细胞外mt-RNA负荷升高,mt-RNA评分可有效区分SjD患者与HCs。唾液mt-RNA水平与SjD疾病活动相关,提示其在SjD疾病监测和分层中的潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/bb09f58c9f00/rmdopen-11-2-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/2f83a3509ad1/rmdopen-11-2-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/033163d6dcd0/rmdopen-11-2-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/9cd42e3f6bd9/rmdopen-11-2-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/bb09f58c9f00/rmdopen-11-2-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/2f83a3509ad1/rmdopen-11-2-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/033163d6dcd0/rmdopen-11-2-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/9cd42e3f6bd9/rmdopen-11-2-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a57/12083325/bb09f58c9f00/rmdopen-11-2-g004.jpg

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本文引用的文献

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Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells.线粒体双链 RNA 释放到细胞质中是衰老细胞炎症表型的关键驱动因素。
Nat Commun. 2024 Aug 27;15(1):7378. doi: 10.1038/s41467-024-51363-0.
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RNA 5-methylcytosine marks mitochondrial double-stranded RNAs for degradation and cytosolic release.RNA 5-甲基胞嘧啶标记线粒体双链 RNA 进行降解并释放到细胞质中。
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Plasma mtDNA as a possible contributor to and biomarker of inflammation in rheumatoid arthritis.
血浆线粒体 DNA 作为类风湿关节炎炎症的潜在贡献因素和生物标志物。
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Identification of key mitochondria-related genes and their relevance to the immune system linking Parkinson's disease and primary Sjögren's syndrome through integrated bioinformatics analyses.通过综合生物信息学分析鉴定与帕金森病和原发性干燥综合征相关的关键线粒体相关基因及其与免疫系统的关联。
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Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases.先天免疫信号中的线粒体及其在自身免疫性疾病中的治疗意义。
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