首页 > 最新文献

Autoimmunity reviews最新文献

英文 中文
Treatment of pediatric chronic nonbacterial osteomyelitis - a systematic review. 儿童慢性非细菌性骨髓炎的治疗-一项系统综述。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-05 DOI: 10.1016/j.autrev.2026.104005
Sarah Turner, Eve Roberts, Natalie Hall, Christian M Hedrich

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease most commonly affecting children and young people. CNO can cause bone pain, hyperostosis and fractures, thereby significantly impacting on patients' wellbeing. The molecular pathophysiology of CNO is characterized by NLRP3 inflammasome activation and a pronounced imbalance between pro- and anti-inflammatory cytokines. In the absence of clinical trials, treatment of CNO remains empiric and is based on personal experience and published case series. This project systematically reviewed the available literature in pediatric CNO following 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) guidance accessing Medline, Embase, NCBI PubMed, Cochrane Library Clinical Trials, ClinicalTrials.gov, and WHO ICTRP. Nonsteroidal anti-inflammatory drugs are usually used as first-line treatment. They facilitate pain control and induce early remission in some patients but also associate with later flares. Conventional disease modifying antirheumatic drugs (DMARDs) have been used with mixed success and may be helpful in patients with associated arthritis, skin inflammation, and/or inflammatory bowel disease. Biologic DMARDs, namely TNF inhibitors, are effective for the treatment of bone and associated skin and/or bowel disease. Bisphosphonates induce rapid remission in most patients but may associate with higher relapse rates when compared to TNF inhibitors. The longstanding absence of diagnostic and, until recently, classification criteria as well as defined study endpoints, the small sample size and variable therapeutic approaches challenge interpretation of studies and comparisons between treatments. Prospective randomised controlled trials are urgently needed to improve the evidence base, resulting in approval of treatments for CNO.

慢性非细菌性骨髓炎(CNO)是一种自身炎症性骨病,最常见于儿童和年轻人。CNO可引起骨痛、骨质增生和骨折,从而严重影响患者的健康。CNO的分子病理生理特征是NLRP3炎性小体激活以及促炎性和抗炎性细胞因子之间的明显失衡。在缺乏临床试验的情况下,CNO的治疗仍然是经验性的,基于个人经验和已发表的病例系列。本项目根据“系统评价和荟萃分析的首选报告项目”(PRISMA)指南,系统地回顾了儿科CNO的现有文献,这些文献可访问Medline、Embase、NCBI PubMed、Cochrane图书馆临床试验、ClinicalTrials.gov和WHO ICTRP。非甾体类抗炎药通常作为一线治疗。它们有助于控制疼痛,并在一些患者中引起早期缓解,但也与后来的发作有关。传统的疾病调节抗风湿药物(DMARDs)的使用取得了不同程度的成功,可能对相关关节炎、皮肤炎症和/或炎症性肠病的患者有帮助。生物dmard,即TNF抑制剂,对骨和相关皮肤和/或肠道疾病的治疗有效。双膦酸盐在大多数患者中诱导快速缓解,但与TNF抑制剂相比,复发率可能更高。诊断标准和分类标准的长期缺失,以及研究终点的定义,小样本量和可变的治疗方法对研究的解释和治疗之间的比较提出了挑战。迫切需要前瞻性随机对照试验来改善证据基础,从而批准CNO的治疗。
{"title":"Treatment of pediatric chronic nonbacterial osteomyelitis - a systematic review.","authors":"Sarah Turner, Eve Roberts, Natalie Hall, Christian M Hedrich","doi":"10.1016/j.autrev.2026.104005","DOIUrl":"https://doi.org/10.1016/j.autrev.2026.104005","url":null,"abstract":"<p><p>Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease most commonly affecting children and young people. CNO can cause bone pain, hyperostosis and fractures, thereby significantly impacting on patients' wellbeing. The molecular pathophysiology of CNO is characterized by NLRP3 inflammasome activation and a pronounced imbalance between pro- and anti-inflammatory cytokines. In the absence of clinical trials, treatment of CNO remains empiric and is based on personal experience and published case series. This project systematically reviewed the available literature in pediatric CNO following 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) guidance accessing Medline, Embase, NCBI PubMed, Cochrane Library Clinical Trials, ClinicalTrials.gov, and WHO ICTRP. Nonsteroidal anti-inflammatory drugs are usually used as first-line treatment. They facilitate pain control and induce early remission in some patients but also associate with later flares. Conventional disease modifying antirheumatic drugs (DMARDs) have been used with mixed success and may be helpful in patients with associated arthritis, skin inflammation, and/or inflammatory bowel disease. Biologic DMARDs, namely TNF inhibitors, are effective for the treatment of bone and associated skin and/or bowel disease. Bisphosphonates induce rapid remission in most patients but may associate with higher relapse rates when compared to TNF inhibitors. The longstanding absence of diagnostic and, until recently, classification criteria as well as defined study endpoints, the small sample size and variable therapeutic approaches challenge interpretation of studies and comparisons between treatments. Prospective randomised controlled trials are urgently needed to improve the evidence base, resulting in approval of treatments for CNO.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"104005"},"PeriodicalIF":8.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Heavy and trace metals toxicity implications in the breakdown of cellular homeostasis: A risk factor for rheumatoid arthritis pathogenesis. 重金属和痕量金属在细胞稳态破坏中的毒性影响:类风湿关节炎发病的一个危险因素。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-05 DOI: 10.1016/j.autrev.2026.104003
Nemat Ali, Ali M Alaseem, Md Meraj Ansari, Shambhu Kumar, Mohammad Suhail Akhter, Mohammad Fareed, Prawez Alam, Glowi Alasiri

Occupational and environmental exposure to heavy and trace metals is increasingly implicated in cellular dysfunction underlying the pathogenesis of rheumatoid arthritis (RA). While trace metals such as selenium (Se), zinc (Zn), and copper (Cu) are essential for the regulation of immune and inflammatory responses, excessive or imbalanced exposure can disrupt physiological homeostasis. In contrast, exposure to heavy metals including lead (Pb), mercury (Hg), cadmium (Cd), and nickel (Ni) poses significant risks to joint health and has been increasingly associated with progressive joint tissue deterioration. Accumulating evidence indicates that metal-induced toxicity disrupts cellular homeostasis by promoting reactive oxygen species (ROS)-mediated oxidative stress and impairing key cellular processes, including apoptosis, ferroptosis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. Moreover, heavy metals may interfere with the autophagy-lysosomal pathway, a critical mechanism for maintaining cellular integrity and immune balance. This review underscores the importance of understanding the complex interactions between heavy and trace metal exposure and their roles in cellular dysfunction and joint tissue degeneration. Elucidating the molecular mechanisms underlying metal-induced toxicity is essential for the development of targeted therapeutic strategies and effective preventive interventions aimed at mitigating RA progression.

职业和环境暴露于重金属和微量金属是越来越牵连细胞功能障碍潜在的发病机制类风湿性关节炎(RA)。虽然微量金属如硒(Se)、锌(Zn)和铜(Cu)对免疫和炎症反应的调节至关重要,但过量或不平衡的暴露会破坏生理稳态。相反,暴露于重金属,包括铅(Pb)、汞(Hg)、镉(Cd)和镍(Ni)对关节健康构成重大风险,并日益与进行性关节组织恶化相关。越来越多的证据表明,金属诱导的毒性通过促进活性氧(ROS)介导的氧化应激和损害关键的细胞过程,包括凋亡、铁凋亡、线粒体功能障碍和内质网(ER)应激,破坏细胞内稳态。此外,重金属可能会干扰自噬-溶酶体途径,这是维持细胞完整性和免疫平衡的关键机制。这篇综述强调了理解重金属和微量金属暴露之间复杂的相互作用及其在细胞功能障碍和关节组织变性中的作用的重要性。阐明金属诱导毒性的分子机制对于制定靶向治疗策略和有效的预防干预措施以减轻RA的进展至关重要。
{"title":"Heavy and trace metals toxicity implications in the breakdown of cellular homeostasis: A risk factor for rheumatoid arthritis pathogenesis.","authors":"Nemat Ali, Ali M Alaseem, Md Meraj Ansari, Shambhu Kumar, Mohammad Suhail Akhter, Mohammad Fareed, Prawez Alam, Glowi Alasiri","doi":"10.1016/j.autrev.2026.104003","DOIUrl":"https://doi.org/10.1016/j.autrev.2026.104003","url":null,"abstract":"<p><p>Occupational and environmental exposure to heavy and trace metals is increasingly implicated in cellular dysfunction underlying the pathogenesis of rheumatoid arthritis (RA). While trace metals such as selenium (Se), zinc (Zn), and copper (Cu) are essential for the regulation of immune and inflammatory responses, excessive or imbalanced exposure can disrupt physiological homeostasis. In contrast, exposure to heavy metals including lead (Pb), mercury (Hg), cadmium (Cd), and nickel (Ni) poses significant risks to joint health and has been increasingly associated with progressive joint tissue deterioration. Accumulating evidence indicates that metal-induced toxicity disrupts cellular homeostasis by promoting reactive oxygen species (ROS)-mediated oxidative stress and impairing key cellular processes, including apoptosis, ferroptosis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. Moreover, heavy metals may interfere with the autophagy-lysosomal pathway, a critical mechanism for maintaining cellular integrity and immune balance. This review underscores the importance of understanding the complex interactions between heavy and trace metal exposure and their roles in cellular dysfunction and joint tissue degeneration. Elucidating the molecular mechanisms underlying metal-induced toxicity is essential for the development of targeted therapeutic strategies and effective preventive interventions aimed at mitigating RA progression.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"104003"},"PeriodicalIF":8.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sarcoidosis: Disease mechanisms, diagnostic pathway and treatment. 结节病:发病机制、诊断途径和治疗。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-04 DOI: 10.1016/j.autrev.2026.103993
Jelle Miedema, Hilario Nunes, Virgil A S H Dalm, Marc A Judson, Paolo Spagnolo

Sarcoidosis is an inflammatory granulomatous disease that affects people worldwide and can involve virtually any organ but most commonly the lungs and thoracic lymph nodes. The cause of sarcoidosis remains unknown, but occupational and environmental exposures, genetic background, and ethnicity are likely contributors to disease development. Recent immunological studies, including single-cell RNA sequencing and spatial transcriptomics, have increased our understanding of disease pathogenesis. Diagnosing sarcoidosis is often challenging due to the lack of a diagnostic gold standard and the remarkable variability in clinical presentation. Accordingly, the diagnosis requires the presence of compatible clinical and radiological features along with histopathological evidence of noncaseating granulomas and exclusion of other granulomatous diseases. The differential diagnosis includes infection, drug-induced granulomatosis, inborn error of immunity, vasculitis and malignancies. Sarcoidosis often resolves spontaneously, but it is not a benign disease. Up to one-third of patients develops chronic or progressive disease, which carries an increased risk of organ failure or death. Treatment is not always required, but is clearly indicated for progressive pulmonary disease, symptomatic cardiac or central nervous system involvement, and significantly impaired quality of life. Treatment aims to decrease symptom burden and preserve organ function. Corticosteroids have been considered first-line treatment for decades, but their long-term use is associated with substantial toxicity. Recently, methotrexate was found to be equally effective as prednisone as first-line treatment in pulmonary sarcoidosis. The identification of novel pathways involved in disease pathogenesis has suggested JAK inhibitors and mTOR inhibitors as potential therapies. More efficacious and better tolerated therapies are urgently needed; however, the rarity of the disease, its heterogeneous clinical course and the lack of prognostic biomarkers make it difficult to design and implement clinical trials of novel therapies.

结节病是一种炎症性肉芽肿性疾病,影响全世界的人,几乎可以累及任何器官,但最常见的是肺和胸淋巴结。结节病的病因尚不清楚,但职业和环境暴露、遗传背景和种族可能是疾病发展的因素。最近的免疫学研究,包括单细胞RNA测序和空间转录组学,增加了我们对疾病发病机制的理解。结节病的诊断往往是具有挑战性的,因为缺乏诊断金标准和显著的变异性在临床表现。因此,诊断需要符合临床和影像学特征以及非干酪化性肉芽肿的组织病理学证据,并排除其他肉芽肿性疾病。鉴别诊断包括感染、药物性肉芽肿、先天免疫缺陷、血管炎和恶性肿瘤。结节病常自发消退,但它不是一种良性疾病。多达三分之一的患者发展为慢性或进行性疾病,这增加了器官衰竭或死亡的风险。治疗并不总是必需的,但对于进行性肺部疾病,有症状的心脏或中枢神经系统受累,以及生活质量明显受损时,治疗是明确的。治疗的目的是减轻症状负担,保持器官功能。几十年来,皮质类固醇一直被认为是一线治疗方法,但长期使用会带来巨大的毒性。最近,甲氨蝶呤被发现在肺结节病的一线治疗中与强的松同样有效。在疾病发病机制的新途径的鉴定表明,JAK抑制剂和mTOR抑制剂是潜在的治疗方法。迫切需要更有效和耐受性更好的治疗方法;然而,这种疾病的罕见性,其异质性的临床过程和缺乏预后生物标志物使得设计和实施新疗法的临床试验变得困难。
{"title":"Sarcoidosis: Disease mechanisms, diagnostic pathway and treatment.","authors":"Jelle Miedema, Hilario Nunes, Virgil A S H Dalm, Marc A Judson, Paolo Spagnolo","doi":"10.1016/j.autrev.2026.103993","DOIUrl":"https://doi.org/10.1016/j.autrev.2026.103993","url":null,"abstract":"<p><p>Sarcoidosis is an inflammatory granulomatous disease that affects people worldwide and can involve virtually any organ but most commonly the lungs and thoracic lymph nodes. The cause of sarcoidosis remains unknown, but occupational and environmental exposures, genetic background, and ethnicity are likely contributors to disease development. Recent immunological studies, including single-cell RNA sequencing and spatial transcriptomics, have increased our understanding of disease pathogenesis. Diagnosing sarcoidosis is often challenging due to the lack of a diagnostic gold standard and the remarkable variability in clinical presentation. Accordingly, the diagnosis requires the presence of compatible clinical and radiological features along with histopathological evidence of noncaseating granulomas and exclusion of other granulomatous diseases. The differential diagnosis includes infection, drug-induced granulomatosis, inborn error of immunity, vasculitis and malignancies. Sarcoidosis often resolves spontaneously, but it is not a benign disease. Up to one-third of patients develops chronic or progressive disease, which carries an increased risk of organ failure or death. Treatment is not always required, but is clearly indicated for progressive pulmonary disease, symptomatic cardiac or central nervous system involvement, and significantly impaired quality of life. Treatment aims to decrease symptom burden and preserve organ function. Corticosteroids have been considered first-line treatment for decades, but their long-term use is associated with substantial toxicity. Recently, methotrexate was found to be equally effective as prednisone as first-line treatment in pulmonary sarcoidosis. The identification of novel pathways involved in disease pathogenesis has suggested JAK inhibitors and mTOR inhibitors as potential therapies. More efficacious and better tolerated therapies are urgently needed; however, the rarity of the disease, its heterogeneous clinical course and the lack of prognostic biomarkers make it difficult to design and implement clinical trials of novel therapies.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"103993"},"PeriodicalIF":8.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of infection for different B-cell targeting agents in treating systemic lupus erythematosus: A systematic review and network meta-analysis 不同b细胞靶向药物治疗系统性红斑狼疮的感染风险:系统综述和网络荟萃分析。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.autrev.2026.103987
Zhibin Yu , Yuxiang Lin

Objectives

This study aimed to assess the risk of infections in the treatment of systemic lupus erythematosus (SLE) with various B-cell targeting agents.

Methods

We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for randomized controlled trials (RCTs) of B-cell targeting agents for SLE as of March 1, 2025. The risk of bias was assessed using Cochrane and NIH tools. The main outcomes were total and serious infections. We performed traditional (TMA) and network meta-analyses (NMA). The risk ratios (RRs) with 95% confidence intervals (CIs) or credible intervals (CrIs) were calculated.

Results

A total of 26 studies with 16,338 patients were included, involving 12 B-cell targeting agents. Overall, B-cell targeting therapy did not significantly increase the risk of infections. Nonetheless, obinutuzumab was associated with a greater risk of infections in patients with lupus nephritis compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.37]) and rituximab (RR [95% CrI] = 1.25 [1.04, 1.53]). It was also associated with an elevated risk of infections in the combined population compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.36]), rituximab (RR [95% CrI] = 1.22 [1.04, 1.43]), and epratuzumab (RR [95% CrI] = 1.24 [1.06, 1.45]). BAFF/APRIL-targeting agents showed a higher risk of infections than anti-CD22 agents (only epratuzumab) (RR [95% CrI] = 1.16 [1.01, 1.34]). Low-dose therapy also showed a notably increased risk compared to placebo (RR [95% CrI] = 1.05 [1.00, 1.10]). No significant increase in the risk of serious infections was found.

Conclusions

Specific B-cell targeting therapies may modestly increase the risk of total infections.
目的:本研究旨在评估不同b细胞靶向药物治疗系统性红斑狼疮(SLE)的感染风险。方法:系统检索PubMed、Web of Science、Cochrane Library和Embase,检索截至2025年3月1日的SLE b细胞靶向药物的随机对照试验(rct)。使用Cochrane和NIH工具评估偏倚风险。主要结局为总感染和严重感染。我们进行了传统(TMA)和网络元分析(NMA)。计算具有95%置信区间(CIs)或可信区间(CrIs)的风险比(rr)。结果:共纳入26项研究,16,338例患者,涉及12种b细胞靶向药物。总的来说,b细胞靶向治疗并没有显著增加感染的风险。尽管如此,与安慰剂相比,obinutuzumab与狼疮性肾炎的风险更高(RR [95% CrI] = 1.18[1.03,1.37])和利妥昔单抗(RR [95% CrI] = 1.25[1.04,1.53])。与安慰剂(RR [95% CrI] = 1.18[1.03,1.36])、利妥昔单抗(RR [95% CrI] = 1.22[1.04,1.43])和依普妥珠单抗(RR [95% CrI] = 1.24[1.06,1.45])相比,该药还与联合人群感染风险升高相关。BAFF/ april靶向药物的感染风险高于抗cd22药物(仅为epratuzumab) (RR [95% CrI] = 1.16[1.01,1.34])。与安慰剂相比,低剂量治疗也显着增加了风险(RR [95% CrI] = 1.05[1.00,1.10])。没有发现严重感染的风险显著增加。结论:特异性b细胞靶向治疗可能会适度增加总感染的风险。
{"title":"Risk of infection for different B-cell targeting agents in treating systemic lupus erythematosus: A systematic review and network meta-analysis","authors":"Zhibin Yu ,&nbsp;Yuxiang Lin","doi":"10.1016/j.autrev.2026.103987","DOIUrl":"10.1016/j.autrev.2026.103987","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to assess the risk of infections in the treatment of systemic lupus erythematosus (SLE) with various B-cell targeting agents.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for randomized controlled trials (RCTs) of B-cell targeting agents for SLE as of March 1, 2025. The risk of bias was assessed using Cochrane and NIH tools. The main outcomes were total and serious infections. We performed traditional (TMA) and network meta-analyses (NMA). The risk ratios (RRs) with 95% confidence intervals (CIs) or credible intervals (CrIs) were calculated.</div></div><div><h3>Results</h3><div>A total of 26 studies with 16,338 patients were included, involving 12 B-cell targeting agents. Overall, B-cell targeting therapy did not significantly increase the risk of infections. Nonetheless, obinutuzumab was associated with a greater risk of infections in patients with lupus nephritis compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.37]) and rituximab (RR [95% CrI] = 1.25 [1.04, 1.53]). It was also associated with an elevated risk of infections in the combined population compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.36]), rituximab (RR [95% CrI] = 1.22 [1.04, 1.43]), and epratuzumab (RR [95% CrI] = 1.24 [1.06, 1.45]). BAFF/APRIL-targeting agents showed a higher risk of infections than anti-CD22 agents (only epratuzumab) (RR [95% CrI] = 1.16 [1.01, 1.34]). Low-dose therapy also showed a notably increased risk compared to placebo (RR [95% CrI] = 1.05 [1.00, 1.10]). No significant increase in the risk of serious infections was found.</div></div><div><h3>Conclusions</h3><div>Specific B-cell targeting therapies may modestly increase the risk of total infections.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103987"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent advances in the mechanisms and treatment of cuproptosis in autoimmune diseases 自身免疫性疾病中铜凸的机制及治疗的最新进展。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.autrev.2026.103994
Yan Liu , Xiyuan Bao , Xin Dai , Xue Liu , Danni Zhu , Jiejie Qiao , Haifeng Pan , Jing Wang
Autoimmune diseases, characterized by the immune system's erroneous attack on the body's own tissues, are highly challenging to treat. Recently discovered cuproptosis, triggered by excess copper ions, leads to the abnormal accumulation of acetylated proteins and mitochondrial dysfunction, and has become a research hotspot in this field. Recent studies have shown that cuproptosis-related genes (CRGs) play a potential role in various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Primary Sjögren's syndrome (pSS), and ankylosing spondylitis (AS), and hold promise for diagnosis and regulation. This article systematically reviews the latest progress of cuproptosis in autoimmune diseases, explores the potential of CRGs as diagnostic biomarkers and immune modulators, evaluates the therapeutic potential of targeting CRGs, and looks forward to how nanotechnology can revolutionize treatment strategies. By elucidating the mechanisms of cuproptosis in autoimmune diseases, this article aims to pave new paths for future research and lay the foundation for innovative therapies.
自身免疫性疾病的特点是免疫系统对人体自身组织的错误攻击,治疗起来极具挑战性。近年来发现的由过量铜离子引发的乙酰化蛋白异常积累和线粒体功能障碍导致的cuprotosis已成为该领域的研究热点。最近的研究表明,铜裂相关基因(CRGs)在各种自身免疫性疾病中发挥潜在作用,如系统性红斑狼疮(SLE)、类风湿性关节炎(RA)、原发性Sjögren综合征(pSS)和强直性脊柱炎(as),并有望用于诊断和调节。本文系统综述了自身免疫性疾病中铜突的最新进展,探讨了CRGs作为诊断性生物标志物和免疫调节剂的潜力,评估了靶向CRGs的治疗潜力,并展望了纳米技术如何改变治疗策略。本文旨在通过阐明自身免疫性疾病中铜质增生的机制,为未来的研究开辟新的途径,为创新疗法奠定基础。
{"title":"Recent advances in the mechanisms and treatment of cuproptosis in autoimmune diseases","authors":"Yan Liu ,&nbsp;Xiyuan Bao ,&nbsp;Xin Dai ,&nbsp;Xue Liu ,&nbsp;Danni Zhu ,&nbsp;Jiejie Qiao ,&nbsp;Haifeng Pan ,&nbsp;Jing Wang","doi":"10.1016/j.autrev.2026.103994","DOIUrl":"10.1016/j.autrev.2026.103994","url":null,"abstract":"<div><div>Autoimmune diseases, characterized by the immune system's erroneous attack on the body's own tissues, are highly challenging to treat. Recently discovered cuproptosis, triggered by excess copper ions, leads to the abnormal accumulation of acetylated proteins and mitochondrial dysfunction, and has become a research hotspot in this field. Recent studies have shown that cuproptosis-related genes (CRGs) play a potential role in various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Primary Sjögren's syndrome (pSS), and ankylosing spondylitis (AS), and hold promise for diagnosis and regulation. This article systematically reviews the latest progress of cuproptosis in autoimmune diseases, explores the potential of CRGs as diagnostic biomarkers and immune modulators, evaluates the therapeutic potential of targeting CRGs, and looks forward to how nanotechnology can revolutionize treatment strategies. By elucidating the mechanisms of cuproptosis in autoimmune diseases, this article aims to pave new paths for future research and lay the foundation for innovative therapies.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103994"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sporadic late-onset nemaline myopathy (SLONM): Data from a case series and literature review of 144 patients. 散发性迟发性线状肌病(SLONM):来自144例患者的病例系列和文献综述的数据。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-19 DOI: 10.1016/j.autrev.2025.103960
Antonio Lauletta, Francesca Forcina, Gioia Merlonghi, Laura Fionda, Luca Leonardi, Rocco Costanzo, Laura Tufano, Elena Rossini, Demetrio Marando, Valentina Vera, Giovanni Antonini, Stefania Morino, Matteo Garibaldi

Sporadic Late-Onset Nemaline Myopathy (SLONM) is an acquired myopathy presenting in adulthood with progressive proximal and axial muscle weakness. A substantial proportion of cases are associated with monoclonal gammopathy of undetermined significance (MGUS), referred to as SLONM-MGUS, suggesting a potential immune-mediated pathogenesis. Although the presence of MGUS has clinical and therapeutic implications, its exact role in disease severity and progression remains unclear. We aimed to characterize clinical, pathological, and prognostic differences between SLONM-MGUS and SLONM without MGUS (SLONM-noMGUS). We conducted a systematic review of SLONM case series published over the past 25 years, supplemented by a single-center case series of five additional patients from our institution (Sant'Andrea Hospital, Rome). Eligible subjects included adult patients diagnosed with SLONM based on clinical features and muscle biopsy demonstrating nemaline rods. Data on demographics, laboratory parameters, histopathological findings, treatments and outcomes were extracted and compared between SLONM-MGUS and SLONM-noMGUS cohorts. Of the 144 patients analyzed, 47 % were classified as SLONM-MGUS. These patients exhibited more severe clinical manifestations, including increased respiratory involvement (p = 0.006). Histopathologically, SLONM-MGUS revealed more prominent nemaline rods (p = 0.032), often accompanied by cytoplasmic bodies and lobulated fibers, and frequently required repeat muscle biopsies for diagnosis (p = 0.0285). Inflammatory infiltrates were less frequent in SLONM-MGUS (p = 0.0176). Functional outcomes were significantly worse in this group, with reduced likelihood of full recovery (p = 0.013) and higher rates of non-ambulatory status (p = 0.01). Patients receiving dual or more treatment regimens, particularly those including IVIg and/or autologous stem cell transplantation (ASCT), had more favorable outcomes. These findings indicate that SLONM-MGUS represents a more severe phenotype of SLONM with distinct clinico-pathological features and poorer prognosis. Notably, combined treatment regimens, including IVIg and/or ASCT, were associated with improved outcomes, highlighting the importance of early recognition and aggressive therapeutic strategies in selected patients.

散发性迟发性线状肌病(SLONM)是一种后天性肌病,表现为成年期进行性近端和轴向肌无力。相当大比例的病例与未确定意义的单克隆γ病(MGUS)相关,称为SLONM-MGUS,提示潜在的免疫介导发病机制。尽管MGUS的存在具有临床和治疗意义,但其在疾病严重程度和进展中的确切作用尚不清楚。我们的目的是表征SLONM-MGUS和无MGUS的SLONM (SLONM- nomgus)之间的临床、病理和预后差异。我们对过去25 年发表的SLONM病例系列进行了系统回顾,并辅以我们机构(罗马圣安德里亚医院)另外5名患者的单中心病例系列。符合条件的受试者包括根据临床特征和肌肉活检显示线状棒诊断为SLONM的成年患者。提取SLONM-MGUS和SLONM-noMGUS队列的人口统计学、实验室参数、组织病理学结果、治疗和结果数据并进行比较。在分析的144例患者中,47% %被归类为SLONM-MGUS。这些患者表现出更严重的临床表现,包括呼吸受累加重(p = 0.006)。组织病理学上,SLONM-MGUS显示更突出的线状棒(p = 0.032),常伴有细胞质体和分叶纤维,经常需要重复肌肉活检诊断(p = 0.0285)。SLONM-MGUS中炎症浸润较少(p = 0.0176)。该组的功能结果明显较差,完全恢复的可能性降低(p = 0.013),非活动状态的发生率较高(p = 0.01)。接受双重或更多治疗方案的患者,特别是那些包括IVIg和/或自体干细胞移植(ASCT)的患者,有更有利的结果。这些结果表明,SLONM- mgus是一种更严重的SLONM表型,具有明显的临床病理特征和较差的预后。值得注意的是,联合治疗方案,包括IVIg和/或ASCT,与改善的结果相关,突出了早期识别和积极治疗策略在选定患者中的重要性。
{"title":"Sporadic late-onset nemaline myopathy (SLONM): Data from a case series and literature review of 144 patients.","authors":"Antonio Lauletta, Francesca Forcina, Gioia Merlonghi, Laura Fionda, Luca Leonardi, Rocco Costanzo, Laura Tufano, Elena Rossini, Demetrio Marando, Valentina Vera, Giovanni Antonini, Stefania Morino, Matteo Garibaldi","doi":"10.1016/j.autrev.2025.103960","DOIUrl":"10.1016/j.autrev.2025.103960","url":null,"abstract":"<p><p>Sporadic Late-Onset Nemaline Myopathy (SLONM) is an acquired myopathy presenting in adulthood with progressive proximal and axial muscle weakness. A substantial proportion of cases are associated with monoclonal gammopathy of undetermined significance (MGUS), referred to as SLONM-MGUS, suggesting a potential immune-mediated pathogenesis. Although the presence of MGUS has clinical and therapeutic implications, its exact role in disease severity and progression remains unclear. We aimed to characterize clinical, pathological, and prognostic differences between SLONM-MGUS and SLONM without MGUS (SLONM-noMGUS). We conducted a systematic review of SLONM case series published over the past 25 years, supplemented by a single-center case series of five additional patients from our institution (Sant'Andrea Hospital, Rome). Eligible subjects included adult patients diagnosed with SLONM based on clinical features and muscle biopsy demonstrating nemaline rods. Data on demographics, laboratory parameters, histopathological findings, treatments and outcomes were extracted and compared between SLONM-MGUS and SLONM-noMGUS cohorts. Of the 144 patients analyzed, 47 % were classified as SLONM-MGUS. These patients exhibited more severe clinical manifestations, including increased respiratory involvement (p = 0.006). Histopathologically, SLONM-MGUS revealed more prominent nemaline rods (p = 0.032), often accompanied by cytoplasmic bodies and lobulated fibers, and frequently required repeat muscle biopsies for diagnosis (p = 0.0285). Inflammatory infiltrates were less frequent in SLONM-MGUS (p = 0.0176). Functional outcomes were significantly worse in this group, with reduced likelihood of full recovery (p = 0.013) and higher rates of non-ambulatory status (p = 0.01). Patients receiving dual or more treatment regimens, particularly those including IVIg and/or autologous stem cell transplantation (ASCT), had more favorable outcomes. These findings indicate that SLONM-MGUS represents a more severe phenotype of SLONM with distinct clinico-pathological features and poorer prognosis. Notably, combined treatment regimens, including IVIg and/or ASCT, were associated with improved outcomes, highlighting the importance of early recognition and aggressive therapeutic strategies in selected patients.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"103960"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FcγRIIa in autoimmunity: Unraveling pathogenic mechanisms and therapeutic opportunities. 自身免疫中的FcγRIIa:揭示致病机制和治疗机会。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-12-08 DOI: 10.1016/j.autrev.2025.103974
Bo Zhu, Xinhua Cao, Xue Wang, Luyao Yu, Wenhao Zhou, Lihua Zhu, Qingling Yang, Ke Rui

Autoantibodies, hallmark mediators of autoimmune diseases, drive pathogenesis through Fc receptors (FcRs) engagement. Among human FcRs, FcγRIIa is the most abundantly expressed subtype and plays a pivotal role in regulating both innate and adaptive immune responses. Genetic polymorphisms and dysregulated FcγRIIa signaling are increasingly implicated in autoimmune pathogenesis. By governing immune cell activation, differentiation, and effector functions, FcγRIIa emerges as a central orchestrator of immune responses. Recent clinical studies have identified FcγRIIa as a promising therapeutic target in patients with autoimmune diseases, as well as in murine autoimmune models. This review outlines the structure and cellular expression profile of FcγRIIa and elucidates its role in immune regulation. Furthermore, we discuss its association with autoimmune pathogenesis and highlight FcγRIIa targeted therapeutics evaluated in past and ongoing clinical trials for autoimmune disease treatment.

自身抗体是自身免疫性疾病的标志性介质,通过Fc受体(FcRs)参与驱动发病机制。在人类fcr中,FcγRIIa是表达最丰富的亚型,在调节先天和适应性免疫反应中起关键作用。遗传多态性和失调的FcγRIIa信号越来越多地与自身免疫发病机制有关。通过控制免疫细胞的激活、分化和效应功能,FcγRIIa成为免疫反应的中心协调者。最近的临床研究已经确定FcγRIIa在自身免疫性疾病患者以及小鼠自身免疫性模型中是一种有希望的治疗靶点。本文综述了fc γ - riia的结构和细胞表达谱,并阐明了其在免疫调节中的作用。此外,我们讨论了其与自身免疫性发病机制的关联,并强调了在过去和正在进行的自身免疫性疾病治疗临床试验中评估的FcγRIIa靶向治疗方法。
{"title":"FcγRIIa in autoimmunity: Unraveling pathogenic mechanisms and therapeutic opportunities.","authors":"Bo Zhu, Xinhua Cao, Xue Wang, Luyao Yu, Wenhao Zhou, Lihua Zhu, Qingling Yang, Ke Rui","doi":"10.1016/j.autrev.2025.103974","DOIUrl":"10.1016/j.autrev.2025.103974","url":null,"abstract":"<p><p>Autoantibodies, hallmark mediators of autoimmune diseases, drive pathogenesis through Fc receptors (FcRs) engagement. Among human FcRs, FcγRIIa is the most abundantly expressed subtype and plays a pivotal role in regulating both innate and adaptive immune responses. Genetic polymorphisms and dysregulated FcγRIIa signaling are increasingly implicated in autoimmune pathogenesis. By governing immune cell activation, differentiation, and effector functions, FcγRIIa emerges as a central orchestrator of immune responses. Recent clinical studies have identified FcγRIIa as a promising therapeutic target in patients with autoimmune diseases, as well as in murine autoimmune models. This review outlines the structure and cellular expression profile of FcγRIIa and elucidates its role in immune regulation. Furthermore, we discuss its association with autoimmune pathogenesis and highlight FcγRIIa targeted therapeutics evaluated in past and ongoing clinical trials for autoimmune disease treatment.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"103974"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Autoantibody internalization in myositis skeletal muscle: Emerging evidence, mechanistic insights, and therapeutic relevance. 骨骼肌炎的自身抗体内化:新出现的证据、机制见解和治疗相关性。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-25 DOI: 10.1016/j.autrev.2025.103962
Raphael A Kirou, Iago Pinal-Fernandez, Andrew L Mammen

The inflammatory myopathies-including dermatomyositis, immune-mediated necrotizing myopathy, anti-synthetase syndrome, and overlap myositis-are systemic autoimmune diseases characterized by myositis-specific and myositis-associated autoantibodies targeting intracellular antigens. These diseases can be subclassified by autoantibody seropositivity, based on the understanding that each myositis autoantibody is associated with distinct clinical features. Traditionally, given the intracellular nature of their targets, myositis autoantibodies were thought to be non-pathogenic. However, this idea is now being challenged based on data from recent and older studies showing that autoantibodies reach their intracellular targets in vivo and exert functional pathogenic effects. In this review, we summarize experimental evidence supporting a model of pathogenic autoantibody internalization in the skeletal muscle of different inflammatory myopathies. We also address gaps in the evidence for this model, including the lack of a proven mechanism of autoantibody entry, while offering suggestions for future studies to fill these gaps. We discuss possible mechanisms of autoantibody entry, as well as the diagnostic, prognostic, and therapeutic implications of this model. Finally, we propose that autoantibodies targeting intracellular antigens in other autoimmune diseases-including certain autoimmune neurologic disorders, systemic sclerosis, systemic lupus erythematosus, and vasculitis-could potentially play a role in these conditions.

炎性肌病——包括皮肌炎、免疫介导的坏死性肌病、抗合成酶综合征和重叠性肌炎——是一种系统性自身免疫性疾病,其特征是肌炎特异性和肌炎相关的自身抗体靶向细胞内抗原。基于每种肌炎自身抗体与不同的临床特征相关的认识,这些疾病可根据自身抗体血清阳性再分类。传统上,鉴于其靶点的细胞内性质,肌炎自身抗体被认为是非致病性的。然而,这一观点现在正受到挑战,因为最近和以前的研究数据表明,自身抗体在体内到达细胞内靶点并发挥功能性致病作用。在这篇综述中,我们总结了支持不同炎性肌病骨骼肌病原性自身抗体内化模型的实验证据。我们还解决了该模型证据中的空白,包括缺乏经过验证的自身抗体进入机制,同时为未来的研究提供了填补这些空白的建议。我们讨论了自身抗体进入的可能机制,以及该模型的诊断、预后和治疗意义。最后,我们提出针对其他自身免疫性疾病(包括某些自身免疫性神经系统疾病、系统性硬化症、系统性红斑狼疮和血管炎)的细胞内抗原的自身抗体可能在这些疾病中发挥作用。
{"title":"Autoantibody internalization in myositis skeletal muscle: Emerging evidence, mechanistic insights, and therapeutic relevance.","authors":"Raphael A Kirou, Iago Pinal-Fernandez, Andrew L Mammen","doi":"10.1016/j.autrev.2025.103962","DOIUrl":"10.1016/j.autrev.2025.103962","url":null,"abstract":"<p><p>The inflammatory myopathies-including dermatomyositis, immune-mediated necrotizing myopathy, anti-synthetase syndrome, and overlap myositis-are systemic autoimmune diseases characterized by myositis-specific and myositis-associated autoantibodies targeting intracellular antigens. These diseases can be subclassified by autoantibody seropositivity, based on the understanding that each myositis autoantibody is associated with distinct clinical features. Traditionally, given the intracellular nature of their targets, myositis autoantibodies were thought to be non-pathogenic. However, this idea is now being challenged based on data from recent and older studies showing that autoantibodies reach their intracellular targets in vivo and exert functional pathogenic effects. In this review, we summarize experimental evidence supporting a model of pathogenic autoantibody internalization in the skeletal muscle of different inflammatory myopathies. We also address gaps in the evidence for this model, including the lack of a proven mechanism of autoantibody entry, while offering suggestions for future studies to fill these gaps. We discuss possible mechanisms of autoantibody entry, as well as the diagnostic, prognostic, and therapeutic implications of this model. Finally, we propose that autoantibodies targeting intracellular antigens in other autoimmune diseases-including certain autoimmune neurologic disorders, systemic sclerosis, systemic lupus erythematosus, and vasculitis-could potentially play a role in these conditions.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"103962"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting age-related cell-free DNA for prevention, early diagnosis and treatment of rheumatoid arthritis. 靶向年龄相关的无细胞DNA用于类风湿关节炎的预防、早期诊断和治疗。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-29 DOI: 10.1016/j.autrev.2025.103961
Ning Ma, Yulin Xu, Dingqi Zhang, Huan-Tian Zhang, Weidan Luo, Yang Cao, Vincent Kam Wai Wong

Cell-free DNA (cf-DNA) refers to extracellular DNA fragments released during cell death, which have been observed to accumulate with advancing age. Elevated cf-DNA concentrations have been detected in the plasma and disease-affected tissues of patients with multiple disorders, particularly age-related autoimmune diseases such as rheumatoid arthritis (RA). Growing evidence supports the potential of cf-DNA as a biomarker for a broad spectrum of autoimmune and age-associated conditions, including cancer, systemic lupus erythematosus (SLE), and psoriasis. Fluctuations in cf-DNA levels and characteristics appear to be closely associated with disease onset, progression, severity, and prognosis. Importantly, emerging studies indicate that cf-DNA may not merely act as a passive biomarker but could also function as an active mediator contributing to RA pathogenesis through distinct immunological pathways. These insights suggest that cf-DNA represents a promising target for the development of innovative diagnostic, preventive, and therapeutic strategies. In this review, we summarize the current understanding of age-related cf-DNA in RA, highlight its potential immunopathological roles, and discuss recent advances in cf-DNA-based diagnostic tools, preventive approaches, and therapeutic interventions with possible clinical translational value.

游离细胞DNA (cf-DNA)是指细胞死亡过程中释放的细胞外DNA片段,它们随着年龄的增长而积累。在患有多种疾病,特别是与年龄相关的自身免疫性疾病(如类风湿性关节炎)的患者的血浆和疾病影响组织中检测到升高的cf-DNA浓度。越来越多的证据支持cf-DNA作为广泛的自身免疫和年龄相关疾病的生物标志物的潜力,包括癌症、系统性红斑狼疮(SLE)和牛皮癣。cf-DNA水平和特征的波动似乎与疾病的发病、进展、严重程度和预后密切相关。重要的是,新出现的研究表明,cf-DNA可能不仅仅作为一种被动的生物标志物,还可以作为一种主动的介质,通过不同的免疫途径参与RA的发病机制。这些见解表明,cf-DNA代表了创新诊断、预防和治疗策略发展的一个有希望的目标。在这篇综述中,我们总结了目前对RA中年龄相关的cf-DNA的理解,强调了其潜在的免疫病理作用,并讨论了基于cf-DNA的诊断工具,预防方法和治疗干预的最新进展,可能具有临床转化价值。
{"title":"Targeting age-related cell-free DNA for prevention, early diagnosis and treatment of rheumatoid arthritis.","authors":"Ning Ma, Yulin Xu, Dingqi Zhang, Huan-Tian Zhang, Weidan Luo, Yang Cao, Vincent Kam Wai Wong","doi":"10.1016/j.autrev.2025.103961","DOIUrl":"10.1016/j.autrev.2025.103961","url":null,"abstract":"<p><p>Cell-free DNA (cf-DNA) refers to extracellular DNA fragments released during cell death, which have been observed to accumulate with advancing age. Elevated cf-DNA concentrations have been detected in the plasma and disease-affected tissues of patients with multiple disorders, particularly age-related autoimmune diseases such as rheumatoid arthritis (RA). Growing evidence supports the potential of cf-DNA as a biomarker for a broad spectrum of autoimmune and age-associated conditions, including cancer, systemic lupus erythematosus (SLE), and psoriasis. Fluctuations in cf-DNA levels and characteristics appear to be closely associated with disease onset, progression, severity, and prognosis. Importantly, emerging studies indicate that cf-DNA may not merely act as a passive biomarker but could also function as an active mediator contributing to RA pathogenesis through distinct immunological pathways. These insights suggest that cf-DNA represents a promising target for the development of innovative diagnostic, preventive, and therapeutic strategies. In this review, we summarize the current understanding of age-related cf-DNA in RA, highlight its potential immunopathological roles, and discuss recent advances in cf-DNA-based diagnostic tools, preventive approaches, and therapeutic interventions with possible clinical translational value.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"103961"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular vesicles in autoimmune diseases: Mechanistic underpinnings and precision medicine applications. 自身免疫性疾病中的细胞外囊泡:机制基础和精准医学应用。
IF 8.3 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-21 DOI: 10.1016/j.autrev.2025.103959
Wenhui Mo, Yujie Zhang, Yu Zeng, Yanyi Zheng, Shenglan Zhao, Xiaoze Wang, Xiaoli Fan

Autoimmune diseases constitute a collection of complex disorders characterized by abnormal immune responses directed against self-tissues. The pathogenesis of these diseases is strongly linked to the interaction of genetic predispositions and environmental influences. Clinically, autoimmune diseases present with heterogeneous manifestations, and their prevalence has been steadily rising, resulting in profound impacts on patients' physical and psychological health and creating a growing challenge for healthcare infrastructures. At present, nonspecific immunosuppressants are the main treatment method, but this method has limitations such as extensive immunosuppression and serious adverse reactions. Therefore, there is an urgent need to develop novel and targeted therapeutic strategies. As crucial mediators of intercellular communication, extracellular vesicles (EVs) have become significant actors in the control of inflammatory and immunological responses, showing great promise in both mechanistic studies and clinical applications. This study offers a comprehensive overview of current developments in EV research for the main autoimmune conditions, including inflammatory bowel disease, systemic lupus erythematosus, and rheumatoid arthritis. It further comprehensively discusses the potential clinical value of EVs from the perspectives of disease pathogenesis and biomarker development, aiming to offer theoretical support and innovative directions for the clinical application of EV-based diagnostics and treatments, as well as for the realization of precision medicine in autoimmune disorders.

自身免疫性疾病是一种以针对自身组织的异常免疫反应为特征的复杂疾病的集合。这些疾病的发病机制与遗传倾向和环境影响的相互作用密切相关。在临床上,自身免疫性疾病表现各异,发病率稳步上升,对患者身心健康产生深远影响,对医疗卫生基础设施构成越来越大的挑战。目前,非特异性免疫抑制剂是主要的治疗方法,但这种方法存在广泛的免疫抑制和严重的不良反应等局限性。因此,迫切需要开发新的靶向治疗策略。作为细胞间通讯的重要介质,细胞外囊泡(EVs)已成为控制炎症和免疫反应的重要角色,在机制研究和临床应用中都显示出巨大的前景。本研究全面概述了目前EV在主要自身免疫性疾病(包括炎症性肠病、系统性红斑狼疮和类风湿性关节炎)中的研究进展。进一步从疾病发病机制和生物标志物开发等方面全面探讨ev潜在的临床价值,旨在为基于ev的诊断和治疗的临床应用,实现自身免疫性疾病的精准医疗提供理论支持和创新方向。
{"title":"Extracellular vesicles in autoimmune diseases: Mechanistic underpinnings and precision medicine applications.","authors":"Wenhui Mo, Yujie Zhang, Yu Zeng, Yanyi Zheng, Shenglan Zhao, Xiaoze Wang, Xiaoli Fan","doi":"10.1016/j.autrev.2025.103959","DOIUrl":"10.1016/j.autrev.2025.103959","url":null,"abstract":"<p><p>Autoimmune diseases constitute a collection of complex disorders characterized by abnormal immune responses directed against self-tissues. The pathogenesis of these diseases is strongly linked to the interaction of genetic predispositions and environmental influences. Clinically, autoimmune diseases present with heterogeneous manifestations, and their prevalence has been steadily rising, resulting in profound impacts on patients' physical and psychological health and creating a growing challenge for healthcare infrastructures. At present, nonspecific immunosuppressants are the main treatment method, but this method has limitations such as extensive immunosuppression and serious adverse reactions. Therefore, there is an urgent need to develop novel and targeted therapeutic strategies. As crucial mediators of intercellular communication, extracellular vesicles (EVs) have become significant actors in the control of inflammatory and immunological responses, showing great promise in both mechanistic studies and clinical applications. This study offers a comprehensive overview of current developments in EV research for the main autoimmune conditions, including inflammatory bowel disease, systemic lupus erythematosus, and rheumatoid arthritis. It further comprehensively discusses the potential clinical value of EVs from the perspectives of disease pathogenesis and biomarker development, aiming to offer theoretical support and innovative directions for the clinical application of EV-based diagnostics and treatments, as well as for the realization of precision medicine in autoimmune disorders.</p>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":" ","pages":"103959"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Autoimmunity reviews
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1