关键词: Exosomes MicroRNAs Plasma Rheumatoid Arthritis

Mesh : Humans Arthritis, Rheumatoid / blood genetics immunology Exosomes MicroRNAs / blood Female Male Middle Aged B-Lymphocytes / immunology Case-Control Studies Adult Biomarkers / blood ROC Curve Real-Time Polymerase Chain Reaction

来  源:   DOI:10.1016/j.clinsp.2024.100441   PDF(Pubmed)

Abstract:
This study aimed to identify differentially expressed microRNAs (miRNAs) in exosomes derived from the blood plasma of Rheumatoid Arthritis (RA) patients and explore their clinical significance and biological roles.
Illumina high-throughput sequencing was employed to measure miRNA expression levels in plasma exosomes, followed by validation using qRT-PCR. The correlation between exosomal miRNAs and disease activity was systematically analyzed. Additionally, the pathogenic effects of RA exosomes were investigated through bioinformatics analysis and in vitro experiments.
Significantly reduced levels of exosomal miR-144-3p and miR-30b-5p were observed in RA patients, which were negatively correlated with DAS28 scores and anti-CCP antibody levels. ROC curve analysis showed that miR-144-3p and miR-30b-5p in plasma exosomes could effectively distinguish RA patients from healthy controls, with AUC values of 0.725 and 0.773, respectively. Combining bioinformatics analysis and in vitro experiments, it was demonstrated that plasma exosomes contribute to ongoing autoantibody production in RA by promoting B-cell differentiation and antibody production.
The present study indicates that plasma exosomes from RA patients may be potentially pathogenic. Exosomal miR-144-3p and miR-30b-5p exhibit significant decreases in RA patients and are associated with disease activity, suggesting their potential as valuable biomarkers for RA.
摘要:
本研究旨在鉴定类风湿关节炎(RA)患者血浆外泌体中差异表达的microRNAs(miRNAs),并探讨其临床意义和生物学作用。
Illumina高通量测序用于测量血浆外泌体中的miRNA表达水平,然后使用qRT-PCR进行验证。系统分析了外泌体miRNAs与疾病活动的相关性。此外,通过生物信息学分析和体外实验研究了RA外泌体的致病作用。
在RA患者中观察到外泌体miR-144-3p和miR-30b-5p水平显著降低,与DAS28评分和抗CCP抗体水平呈负相关。ROC曲线分析显示血浆外泌体中miR-144-3p和miR-30b-5p能有效区分RA患者和健康对照,AUC值分别为0.725和0.773。结合生物信息学分析和体外实验,研究表明,血浆外泌体通过促进B细胞分化和抗体产生,有助于RA持续产生自身抗体.
本研究表明,来自RA患者的血浆外泌体可能具有潜在的致病性。外泌体miR-144-3p和miR-30b-5p在RA患者中表现出显著下降,并与疾病活动相关,提示它们作为RA有价值的生物标志物的潜力。
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