Autoimmunity reviews最新文献_第4页

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。

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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。

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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。

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引用次数: 0

Systemic sclerosis and AHR: Shedding light on a hidden connections 系统性硬化和AHR：揭示隐藏的联系

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-20 DOI: 10.1016/j.autrev.2025.103915

Anna Wajda , Agnieszka Paradowska-Gorycka , Charlotte Esser

Systemic sclerosis (SSc) is a complex and debilitating autoimmune disease marked by fibrosis of the skin and inner organs, alongside chronic inflammation, and vascular abnormalities. SSc pathogenesis involves both genetic and environmental factors, such as silica dust or benzene exposure but the underlying molecular mechanisms regulating fibrogenesis and organ involvement are not fully understood. In part due to this knowledge gap, treatment options are limited. In this review we look at the possible role of the aryl hydrocarbon receptor (AHR), a transcription factor involved in immunomodulation, fibrosis and drug metabolism and inflammatory responses, especially in barrier organs. AHR activation by binding to one of its many small molecular weight ligands can result in gene-expression changes in the nucleus (its role as a transcription factor) but also lead to knock-on effects on other signaling pathways via direct binding (e.g., to NFkB) or via AHR's protein degradation capacity (E3 ligase). In some cell types transcription target genes include the fibrogenic cytokine TGF-β or metalloproteinases responsible for extracellular matrix remodeling. AHR has been shown to be highly expressed in all cutaneous cell populations, and to be critical for skin homeostasis. Given its context-dependent effects, AHR may act as both a pro- and anti-fibrotic regulator in SSc, depending on ligand availability and cellular environment. This dual role highlights AHR as a potential therapeutic target, where selective agonists or antagonists could help restore immune and fibrotic homeostasis. Here, we explore these mechanisms and discuss the potential of AHR as a therapeutic target for modulating disease progression and improving patient outcomes.

系统性硬化症（SSc）是一种复杂的、使人衰弱的自身免疫性疾病，其特征是皮肤和内脏纤维化，同时伴有慢性炎症和血管异常。SSc的发病机制涉及遗传和环境因素，如二氧化硅粉尘或苯暴露，但调节纤维发生和器官受损伤的潜在分子机制尚不完全清楚。部分由于这种知识差距，治疗选择是有限的。在这篇综述中，我们着眼于芳烃受体（AHR）的可能作用，芳烃受体是一种转录因子，参与免疫调节、纤维化、药物代谢和炎症反应，特别是在屏障器官中。AHR通过与其众多小分子量配体中的一种结合而激活，可导致细胞核中基因表达的变化（其作为转录因子的作用），但也会通过直接结合（例如，与NFkB）或通过AHR的蛋白质降解能力（E3连接酶）对其他信号通路产生连锁反应。在某些细胞类型中，转录靶基因包括纤维化细胞因子TGF-β或负责细胞外基质重塑的金属蛋白酶。AHR已被证明在所有皮肤细胞群中高度表达，并且对皮肤稳态至关重要。鉴于其上下文依赖效应，AHR可能在SSc中作为促纤维化和抗纤维化调节剂，这取决于配体的可用性和细胞环境。这种双重作用突出了AHR作为潜在的治疗靶点，选择性激动剂或拮抗剂可以帮助恢复免疫和纤维化的稳态。在这里，我们探讨了这些机制，并讨论了AHR作为调节疾病进展和改善患者预后的治疗靶点的潜力。

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引用次数: 0

In search of biomarkers for prediction of drug treatment responses in rheumatoid arthritis: Lessons learned and future perspectives 寻找类风湿性关节炎药物治疗反应预测的生物标志物：经验教训和未来展望

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-20 DOI: 10.1016/j.autrev.2025.103914

Athanasia Dara, Nikolaos I. Vlachogiannis, George E. Fragoulis, Maria G. Tektonidou, Petros P. Sfikakis

Prompt initiation of effective drug treatment is crucial for controlling inflammation and preventing disease progression in rheumatoid arthritis, the most prevalent systemic rheumatic disease. The growing range of drug therapies over the past three decades and the fact that only a minority of patients achieve sustained long-term remission with any given therapy, make imperative the need for biomarkers predicting responses to specific drugs. Moreover, promising therapeutic approaches under development, namely cellular therapies, could be promptly applicable at earlier disease stages in about 10-15 % of RA patients who will be refractory to all approved drugs. In this scoping review of original articles published until 25th of July 2025, we present a critical overview of the literature pertaining to the prognostic value of blood immunophenotyping, circulating proteins and blood proteomics, transcriptomics, metabolomics and lipidomics, as well as of endogenous cortisol production and synovial histopathology. We also discuss the emerging use of artificial intelligence-based approaches for developing response prediction models that integrate clinical features with molecular profiling. We conclude that current knowledge does not allow to discern future responders to methotrexate and/or to different biologic agents from non-responders because established biomarkers to identify those patients who will benefit the most from each therapeutic option are lacking. We also emphasize the lack of standardized research approaches to discover biomarkers predicting drug treatment responses and try to identify the relevant pitfalls and describe the lessons learned over the years. Finally, we propose a roadmap and the application of advanced analytical and machine learning techniques for future research in this area.

类风湿性关节炎是最普遍的系统性风湿性疾病，及时开始有效的药物治疗对于控制炎症和预防疾病进展至关重要。在过去的三十年中，药物治疗的范围不断扩大，而且只有少数患者通过任何给定的治疗获得持续的长期缓解，这使得对生物标志物预测特定药物反应的需求势在必行。此外，正在开发的有希望的治疗方法，即细胞疗法，可以迅速应用于大约10- 15%的RA患者的早期疾病阶段，这些患者对所有批准的药物都是难治性的。在这篇截至2025年7月25日发表的原创文章的范围综述中，我们提出了关于血液免疫表型、循环蛋白和血液蛋白质组学、转录组学、代谢组学和脂质组学以及内源性皮质醇产生和滑膜组织病理学的预后价值的文献综述。我们还讨论了基于人工智能的方法的新兴应用，用于开发将临床特征与分子谱相结合的反应预测模型。我们得出的结论是，目前的知识无法区分未来对甲氨蝶呤和/或不同生物制剂的反应者和无反应者，因为缺乏确定将从每种治疗方案中获益最多的患者的既定生物标志物。我们还强调缺乏标准化的研究方法来发现预测药物治疗反应的生物标志物，并试图确定相关的陷阱，并描述多年来吸取的教训。最后，我们为该领域的未来研究提出了路线图和先进的分析和机器学习技术的应用。

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引用次数: 0

Rapid radiographic progression in rheumatoid arthritis: Definition, prediction and treatment 类风湿关节炎的快速影像学进展：定义、预测和治疗。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-18 DOI: 10.1016/j.autrev.2025.103913

Bo Lv , Fanshu Li , Fanlei Hu , Liling Xu

Rapid radiographic progression (RRP) in rheumatoid arthritis (RA) is strongly correlated with unfavorable long-term prognostic outcomes. Early identification of RRP is paramount, as prompt intervention and the implementation of intensified therapeutic regimens have the potential to substantially improve clinical outcomes. This review summarized the different definitions and current key predictors of RRP, such as genetic predispositions, body mass index and so on. Furthermore, the existing matrix-based predictive models for RRP were compared. In addition, the potential treatment options for patients with RRP were also outlined. The objective of this review is to improve the early detection of RRP, thereby facilitating timely intervention and the adoption of personalized treatment paradigms that optimize patient prognosis.

类风湿关节炎（RA）的放射学快速进展（RRP）与不良的长期预后密切相关。早期识别RRP是至关重要的，因为及时干预和强化治疗方案的实施有可能大大改善临床结果。本文综述了RRP的不同定义和目前的主要预测因素，如遗传易感性、体重指数等。并对现有的基于矩阵的RRP预测模型进行了比较。此外，还概述了RRP患者的潜在治疗方案。本综述的目的是提高RRP的早期发现，从而促进及时干预和采用个性化治疗模式，优化患者预后。

引用次数: 0