免疫老化的具体特征是在类风湿关节炎发展的早期阶段检测到的。

IF 10.8 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
EBioMedicine Pub Date : 2025-09-01 Epub Date: 2025-09-03 DOI:10.1016/j.ebiom.2025.105900
Karim Raza, Archana Sharma-Oates, Leonid Padyukov, Annette H M van der Helm-van Mil, Arthur G Pratt, Simon W Jones, A Filer, Janet M Lord, Niharika A Duggal
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引用次数: 0

摘要

背景:类风湿关节炎是一种与年龄相关的疾病,表现为免疫系统老化的特征。本研究旨在确定在RA发展的早期阶段免疫老化的过早存在,包括临床疑似关节痛和未分化关节炎的患者。方法:我们招募了224名参与者:69名健康对照者(平均年龄57.12岁,男性28%);临床怀疑关节痛32例(平均年龄46.50岁,男性占11%);未分化关节炎44例(平均年龄51.96岁,男性占21%);23例新出现的DMARD幼稚型RA症状持续时间不超过3个月(平均年龄56.5岁,30%男性),56例DMARD幼稚型RA症状持续时间大于3个月(平均年龄56.41岁,41%男性)。通过流式细胞术评估免疫衰老的特征,并使用8种免疫细胞类型频率的子集来生成免疫衰老IMM-AGE的综合评分,并对免疫衰老的特征进行转录组学分析。结果:在关节痛或未分化性关节炎患者中,初始CD4 T细胞和近期胸腺移植物的频率降低。免疫老化的其他特征,如Th17, Tregs和衰老样T细胞的频率升高,只有在RA建立后才会看到。总体而言,IMM-AGE评分和其他衰老标志(炎症、自噬缺陷)在疾病早期阶段患者中升高。最后,我们提供了免疫老化特征作为关节炎患者RA发展的预测因子的证据。解释:我们已经证明,免疫老化的一些特征存在于RA的早期阶段,因此可能有助于疾病的发展。未来的研究应该确定老年保护药物如亚精胺(自噬增强剂)、抗衰老药(清除衰老细胞)和二甲双胍(减轻炎症和促进自噬)是否能减少RA风险患者的疾病进展。资助:本研究由FOREUM和欧洲抗风湿病联盟(EULAR)资助。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Specific features of immune ageing are detected in the earliest stages in rheumatoid arthritis development.

Background: Rheumatoid arthritis is an age-related disease displaying features of an aged immune system. This study aims to determine premature presence of immune ageing in the early stages of RA development, including in patients with clinically suspected arthralgia and undifferentiated arthritis.

Methods: We recruited 224 participants: 69 healthy controls (mean age 57.12 years, 28% male); 32 with clinically suspected arthralgia (mean age 46.50 years, 11% male); 44 with undifferentiated arthritis (mean age 51.96 years, 21% male); 23 with newly presenting DMARD naive RA and 3 months or less symptom duration (mean age 56.5 years, 30% male) and 56 with DMARD naive RA and greater than 3 months symptom duration (mean age 56.41 years, 41% male). Features of immune ageing were assessed via flow cytometry and a subset of 8 immune cell type frequencies were used to generate an integrated score of immune ageing IMM-AGE and transcriptomic analysis for hallmarks of immune ageing was performed.

Findings: Reduced frequencies of naive CD4 T cells and recent thymic emigrants were seen in patients with arthralgia or undifferentiated arthritis. Other features of immune ageing, such as raised frequency of Th17, Tregs and senescent-like T cells, were only seen once RA was established. Overall, the IMM-AGE score and other hallmarks of ageing (inflammation, autophagic defects) were raised in patients during early stages of the disease. Lastly, we have provided evidence of immune ageing features as a predictor of RA development in arthralgia patients.

Interpretation: We have shown that some features of immune ageing are present in the very early stages of RA and may therefore contribute to disease development. Future research should determine whether geroprotective drugs such as spermidine (autophagy booster), senolytics (clearance of senescent cells) and metformin (attenuates inflammation and boosts autophagy) reduce progression of the disease in patients at risk of RA.

Funding: This study was funded by a grant from FOREUM and the European League Against Rheumatism (EULAR).

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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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