Autoimmunity reviews最新文献

{"title":"Autoantibody internalization in myositis skeletal muscle: Emerging evidence, mechanistic insights, and therapeutic relevance","authors":"Raphael A. Kirou ,&nbsp;Iago Pinal-Fernandez ,&nbsp;Andrew L. Mammen","doi":"10.1016/j.autrev.2025.103962","DOIUrl":"10.1016/j.autrev.2025.103962","url":null,"abstract":"<div><div>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 <em>in vivo</em> 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.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103962"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FcγRIIa in autoimmunity: Unraveling pathogenic mechanisms and therapeutic opportunities","authors":"Bo Zhu ,&nbsp;Xinhua Cao ,&nbsp;Xue Wang ,&nbsp;Luyao Yu ,&nbsp;Wenhao Zhou ,&nbsp;Lihua Zhu ,&nbsp;Qingling Yang ,&nbsp;Ke Rui","doi":"10.1016/j.autrev.2025.103974","DOIUrl":"10.1016/j.autrev.2025.103974","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 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}

{"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}

{"title":"The Trm-Treg Axis as a tissue-encoded immune checkpoint in chronic inflammation and autoimmunity","authors":"Liang Li ,&nbsp;Yumin Xia ,&nbsp;Yale Liu","doi":"10.1016/j.autrev.2025.103977","DOIUrl":"10.1016/j.autrev.2025.103977","url":null,"abstract":"<div><div>Tissue-resident memory T (Trm) cells, once heralded as gatekeepers of localized immune protection, have emerged as central players in the pathogenesis of chronic inflammation and autoimmunity at epithelial barriers. At the heart of this immunological paradox lies the dynamic interplay between Trm and regulatory T (Treg) cells—a tissue-encoded checkpoint that calibrates immune defense against the need for tolerance and repair. Disruption of this axis unleashes the latent pathogenicity of Trm cells, fueling persistent inflammation, epithelial dysfunction, and disease relapse. Here, we propose that the Trm-Treg interaction acts as a molecular rheostat that tunes immune homeostasis at barrier sites. We dissect the tissue-specific mechanisms that sustain this alliance, highlight its failure in diseases such as inflammatory bowel disease (IBD), psoriasis, and chronic obstructive pulmonary disease (COPD), and explore emerging therapeutic strategies aimed at recalibrating this immune checkpoint to restore durable epithelial tolerance.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103977"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839645","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}

{"title":"Extracellular vesicles in autoimmune diseases: Mechanistic underpinnings and precision medicine applications","authors":"Wenhui Mo ,&nbsp;Yujie Zhang ,&nbsp;Yu Zeng,&nbsp;Yanyi Zheng,&nbsp;Shenglan Zhao,&nbsp;Xiaoze Wang,&nbsp;Xiaoli Fan","doi":"10.1016/j.autrev.2025.103959","DOIUrl":"10.1016/j.autrev.2025.103959","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 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}

{"title":"Targeting age-related cell-free DNA for prevention, early diagnosis and treatment of rheumatoid arthritis","authors":"Ning Ma ,&nbsp;Yulin Xu ,&nbsp;Dingqi Zhang ,&nbsp;Huan-Tian Zhang ,&nbsp;Weidan Luo ,&nbsp;Yang Cao ,&nbsp;Vincent Kam Wai Wong","doi":"10.1016/j.autrev.2025.103961","DOIUrl":"10.1016/j.autrev.2025.103961","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 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}

{"title":"Discrepancy between international guidelines and global laboratory practices in autoantibody testing for autoimmune hepatitis","authors":"Nicola Bizzaro ,&nbsp;Dimitrios Bogdanos","doi":"10.1016/j.autrev.2025.103973","DOIUrl":"10.1016/j.autrev.2025.103973","url":null,"abstract":"","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103973"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707156","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}

{"title":"Metabolic traits of T cells and the implications in autoimmune diseases","authors":"Yi Zhou ,&nbsp;Yuqi Zhou ,&nbsp;Qing Zhu ,&nbsp;Weinan Guo ,&nbsp;Chunying Li","doi":"10.1016/j.autrev.2026.103989","DOIUrl":"10.1016/j.autrev.2026.103989","url":null,"abstract":"<div><div>The metabolic activities of T cells play a pivotal role in regulating their activation, differentiation, and effector functions. In recent years, it has emerged as a key focus of research in the maintenance of immune homeostasis and the modulation of inflammatory responses. T cells not only rely on metabolic reprogramming to meet their energy and biosynthesis demands, but also utilize intermediate metabolites to regulate epigenetic modifications and then affect gene expression and cell fate. More importantly, T cell metabolism faces adaptive pressures in tissue-specific microenvironments, which impact their effector capabilities and participate in immune tolerance maintenance. Currently, traditional immunosuppressive therapy still has limitations in the treatment of autoimmune diseases, with notable side effects. Meanwhile, targeting T cell metabolism, as an emerging strategy for intervening in autoimmune responses, has demonstrated promising potential in multiple research studies. This review provides a comprehensive overview of the metabolic characteristics of T cells at different developmental stages and functional states, explores the interactive mechanisms between metabolism and epigenetic regulation in T cells, and discusses the influence of tissue microenvironments on T cell metabolic behavior. Finally, we highlighted recent advancements in targeting T cell metabolism for treating systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. This provides new directions for developing precise clinical intervention strategies for patients with autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103989"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043549","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}

{"title":"The regulatory roles of Beta-2 glycoprotein I (β2GPI) in thrombosis and hemostasis and abnormal disease conditions developed by autoantibodies against β2GPI","authors":"Ruiying Wang ,&nbsp;Xian Wen Tan ,&nbsp;Chunyan Yu ,&nbsp;Min Li ,&nbsp;Siyu Wang ,&nbsp;Bingshu Yuan ,&nbsp;Xiaoxuan Ma ,&nbsp;Qingping Liu ,&nbsp;Eiji Matsuura ,&nbsp;Lianhua Shen","doi":"10.1016/j.autrev.2025.103984","DOIUrl":"10.1016/j.autrev.2025.103984","url":null,"abstract":"<div><div>Beta-2 glycoprotein I (β2GPI) as a core target antigen of antiphospholipid antibodies (aPLs), is a multifunctional plasma protein with phospholipid-binding properties. Under physiological conditions, β2GPI not only binds to negatively charged phospholipids via its domain V but also interacts with various molecules, such as angiostatin4.5 (AS4.5) and annexin II. These interactions play key roles in maintaining the balance between procoagulant and anticoagulant processes and in promoting angiogenesis. β2GPI binds to pathophysiological ligands, such as apoptotic cells, oxidized low-density lipoprotein (oxLDL) and neutrophil extracellular traps (NETs). These complexes can trigger the production of anti-β2GPI autoantibodies in autoimmune patients, leading to antiphospholipid syndrome (APS). The resulting IgG immune complexes activate and impair endothelial cells, resulting in aberrant activation of the coagulation cascade, disruption of lipid metabolic homeostasis, and breakdown of immune tolerance. Together, these processes promote thrombotic events in APS and accelerate the progression of atherosclerotic plaques. This review paper summaries the dynamic conformational transitions of β2GPI's functional domains that elucidates the dual regulatory role of β2GPI-mediated molecular interactions in thrombosis and atherosclerosis (AS) and reveals the mechanism by which anti-β2GPI autoantibodies mediate endothelial injury, thrombosis, and inflammatory amplification. These findings may provide a theoretical molecular basis for the development of novel diagnostic and therapeutic strategies targeting β2GPI.</div></div><div><h3>Take home message</h3><div><ul><li><span>•</span><span><div>β2GPI maintains the balance between procoagulant and anticoagulant processes and regulates angiogenesis.</div></span></li><li><span>•</span><span><div>Under pathological conditions, immune complexes of β2GPI with multiple molecules such as PS, oxLDL and PF4 drive the pathological cascade of endothelial damage-thrombosis-inflammatory amplification.</div></span></li><li><span>•</span><span><div>Dual-domain targeting (e.g., for stabilizing of DI-DV interaction) to mask antigenicity of β2GPI is potentially useful for inhibiting pathogenic antibody production.</div></span></li></ul></div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103984"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896192","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}

{"title":"The metabolic landscape of connective tissue diseases: Applications and discoveries in metabolomics research","authors":"Yinlan Wu ,&nbsp;Daihua Deng ,&nbsp;Yanhong Li ,&nbsp;Sijun Zhang ,&nbsp;Tong Wu ,&nbsp;Deying Huang ,&nbsp;Lu Cheng ,&nbsp;Yi Liu ,&nbsp;Chunyu Tan ,&nbsp;Yubin Luo","doi":"10.1016/j.autrev.2025.103975","DOIUrl":"10.1016/j.autrev.2025.103975","url":null,"abstract":"<div><div>Metabolomics has significantly advanced our understanding of connective tissue diseases (CTDs) in recent years by revealing the complex metabolic alterations that underlie these autoimmune disorders. This comprehensive review synthesizes current knowledge on how metabolomics elucidates CTDs pathogenesis, enhances diagnostic precision, and guides therapeutic interventions. Central to this discussion are pivotal metabolic pathways—including those of amino acids, lipids, and carbohydrates—which exhibit distinct dysregulation patterns across different CTDs. These metabolic shifts not only reflect disease activity and severity but also offer potential biomarkers for early detection and monitoring. Advanced metabolomic technologies have facilitated the identification of novel therapeutic targets by uncovering the metabolic networks that govern immune responses and inflammation. Furthermore, metabolomics bridges the gap between host metabolism and gut microbiota, shedding light on how microbial metabolites influence immune homeostasis and disease progression. The integration of metabolomics with other omics disciplines promises a more holistic understanding of CTDs, paving the way for personalized medicine. This review highlights the transformative potential of metabolomics in CTDs research, underscoring its role in uncovering the molecular mechanisms driving these diseases and inspiring innovative management and treatment strategies.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103975"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720840","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}