Autoimmunity reviews最新文献_第5页

The effect of Sphingosine-1-phosphate receptor modulator treatment on leukocyte subsets across different clinical indications: A systematic review 鞘氨醇-1-磷酸受体调节剂治疗对不同临床适应症白细胞亚群的影响：一项系统综述。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-09-10 DOI: 10.1016/j.autrev.2025.103934

Dimitrios Nikolakis , Christoph Teichert , Joep Grootjans , Marleen G.H. van de Sande , Geert R. D’Haens

Background

Sphingosine-1-phosphate receptor (S1PR) modulators are approved as a treatment for several autoimmune diseases. While their role on total leukocyte populations is well-studied, their effects on specific leukocyte subsets remain unclear. This systematic review describes the impact of various S1PR modulators on human leukocyte subpopulations.

Methods

We conducted a systematic literature search through the databases PubMed, Medline, Embase, and Cochrane, up to the 25th of July 2024. Studies were included if they involved patients treated with S1PR modulators and provided data on leukocyte subsets. Among the exclusion criteria, were non-English articles, animal studies, and in vitro studies. Data extraction focused on changes in leukocyte subsets post-treatment.

Results

Out of 1658 articles identified, 63 met the inclusion criteria. Fingolimod was the most frequently studied agent and displayed significant reductions in total T-cell counts. More specifically, CD4+ T-cells, including naïve and central memory populations were reduced. CD8+ T-cells also decreased, although the alterations of effector memory subsets were inconsistent. B-lymphocytes were generally attenuated. Innate immune cells showed variable responses, with most studies indicating a reduction or no change. Data on other S1PR modulators suggested similar trends.

Conclusion

S1PR modulators primarily reduce T- and B-cell subpopulations, which are known to play a prominent role in immune-mediated inflammatory disorders. Further research is needed to fully elucidate the differential effects among drugs targeting specific isoforms of the S1PR, focusing on the lymph nodes or inflammatory tissue sites (e.g. intestinal mucosa and cerebrospinal fluid), to explore the exact clinical implications of these pharmacodynamic findings.

背景：鞘氨醇-1-磷酸受体（S1PR）调节剂已被批准用于治疗多种自身免疫性疾病。虽然它们对总白细胞群的作用已被充分研究，但它们对特定白细胞亚群的影响仍不清楚。这篇系统综述描述了各种S1PR调节剂对人类白细胞亚群的影响。方法：通过PubMed、Medline、Embase和Cochrane数据库进行系统的文献检索，检索时间截止到2024年7月25日。如果研究涉及接受S1PR调节剂治疗的患者并提供白细胞亚群数据，则纳入研究。排除标准包括非英文文章、动物研究和体外研究。数据提取的重点是治疗后白细胞亚群的变化。结果：1658篇文献中，63篇符合纳入标准。芬戈莫德是最常被研究的药物，并显示出总t细胞计数的显著减少。更具体地说，CD4+ t细胞，包括naïve和中枢记忆群减少。CD8+ t细胞也减少，尽管效应记忆亚群的改变不一致。b淋巴细胞普遍减弱。先天免疫细胞表现出不同的反应，大多数研究表明减少或没有变化。其他S1PR调制器的数据也显示了类似的趋势。结论：S1PR调节剂主要减少T细胞和b细胞亚群，这两种细胞在免疫介导的炎症疾病中起着重要作用。需要进一步的研究来充分阐明针对S1PR特定亚型的药物之间的差异效应，重点是淋巴结或炎症组织部位（如肠粘膜和脑脊液），以探索这些药效学发现的确切临床意义。

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引用次数: 0

Exploring therapeutic potential of Cannabis based therapy in autoimmune and rheumatic disorders 探索大麻治疗自身免疫性疾病和风湿病的治疗潜力。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-09-02 DOI: 10.1016/j.autrev.2025.103925

Inbar Michaeli , Simon Lassman , Gilad Halpert , Giris Jacob , Howard Amital

The medical use of cannabis is expanding across many countries, with some legalizing its use outright and others implementing medical licensure systems to approve treatment for eligible patients.

Despite this growing interest and utilization, there remains a lack of solid scientific evidence supporting its medical use, even though cannabis has been used therapeutically for thousands of years.

The goal of the following communication is to present updated data on the potential roles of cannabis-based treatments in various autoimmune and rheumatic conditions. The information highlights that incorporating cannabis into the therapeutic armamentarium may offer benefits. However, in many cases, despite encouraging perspectives and outcomes, the supporting evidence remains insufficient and requires further validation.

Due to social and legal barriers, the conduct of such rigorous clinical trials has been hindered, limiting the availability of high-quality evidence to guide medical practice.

大麻的医疗用途正在许多国家扩大，一些国家将其使用完全合法化，另一些国家实施医疗执照制度，批准对符合条件的患者进行治疗。尽管人们对大麻的兴趣和利用日益增加，但尽管大麻用于治疗已有数千年的历史，但仍然缺乏支持其医疗用途的可靠科学证据。以下通讯的目的是提供关于大麻治疗在各种自身免疫性和风湿病中的潜在作用的最新数据。该信息强调，将大麻纳入治疗手段可能会带来好处。然而，在许多情况下，尽管观点和结果令人鼓舞，但支持性证据仍然不足，需要进一步验证。由于社会和法律障碍，这种严格的临床试验的进行受到阻碍，限制了指导医疗实践的高质量证据的获得。

引用次数: 0

Calcium signaling dysregulation in rheumatoid arthritis: a comparative perspective with osteoarthritis 类风湿关节炎中的钙信号失调：与骨关节炎的比较

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-28 DOI: 10.1016/j.autrev.2025.103923

Thuy Duong Nguyen , Hugo Abreu , Nicoletta Tommasi , Luigi Azzarone , Rita Maria Concetta Di Martino , Beatrice Riva , Davide Raineri , Tracey Pirali , Annalisa Chiocchetti , Giuseppe Cappellano

Rheumatoid arthritis and osteoarthritis are among the most prevalent chronic diseases worldwide, imposing a significant burden on both patients and healthcare systems. Despite their distinct etiology and progression, emerging evidence suggests that calcium signaling plays a pivotal role in the pathogenesis of both diseases by influencing a variety of cellular processes within joint tissues. Calcium is essential for regulating key cellular functions, including gene expression, muscle contraction, cell cycle progression, proliferation, apoptosis, excitation-contraction coupling, synaptic transmission, and embryonic development. Particularly, in the context of arthritic diseases, an imbalance in calcium homeostasis has significant consequences, since the osteogenic and chondrogenic processes, as well as extracellular matrix formation, are highly influenced by calcium levels. Given these insights, a deeper understanding of the mechanisms governing calcium uptake, release, and metabolism could enhance our comprehension of disease pathogenesis and facilitate the development of novel therapeutic strategies. This review provides an overview of calcium signaling mechanisms, particularly in the most affected cells and tissues in rheumatoid arthritis and osteoarthritis, and summarizes the emerging therapies targeting calcium metabolism that may improve current treatment options.

类风湿关节炎和骨关节炎是世界范围内最普遍的慢性疾病，对患者和卫生保健系统都造成了重大负担。尽管它们的病因和进展不同，但新出现的证据表明，钙信号通过影响关节组织内的多种细胞过程，在这两种疾病的发病机制中起着关键作用。钙对调节关键细胞功能至关重要，包括基因表达、肌肉收缩、细胞周期进展、增殖、凋亡、兴奋-收缩耦合、突触传递和胚胎发育。特别是，在关节炎疾病的情况下，钙稳态失衡会产生严重后果，因为成骨和软骨形成过程以及细胞外基质的形成受到钙水平的高度影响。鉴于这些见解，对钙摄取、释放和代谢机制的更深入了解可以增强我们对疾病发病机制的理解，并促进新的治疗策略的发展。本文综述了钙信号传导机制，特别是在类风湿性关节炎和骨关节炎中最受影响的细胞和组织中，并总结了针对钙代谢的新疗法，这些疗法可能会改善目前的治疗方案。

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引用次数: 0

Systemic lupus erythematosus and the gut microbiome: To look forward is to look within – A systematic review and narrative synthesis 系统性红斑狼疮和肠道微生物组：展望未来就是展望未来——系统回顾和叙述综合。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-26 DOI: 10.1016/j.autrev.2025.103921

Daniel Guimarães de Oliveira , Alexandra Machado , Pedro Castro Lacerda , Zoe Karakikla-Mitsakou , Carlos Vasconcelos

Background

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease shaped by complex interactions involving genetic and environmental factors. Among these, the gut microbiome is emerging as potentially modulating immune responses and influencing disease susceptibility, progression, and activity.

Objectives

To synthesize current evidence on gut microbiome changes in adult SLE patients, framed along the clinical pathway – from diagnosis to treatment – to help bridge bench and bedside for microbiome-informed SLE care and research.

Methods

A systematic search identified primary research studies examining gut microbiota in adult SLE patients. Studies were reviewed in a stepwise manner by independent investigators. Findings were synthesized narratively, emphasizing human data.

Results

SLE patients exhibit gut microbiome dysbiosis, with reduced microbial richness and altered bacterial taxa. A lower Firmicutes/Bacteroidetes ratio is frequently observed. Enrichment of specific taxa, such as Enterococcus, Lactobacillus, and Ruminococcus gnavus, is reported. Dysbiosis correlates with increased gut permeability, immune activation, and autoreactivity. Clinical associations include disease activity, flares, nephritis, and other manifestations. SLE treatments, such as hydroxychloroquine and corticosteroids, influence the microbiome. Emerging interventions such as dietary modulation and fecal microbiota transplantation show promise in early studies. However, considerable heterogeneity exists across studies in terms of patient characteristics, methodology, and taxa-level findings.

Conclusions

The gut microbiome has multifaceted associations with SLE pathogenesis, disease activity, and therapeutic response. Translation will require standardized methods, functional validation, longitudinal follow-up, and clinical integration. While uncertainties remain, the gut microbiome is increasingly relevant, and clinicians caring for patients with SLE should be aware of its emerging implications.

背景：系统性红斑狼疮（SLE）是一种异质性自身免疫性疾病，涉及遗传和环境因素的复杂相互作用。其中，肠道微生物群正在成为调节免疫反应和影响疾病易感性、进展和活动的潜在因素。目的：综合目前关于成年SLE患者肠道微生物组变化的证据，沿着临床途径（从诊断到治疗）构建框架，以帮助架起实验室和床边的桥梁，为微生物组知情的SLE护理和研究。方法：系统搜索确定了检查成年SLE患者肠道微生物群的初步研究。研究由独立调查人员逐步进行审查。研究结果综合叙述，强调人的数据。结果：SLE患者表现出肠道菌群失调，微生物丰富度降低，细菌类群改变。经常观察到较低的厚壁菌门/拟杆菌门比率。据报道，特定分类群如肠球菌、乳酸杆菌和瘤球菌的富集。生态失调与肠道通透性、免疫激活和自身反应性增加有关。临床关联包括疾病活动性、耀斑、肾炎和其他表现。SLE治疗，如羟氯喹和皮质类固醇，会影响微生物组。新兴的干预措施，如饮食调节和粪便微生物群移植在早期研究中显示出希望。然而，在患者特征、方法学和分类水平的发现方面，各研究存在相当大的异质性。结论：肠道微生物组与SLE发病机制、疾病活动性和治疗反应具有多方面的关联。翻译将需要标准化的方法、功能验证、纵向随访和临床整合。虽然不确定性仍然存在，但肠道微生物组的相关性越来越大，治疗SLE患者的临床医生应该意识到其新出现的影响。

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引用次数: 0

Updated systematic literature review and meta-analysis to inform the Italian Society of Rheumatology Recommendations on the treatment of rheumatoid arthritis-associated interstitial lung disease 更新系统文献综述和荟萃分析，以告知意大利风湿病学会关于类风湿关节炎相关间质性肺疾病治疗的建议

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-26 DOI: 10.1016/j.autrev.2025.103922

A. Fassio , M. Sebastiani , F. Pollastri , F. Cozzini , C. Crotti , N. Ughi , E. De Lorenzis , S. Mancuso , M. Radin , G. Carrara , G. Landolfi , D. Rozza , A. Manfredi

Background

rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). Despite recent guideline initiatives, no treatment recommendations specifically tailored to RA-ILD have been developed in Italy. This systematic literature review (SLR) and meta-analysis was conducted to inform the Italian Society of Rheumatology (SIR) national recommendations for the management of RA-ILD.

Methods

we conducted a systematic review and meta-analysis of studies evaluating pharmacological interventions for RA-ILD from inception up to October 2023, followed by an update up to April 2025, with a pre-defined protocol. Eligible studies included randomized controlled trials, cohort studies, and case series reporting pulmonary function outcomes, radiological progression, adverse events, and mortality. Meta-analyses were performed, and heterogeneity and publication bias were thoroughly assessed.

Results

sixty-nine studies encompassing 7879 RA-ILD patients were included. Treatments with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), rituximab (RTX), mycophenolate mofetil (MMF), abatacept (ABA), and Janus kinase inhibitors (JAKi) were associated with stabilization or improvement of forced vital capacity (FVC). Methotrexate (MTX) was associated with reduced risk of ILD progression and mortality. Antifibrotics, particularly nintedanib, demonstrated variable efficacy, while pirfenidone showed limited benefit. Safety profiles favored antifibrotics over csDMARDs/immunosuppressants regarding serious adverse events.

Conclusions

this SLR provides an updated synthesis of evidence on RA-ILD treatments, supporting the forthcoming SIR recommendations. Despite inherent limitations of observational studies and heterogeneity, the data highlight the safety of MTX and particularly support ABA, RTX, and nintedanib as promising options, while underscoring the need for further high-quality trials specifically in RA-ILD.

背景：类风湿性关节炎相关间质性肺疾病（RA- ild）是类风湿性关节炎（RA）的一种严重的关节外表现。尽管最近制定了指南，但意大利尚未制定专门针对RA-ILD的治疗建议。本系统文献综述（SLR）和荟萃分析旨在为意大利风湿病学会（SIR）提供RA-ILD管理的国家建议。方法：我们对从开始到2023年10月评估RA-ILD药物干预措施的研究进行了系统回顾和荟萃分析，随后更新到2025年4月，采用预先定义的方案。符合条件的研究包括随机对照试验、队列研究和报告肺功能结局、放射学进展、不良事件和死亡率的病例系列。进行了荟萃分析，并对异质性和发表偏倚进行了全面评估。结果纳入69项研究，共7879例RA-ILD患者。使用传统的合成疾病调节抗风湿药物（csDMARDs）、利妥昔单抗（RTX）、霉酚酸酯（MMF）、阿巴肽（ABA）和Janus激酶抑制剂（JAKi）治疗与用力肺活量（FVC）的稳定或改善相关。甲氨蝶呤（MTX）与ILD进展和死亡率降低相关。抗纤维化药物，特别是尼达尼布，表现出不同的疗效，而吡非尼酮的疗效有限。在严重不良事件方面，抗纤维化药物的安全性优于csDMARDs/免疫抑制剂。本SLR提供了关于RA-ILD治疗的最新综合证据，支持即将发布的SIR建议。尽管观察性研究存在固有的局限性和异质性，但数据强调了MTX的安全性，特别是支持ABA， RTX和nintedanib作为有希望的选择，同时强调需要进一步的高质量试验，特别是在RA-ILD中。

{"title":"Updated systematic literature review and meta-analysis to inform the Italian Society of Rheumatology Recommendations on the treatment of rheumatoid arthritis-associated interstitial lung disease","authors":"A. Fassio , M. Sebastiani , F. Pollastri , F. Cozzini , C. Crotti , N. Ughi , E. De Lorenzis , S. Mancuso , M. Radin , G. Carrara , G. Landolfi , D. Rozza , A. Manfredi","doi":"10.1016/j.autrev.2025.103922","DOIUrl":"10.1016/j.autrev.2025.103922","url":null,"abstract":"<div><h3>Background</h3><div>rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). Despite recent guideline initiatives, no treatment recommendations specifically tailored to RA-ILD have been developed in Italy. This systematic literature review (SLR) and meta-analysis was conducted to inform the Italian Society of Rheumatology (SIR) national recommendations for the management of RA-ILD.</div></div><div><h3>Methods</h3><div>we conducted a systematic review and meta-analysis of studies evaluating pharmacological interventions for RA-ILD from inception up to October 2023, followed by an update up to April 2025, with a pre-defined protocol. Eligible studies included randomized controlled trials, cohort studies, and case series reporting pulmonary function outcomes, radiological progression, adverse events, and mortality. Meta-analyses were performed, and heterogeneity and publication bias were thoroughly assessed.</div></div><div><h3>Results</h3><div>sixty-nine studies encompassing 7879 RA-ILD patients were included. Treatments with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), rituximab (RTX), mycophenolate mofetil (MMF), abatacept (ABA), and Janus kinase inhibitors (JAKi) were associated with stabilization or improvement of forced vital capacity (FVC). Methotrexate (MTX) was associated with reduced risk of ILD progression and mortality. Antifibrotics, particularly nintedanib, demonstrated variable efficacy, while pirfenidone showed limited benefit. Safety profiles favored antifibrotics over csDMARDs/immunosuppressants regarding serious adverse events.</div></div><div><h3>Conclusions</h3><div>this SLR provides an updated synthesis of evidence on RA-ILD treatments, supporting the forthcoming SIR recommendations. Despite inherent limitations of observational studies and heterogeneity, the data highlight the safety of MTX and particularly support ABA, RTX, and nintedanib as promising options, while underscoring the need for further high-quality trials specifically in RA-ILD.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103922"},"PeriodicalIF":8.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913488","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

Hedgehog signaling pathway: A research review on a new therapeutic target for rheumatoid arthritis 刺猬信号通路：类风湿关节炎治疗新靶点的研究进展

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-26 DOI: 10.1016/j.autrev.2025.103918

Yonglin Yan , Chengxia Sun , Minh Hung Hoang , Xiaojie Wang , Yongxiang Gao

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint destruction, with existing therapies limited by adverse effects and incomplete efficacy. The Hedgehog signaling pathway, abnormally activated in RA, plays a pivotal pathogenic role by promoting synovial fibroblast proliferation/invasion, amplifying inflammatory responses, inducing chondrocyte matrix degradation, and enhancing angiogenesis. This review summarizes therapeutic strategies targeting this pathway, including small-molecule inhibitors (Smo/Gli antagonists), gene therapy (CRISPR-Cas, SMO-siRNA), and emerging approaches (mesenchymal stem cells, natural products). Key findings highlight the pathway's crosstalk with JAK-STAT, IL-6 signaling, and MAPK pathways, as well as challenges such as off-target tissue toxicity, drug resistance, and unclear mechanisms underlying natural product activity. Conclusion: Targeting Hedgehog signaling holds promise for RA therapy, with future directions focusing on optimizing synovium-specific delivery, exploring combination regimens, and clarifying cell-type-specific regulatory mechanisms to accelerate clinical translation.

类风湿性关节炎（RA）是一种以进行性关节破坏为特征的慢性自身免疫性疾病，现有的治疗方法受到不良反应和疗效不完全的限制。在RA中异常激活的Hedgehog信号通路通过促进滑膜成纤维细胞增殖/侵袭、放大炎症反应、诱导软骨细胞基质降解和促进血管生成等发挥关键的致病作用。本文综述了针对该通路的治疗策略，包括小分子抑制剂（Smo/Gli拮抗剂），基因治疗（CRISPR-Cas, Smo - sirna）和新兴方法（间充质干细胞，天然产物）。主要发现强调了该通路与JAK-STAT、IL-6信号通路和MAPK通路的串扰，以及脱靶组织毒性、耐药性和天然产物活性机制不明确等挑战。结论：靶向Hedgehog信号通路有望用于RA的治疗，未来的方向将集中在优化滑膜特异性递送，探索联合方案，阐明细胞类型特异性调节机制，以加速临床转化。

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引用次数: 0

The roles of S100A8/A9 and S100A12 in autoimmune diseases: Mechanisms, biomarkers, and therapeutic potential S100A8/A9和S100A12在自身免疫性疾病中的作用：机制、生物标志物和治疗潜力

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-26 DOI: 10.1016/j.autrev.2025.103920

Xiaoqing Wang , Ying Luo , Qiang Zhou , Jie Ma

The S100 protein family, the largest group of calcium-binding proteins, functions as key molecular regulators both intracellularly and extracellularly. Among these, S100A8/A9 and S100A12 have gained particular attention for their roles in the pathogenesis of autoimmune diseases (AID). These proteins interact with pivotal receptors, including G-protein-coupled receptors (GPCRs), toll-like receptor-4 (TLR4), and receptor for advanced glycation end-products (RAGE), driving innate immune activation, amplifying inflammatory responses, and modulating immune cell function. Dysregulation of S100A8/A9 and S100A12 is closely associated with disease progression across multiple autoimmune conditions. Their elevated expression correlates with disease severity, making them valuable biomarkers for monitoring disease activity, predicting therapeutic responses, and assessing disease progression. This review provides an in-depth synthesis of current evidence on the mechanistic roles of S100A8/A9 and S100A12 in AID, emphasizing their biomarker potential and therapeutic value. We further discuss emerging therapeutic strategies that target S100 proteins, their receptors, downstream signaling pathways using small-molecule inhibitors, RNA-based approaches, and monoclonal antibodies. These insights highlight the dual promise of S100A8/A9 and S100A12 as both disease indicators and intervention points, offering novel avenues for the management of AID.

S100蛋白家族是最大的钙结合蛋白群，在细胞内和细胞外都起着关键的分子调节作用。其中，S100A8/A9和S100A12因其在自身免疫性疾病（AID）发病机制中的作用而受到特别关注。这些蛋白与关键受体相互作用，包括g蛋白偶联受体（gpcr）、toll样受体-4 （TLR4）和晚期糖基化终产物受体（RAGE），驱动先天免疫激活，放大炎症反应，调节免疫细胞功能。S100A8/A9和S100A12的失调与多种自身免疫性疾病的疾病进展密切相关。它们的升高表达与疾病严重程度相关，使其成为监测疾病活动、预测治疗反应和评估疾病进展的有价值的生物标志物。本文综述了S100A8/A9和S100A12在AID中的机制作用，强调了它们的生物标志物潜力和治疗价值。我们进一步讨论了针对S100蛋白、受体、使用小分子抑制剂、基于rna的方法和单克隆抗体的下游信号通路的新兴治疗策略。这些见解凸显了S100A8/A9和S100A12作为疾病指标和干预点的双重前景，为艾滋病的管理提供了新的途径。

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引用次数: 0

Artificial intelligence for biopsies and imaging modalities in systemic autoimmune rheumatic diseases: An instructive narrative review 人工智能在系统性自身免疫性风湿病的活检和成像模式：一个有益的叙述回顾

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-25 DOI: 10.1016/j.autrev.2025.103916

Konstantinos N. Panagiotopoulos , Nikos Tsiknakis , Dimitrios I. Zaridis , Athanasios G. Tzioufas , Dimitrios I. Fotiadis , Andreas V. Goules

Purpose

To organize the existing literature regarding applications of artificial intelligence (AI) in biopsies and imaging modalities of patients with systemic autoimmune rheumatic diseases (SARDs) and to familiarize readers with the most commonly occurring concepts.

Results

Firstly, we present a workflow that summarizes techniques implemented in AI for biopsies and imaging modalities in SARDs. Next, we describe challenges specific to image analysis for medicine. Subsequently, we describe the goals for an AI study in this field, and the prerequisites to meet them in SARDs. Finally, after reviewing the existing literature, we present the applications of AI for image analysis in each SARD. Accordingly, we analyze 1–2 studies from each SARD and mention key messages and lessons derived from them. Lastly, we create a recommendation landscape identifying unmet needs for AI applications in each SARD. The vast majority of studies employ supervised learning for image classification or segmentation, and rarely for regression. The median dataset size was 116 patients for imaging studies and 271 patients for biopsies studies, while the number of images per study varied greatly. Reporting of multiple performance metrics was frequently neglected.

Conclusions

Employing AI for SARD image analysis ultimately demands large datasets with multimodal and adequately diverse data to effectively capture the heterogeneity of SARDs. In the field of rheumatology, plagued by subjectivity and interobserver variability, issues regarding data quality, regulatory authorities and the specificity and clinical impact of questions posed will define the time needed for clinical adoption of AI-assisted medical care.

目的整理有关人工智能（AI）在系统性自身免疫性风湿性疾病（SARDs）患者活检和成像模式中的应用的现有文献，使读者熟悉最常见的概念。首先，我们提出了一个工作流，总结了在SARDs中人工智能实施的活检技术和成像模式。接下来，我们描述了医学图像分析的具体挑战。随后，我们描述了该领域人工智能研究的目标，以及在sard中满足这些目标的先决条件。最后，在回顾了现有文献后，我们介绍了人工智能在每个SARD中的图像分析应用。因此，我们分析了每个SARD的1-2项研究，并提到了从中得到的关键信息和教训。最后，我们创建了一个推荐场景，确定每个SARD中AI应用程序未满足的需求。绝大多数研究将监督学习用于图像分类或分割，很少用于回归。数据集大小中位数为影像学研究116例患者和活检研究271例患者，而每项研究的图像数量差异很大。多个性能指标的报告经常被忽略。结论采用人工智能进行SARD图像分析最终需要具有多模态和充分多样化数据的大型数据集，以有效捕获SARD的异质性。在风湿病学领域，受主观性和观察者间可变性的困扰，有关数据质量、监管当局以及所提出问题的特异性和临床影响的问题将决定临床采用人工智能辅助医疗所需的时间。

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引用次数: 0

The fragility of randomized controlled trials in large vessel vasculitis 大血管炎随机对照试验的脆弱性

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-25 DOI: 10.1016/j.autrev.2025.103917

Durga Prasanna Misra , Chetan B. Mukhtyar , Kunal Chandwar , Michael Putman , Michael Walsh

The fragility of randomized controlled trials (RCTs) of large vessel vasculitis (LVV) – defined as the minimum number of outcome events that would need to change to reverse the trial's conclusions - has not been comprehensively studied. We identified relevant RCTs with a systematic literature review till April 2025. The fragility index (FI)/ reverse fragility index (RFI) and fragility quotient (FQ, i.e., FI or RFI divided by number of trial participants) were calculated for primary or key secondary outcomes. Subgroup analyses were based on risk of bias (Cochrane Risk of Bias 2), drug (biologic or targeted synthetic agent versus other), LVV subtype, and time of publication (before/ after 2015). Eighteen RCTs (GCA, n = 14; TAK, n = 4) were analyzed. For trials with significant outcomes, FI ranged from 1 to 12 and FQ from 0.019 to 0.150; 5/9 (56 %) had FI ≤3, and 8/9 (89 %) had FQ ≤0.1. For trials with non-significant primary outcome, RFI ranged from 1 to 9 and FQ from 0.009 to 0.330; 8/12 (67 %) had RFI ≤5, 6/12 (50 %) had FQ ≤0.1, and 4/12 (33 %) had RFI less than the number lost to follow-up. The FI, RFI and FQ were similar for trials based on risk of bias, drug, LVV subtype, or time of publication. The results of most published LVV trials are fragile suggesting treatments are at risk of being misclassified as effective or ineffective. Larger trials with more robust and validated outcome measures or alternate designs should be considered in future LVV trials to improve confidence in their assessments of treatment effects.

大血管炎（LVV）的随机对照试验（rct）的脆弱性（定义为需要改变以逆转试验结论的最小结果事件数）尚未得到全面研究。我们通过系统的文献综述找到了相关的随机对照试验，直到2025年4月。计算主要或关键次要结局的脆弱性指数(FI)/反向脆弱性指数（RFI）和脆弱性商（FQ，即FI或RFI除以试验参与者数量）。亚组分析基于偏倚风险（Cochrane偏倚风险2）、药物（生物或靶向合成药物与其他药物）、LVV亚型和发表时间（2015年前后）。共分析18项rct （GCA, n = 14； TAK, n = 4）。对于具有显著结果的试验，FI范围为1至12，FQ范围为0.019至0.150；5/9 (56%) FI≤3,8/9 (89%)FQ≤0.1。对于主要结局不显著的试验，RFI范围从1到9，FQ范围从0.009到0.330；8/12（67%）患者RFI≤5,6/12（50%）患者FQ≤0.1,4/12（33%）患者RFI小于失访数。基于偏倚风险、药物、LVV亚型或发表时间的试验的FI、RFI和FQ相似。大多数已发表的LVV试验结果都是脆弱的，这表明治疗有被错误分类为有效或无效的风险。在未来的LVV试验中，应考虑采用更稳健、更有效的结果测量或替代设计的大型试验，以提高对治疗效果评估的信心。

{"title":"The fragility of randomized controlled trials in large vessel vasculitis","authors":"Durga Prasanna Misra , Chetan B. Mukhtyar , Kunal Chandwar , Michael Putman , Michael Walsh","doi":"10.1016/j.autrev.2025.103917","DOIUrl":"10.1016/j.autrev.2025.103917","url":null,"abstract":"<div><div>The fragility of randomized controlled trials (RCTs) of large vessel vasculitis (LVV) – defined as the minimum number of outcome events that would need to change to reverse the trial's conclusions - has not been comprehensively studied. We identified relevant RCTs with a systematic literature review till April 2025. The fragility index (FI)/ reverse fragility index (RFI) and fragility quotient (FQ, i.e., FI or RFI divided by number of trial participants) were calculated for primary or key secondary outcomes. Subgroup analyses were based on risk of bias (Cochrane Risk of Bias 2), drug (biologic or targeted synthetic agent versus other), LVV subtype, and time of publication (before/ after 2015). Eighteen RCTs (GCA, <em>n</em> = 14; TAK, <em>n</em> = 4) were analyzed. For trials with significant outcomes, FI ranged from 1 to 12 and FQ from 0.019 to 0.150; 5/9 (56 %) had FI ≤3, and 8/9 (89 %) had FQ ≤0.1. For trials with non-significant primary outcome, RFI ranged from 1 to 9 and FQ from 0.009 to 0.330; 8/12 (67 %) had RFI ≤5, 6/12 (50 %) had FQ ≤0.1, and 4/12 (33 %) had RFI less than the number lost to follow-up. The FI, RFI and FQ were similar for trials based on risk of bias, drug, LVV subtype, or time of publication. The results of most published LVV trials are fragile suggesting treatments are at risk of being misclassified as effective or ineffective. Larger trials with more robust and validated outcome measures or alternate designs should be considered in future LVV trials to improve confidence in their assessments of treatment effects.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103917"},"PeriodicalIF":8.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913491","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

Animal models for connective tissue disease-associated interstitial lung disease: Current status and future directions 结缔组织病相关间质性肺疾病的动物模型：现状和未来方向

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-25 DOI: 10.1016/j.autrev.2025.103919

Ziyi Tang , Hang Yang , Xiuping Liang , Jiehao Chen , Qi He , Dezhi Zhu , Yi Liu

Interstitial lung disease (ILD) significantly contributes to connective tissue disease (CTD) mortality. Although guidelines for managing CTD-associated ILD (CTD-ILD) exist, many patients respond poorly to treatment owing to two key factors: (1) incomplete understanding of subtype-specific pathogenic mechanisms, and (2) reliance on therapies adapted from systemic sclerosis or nonpulmonary rheumatic diseases, which fail to address the unique pathophysiology of distinct CTD-ILD subtypes. This hinders personalized treatment and underscores the need for robust preclinical models that accurately replicate disease-specific mechanisms. However, challenges remain: (1) the lack of models that fully capture the heterogeneity of these disorders and (2) the absence of systematic structured reviews to guide model selection, despite recent advancements in experimental methodologies. These issues often result in mismatches between research goals and model utility.

This review summarizes current CTD-ILD animal models, focusing on their construction, characteristics, and limitations, and highlighting differences between each model and the corresponding human disease. We summarize these disparities and propose emerging technologies, including CRISPR/Cas9-mediated genome editing, humanized mice, and lung organoids/lung-on-a-chip systems, that may facilitate the development of next-generation models. By integrating established and emerging strategies, we aim to provide guidance for model selection and development, promote precision modeling, accelerate targeted therapy discovery, and ultimately improve clinical outcomes. We emphasize the importance of developing subtype-specific models to avoid a “one-model-fits-all” approach.

间质性肺疾病（ILD）对结缔组织疾病（CTD）死亡率有显著影响。尽管存在治疗ctd相关ILD （CTD-ILD）的指南，但由于两个关键因素，许多患者对治疗的反应不佳：(1)对亚型特异性致病机制的理解不完整，(2)依赖于系统性硬化症或非肺类风湿性疾病的治疗，这些治疗未能解决不同CTD-ILD亚型的独特病理生理。这阻碍了个性化治疗，并强调了对准确复制疾病特异性机制的强大临床前模型的需求。然而，挑战仍然存在：(1)缺乏充分捕捉这些疾病异质性的模型；(2)尽管最近实验方法取得了进展，但缺乏系统的结构化综述来指导模型选择。这些问题往往导致研究目标与模型效用的不匹配。本文综述了目前的CTD-ILD动物模型，重点介绍了它们的构建、特点和局限性，并强调了每种模型与相应人类疾病之间的差异。我们总结了这些差异，并提出了新兴技术，包括CRISPR/ cas9介导的基因组编辑、人源化小鼠和肺类器官/肺芯片系统，这些技术可能促进下一代模型的发展。通过整合现有的和新兴的策略，我们的目标是为模型的选择和开发提供指导，促进精确建模，加速靶向治疗的发现，最终改善临床结果。我们强调开发特定亚型模型的重要性，以避免“一种模型适合所有”的方法。

{"title":"Animal models for connective tissue disease-associated interstitial lung disease: Current status and future directions","authors":"Ziyi Tang , Hang Yang , Xiuping Liang , Jiehao Chen , Qi He , Dezhi Zhu , Yi Liu","doi":"10.1016/j.autrev.2025.103919","DOIUrl":"10.1016/j.autrev.2025.103919","url":null,"abstract":"<div><div>Interstitial lung disease (ILD) significantly contributes to connective tissue disease (CTD) mortality. Although guidelines for managing CTD-associated ILD (CTD-ILD) exist, many patients respond poorly to treatment owing to two key factors: (1) incomplete understanding of subtype-specific pathogenic mechanisms, and (2) reliance on therapies adapted from systemic sclerosis or nonpulmonary rheumatic diseases, which fail to address the unique pathophysiology of distinct CTD-ILD subtypes. This hinders personalized treatment and underscores the need for robust preclinical models that accurately replicate disease-specific mechanisms. However, challenges remain: (1) the lack of models that fully capture the heterogeneity of these disorders and (2) the absence of systematic structured reviews to guide model selection, despite recent advancements in experimental methodologies. These issues often result in mismatches between research goals and model utility.</div><div>This review summarizes current CTD-ILD animal models, focusing on their construction, characteristics, and limitations, and highlighting differences between each model and the corresponding human disease. We summarize these disparities and propose emerging technologies, including CRISPR/Cas9<strong>-</strong>mediated genome editing, humanized mice, and lung organoids/lung-on-a-chip systems, that may facilitate the development of next-generation models. By integrating established and emerging strategies, we aim to provide guidance for model selection and development, promote precision modeling, accelerate targeted therapy discovery, and ultimately improve clinical outcomes. We emphasize the importance of developing subtype-specific models to avoid a “one-model-fits-all” approach.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103919"},"PeriodicalIF":8.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913490","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