Autoimmunity reviews最新文献

{"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}

{"title":"Therapeutic approaches in adults with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A review of current evidence","authors":"Jakob Stögbauer ,&nbsp;Victoria Schegerer ,&nbsp;Clemens Klein ,&nbsp;Marc Pawlitzki ,&nbsp;Sven G. Meuth ,&nbsp;Orhan Aktas ,&nbsp;Sergiu Groppa ,&nbsp;Mathias Fousse","doi":"10.1016/j.autrev.2025.103970","DOIUrl":"10.1016/j.autrev.2025.103970","url":null,"abstract":"<div><div>Recent years have seen a considerable increase in knowledge pertaining to Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD). Nevertheless, a noteworthy degree of uncertainty remains within the neurological community, primarily due to the often highly heterogeneous nature of the disease and the absence of approved long-term treatment options. In this article, we undertake a comprehensive review of the various treatment strategies and drug options available for the pharmacological treatment of acute attacks and relapses in MOGAD.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103970"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676187","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":"LAG-3 in (auto)immunity and cancer - Emphasising its role in antigen presenting cells","authors":"Aleksandra Wiśniewska ,&nbsp;Elżbieta Sarnowska ,&nbsp;Katarzyna Kozak ,&nbsp;Piotr Rutkowski ,&nbsp;Paweł Sobczuk","doi":"10.1016/j.autrev.2026.103992","DOIUrl":"10.1016/j.autrev.2026.103992","url":null,"abstract":"<div><div>The growing popularity of immunotherapy shows a promising future for cancer treatment. However, a significant need to develop new therapeutics that could be successfully used in therapy still remains, especially in “immune-cold” tumors that are not responsive to classic anti-PD-1 treatment. Therefore, the discovery of lymphocyte activation gene-3 (LAG-3) as a new immune checkpoint (IC) molecule that physiologically participates in auto-tolerance mechanisms preventing auto-aggression was a significant milestone in immuno-oncology. Two main approaches aim to introduce LAG-3-directed therapies into clinical practice: anti-LAG-3 antibodies that are meant to inhibit LAG-3 function and recombinant soluble LAG-3 form that aim to activate immune response, especially by interacting with the antigen-presenting cells (APCs). So far, studies show that both approaches may be safe and effective anti-cancer treatment options. This review summarises the role of LAG-3 in immune response and emphasises the role of this IC molecule and its soluble form on APCs function, while also noting the primary physiological function of LAG-3 in autoimmunity and providing a dual perspective of the pros and cons of this novel anti-cancer therapy.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103992"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050122","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":"Gastrointestinal histology of systemic sclerosis: A systematic review","authors":"Aidan K. Strother ,&nbsp;Robert M. Anderton ,&nbsp;Naveen Kalavar ,&nbsp;Ali Y. Ayla ,&nbsp;Tracy Ashby ,&nbsp;Amanda Mayer ,&nbsp;Roshan Dongre ,&nbsp;Francesco Bonomi ,&nbsp;Silvia Bellando Randone ,&nbsp;Michael Hughes ,&nbsp;Zsuzsanna H. McMahan","doi":"10.1016/j.autrev.2026.103988","DOIUrl":"10.1016/j.autrev.2026.103988","url":null,"abstract":"<div><h3>Objective</h3><div>To systematically review and synthesize the histological findings of gastrointestinal (GI) tissue in patients with systemic sclerosis (SSc), aiming to clarify the role of fibrosis and other pathological processes in SSc-related GI disease.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across MEDLINE (OVID), Web of Science, and Cochrane Library databases for studies published in English from 1960 to 2025. Inclusion criteria required studies to report qualitative histological findings from GI tissue (esophagus to anorectum) in adult SSc patients, excluding those with overlapping autoimmune diseases or malignancy. Data extraction and appraisal were performed independently by multiple reviewers.</div></div><div><h3>Results</h3><div>Of 1697 screened articles, 36 met inclusion criteria. Histological analysis revealed that fibrosis, while common, was not universal nor evenly distributed across GI layers. The mucosa predominantly exhibited inflammatory infiltrates (mast cells, macrophages, lymphocytes), villous atrophy, and less frequent fibrosis. Submucosal findings were inconsistent, with variable reports of vascular changes and nerve plexus degeneration. The muscularis layer showed near-universal smooth muscle atrophy and variable fibrosis, with decreased density of interstitial cells of Cajal (ICC) in some studies. Neuronal and mitochondrial pathology were underreported.</div></div><div><h3>Conclusion</h3><div>GI pathology in SSc is multifaceted, involving inflammation, cellular degeneration, neuronal dysfunction, and smooth muscle atrophy, with fibrosis as a variable feature. Standardization of histological reporting and further ultrastructural studies are needed to elucidate mechanisms and guide future research and therapeutic strategies.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 2","pages":"Article 103988"},"PeriodicalIF":8.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043592","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":"Ferritinophagy in inflammatory and autoimmune diseases: Mechanistic insights and therapeutic potentials","authors":"Yi Wang ,&nbsp;Yang Li ,&nbsp;Jiani Jiang ,&nbsp;Yanggang Hong ,&nbsp;Sheng Gao ,&nbsp;Chunyan Hua","doi":"10.1016/j.autrev.2025.103954","DOIUrl":"10.1016/j.autrev.2025.103954","url":null,"abstract":"<div><div>Ferritinophagy, a selective form of autophagy mediated by nuclear receptor coactivator 4 (NCOA4), degrades ferritin to regulate intracellular iron homeostasis and has emerged as an important process in inflammatory and autoimmune diseases. By controlling ferritin turnover, ferritinophagy affects labile iron levels and ferroptosis, an iron-dependent cell death driven by lipid peroxidation, and interacts with multiple immune regulatory pathways. This process is modulated by signaling networks such as MAPK, cGAS-STING, NF-κB, AMPK/mTOR, and NRF2, which link iron metabolism to inflammatory responses. Aberrant ferritinophagy has been implicated in conditions including sepsis, osteoarthritis, asthma, rheumatoid arthritis, and systemic lupus erythematosus. Preclinical studies demonstrate that strategies such as inhibiting the JNK-JUN or cGAS-STING pathways, or applying iron chelators like deferoxamine, can reduce iron overload, limit ferroptosis, and attenuate inflammation. Despite these advances, further work is needed to delineate disease-specific regulatory mechanisms and to translate ferritinophagy modulation into safe and effective therapies. This review summarizes current mechanistic insights and therapeutic prospects, highlighting ferritinophagy as a promising target for managing inflammatory and autoimmune disorders.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103954"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426344","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":"Regulated cell death in systemic lupus erythematosus: Key pathways and targeted therapies","authors":"Siying Deng,&nbsp;Ziwei Hu,&nbsp;Shaozhe Cai,&nbsp;Lingli Dong","doi":"10.1016/j.autrev.2025.103958","DOIUrl":"10.1016/j.autrev.2025.103958","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by pathological auto-antibody production and severe immune dysregulation. Dysfunction in regulated cell death (RCD) pathways is crucial in SLE development. Abnormal cell death and cell debris clearance disorder within tissues promote the exposure and accumulation of auto-antigens, activate self-reaction B cells, and amplify interferon type I (IFN-I) reaction. Meanwhile, immune microenvironment disorder caused by abnormal RCD of immune cells exacerbate this response. The review systematically expounds the pathogenic mechanisms of both classical and novel RCD pathways in SLE. By comparing shared and disease-specific RCD dysregulation between SLE and other autoimmune diseases, we evaluate innovative RCD-targeted therapies, offering new insights on SLE pathogenesis and precision treatment.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103958"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562454","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}