Pub Date : 2026-01-05DOI: 10.1038/s41584-025-01347-1
Sruthi Vijaya Retnakumar, Jagadeesh Bayry
{"title":"Engineered sialylated IgG1 Fc as a dose-sparing alternative to IVIG","authors":"Sruthi Vijaya Retnakumar, Jagadeesh Bayry","doi":"10.1038/s41584-025-01347-1","DOIUrl":"https://doi.org/10.1038/s41584-025-01347-1","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"19 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902565","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}
Pub Date : 2025-12-19DOI: 10.1038/s41584-025-01344-4
Hance Clarke, Mary-Ann Fitzcharles
Fibromyalgia remains a challenge for researchers and clinicians. Three studies published in 2025 shed light on mechanisms and management by implicating gut microbiota in symptom perpetuation, demonstrating the potential of home-based neuromodulation, and examining the uncertain role of low-dose naltrexone.
{"title":"Progress in mechanisms and therapy for fibromyalgia","authors":"Hance Clarke, Mary-Ann Fitzcharles","doi":"10.1038/s41584-025-01344-4","DOIUrl":"10.1038/s41584-025-01344-4","url":null,"abstract":"Fibromyalgia remains a challenge for researchers and clinicians. Three studies published in 2025 shed light on mechanisms and management by implicating gut microbiota in symptom perpetuation, demonstrating the potential of home-based neuromodulation, and examining the uncertain role of low-dose naltrexone.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"84-85"},"PeriodicalIF":32.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785845","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}
Pub Date : 2025-12-19DOI: 10.1038/s41584-025-01345-3
Adam P. Croft, Annie Hackland
Advances in cellular and spatial profiling technologies have rapidly expanded the understanding of fibroblast heterogeneity within the target tissues of disease. In 2025, there has been a shift towards a consensus definition of shared cross-tissue fibroblast states and a greater understanding of their molecular drivers and disease-relevant effector functions.
{"title":"Fibroblast heterogeneity in 2025","authors":"Adam P. Croft, Annie Hackland","doi":"10.1038/s41584-025-01345-3","DOIUrl":"10.1038/s41584-025-01345-3","url":null,"abstract":"Advances in cellular and spatial profiling technologies have rapidly expanded the understanding of fibroblast heterogeneity within the target tissues of disease. In 2025, there has been a shift towards a consensus definition of shared cross-tissue fibroblast states and a greater understanding of their molecular drivers and disease-relevant effector functions.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"86-88"},"PeriodicalIF":32.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794496","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}
Pub Date : 2025-12-18DOI: 10.1038/s41584-025-01346-2
Jessica McHugh
A new study reveals that the Epstein–Barr virus can reprogramme autoreactive B cells into pathogenic antigen-presenting cells in systemic lupus erythematosus, providing a mechanistic link between infection and autoimmunity.
{"title":"Mechanistic link uncovered between EBV infection and SLE","authors":"Jessica McHugh","doi":"10.1038/s41584-025-01346-2","DOIUrl":"10.1038/s41584-025-01346-2","url":null,"abstract":"A new study reveals that the Epstein–Barr virus can reprogramme autoreactive B cells into pathogenic antigen-presenting cells in systemic lupus erythematosus, providing a mechanistic link between infection and autoimmunity.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"73-73"},"PeriodicalIF":32.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770803","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}
Pub Date : 2025-12-15DOI: 10.1038/s41584-025-01342-6
Carol A. Hitchon, Hani S. El-Gabalawy
New research published in 2025 sheds light on the pre-clinical period that precedes the onset of classifiable rheumatoid arthritis, from risk factors to immunological events and opportunities to prevent the transition to clinical disease.
{"title":"Advances in understanding preclinical rheumatoid arthritis and prospects for prevention","authors":"Carol A. Hitchon, Hani S. El-Gabalawy","doi":"10.1038/s41584-025-01342-6","DOIUrl":"10.1038/s41584-025-01342-6","url":null,"abstract":"New research published in 2025 sheds light on the pre-clinical period that precedes the onset of classifiable rheumatoid arthritis, from risk factors to immunological events and opportunities to prevent the transition to clinical disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"82-83"},"PeriodicalIF":32.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760023","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}
Pub Date : 2025-12-11DOI: 10.1038/s41584-025-01327-5
Najoua Lalaoui, Seth L. Masters
TNF is a central regulator of immune responses, inflammation and programmed cell death, and has an essential role in maintaining tissue and immune homeostasis. Abnormal TNF signalling is implicated in a broad spectrum of physiological and pathological processes, as exemplified by monogenic disorders arising from dysregulation of core components of the TNF pathway. These rare conditions encompass various autoinflammatory syndromes, immunodeficiencies, autoimmune diseases and neurodegenerative conditions, and offer unique insights into the molecular mechanisms driving pathology via TNF-mediated inflammation and cell death. Collectively, these diseases underscore the importance of tightly regulated TNF signalling for immune balance and illustrate how distinct molecular defects can produce overlapping clinical phenotypes. Variability in pathway integration and tissue-specific gene expression further shapes disease presentation, whereas disruption of post-translational modifications and cell-death regulators have emerged as central pathogenic mechanisms. Together, these insights highlight the need for precise genetic and mechanistic understanding to inform diagnosis and therapeutic strategies. Monogenic disorders involving key elements of the TNF pathway now encompass a diverse and expanding group of conditions, spanning autoinflammatory, autoimmune, immunodeficiency and neurodegenerative diseases. This Review discusses the genetic causes, clinical features and current therapeutic strategies for these disorders, emphasizing the value of accurate molecular diagnosis and targeted interventions.
{"title":"Monogenic disorders of the TNF signalling pathway","authors":"Najoua Lalaoui, Seth L. Masters","doi":"10.1038/s41584-025-01327-5","DOIUrl":"10.1038/s41584-025-01327-5","url":null,"abstract":"TNF is a central regulator of immune responses, inflammation and programmed cell death, and has an essential role in maintaining tissue and immune homeostasis. Abnormal TNF signalling is implicated in a broad spectrum of physiological and pathological processes, as exemplified by monogenic disorders arising from dysregulation of core components of the TNF pathway. These rare conditions encompass various autoinflammatory syndromes, immunodeficiencies, autoimmune diseases and neurodegenerative conditions, and offer unique insights into the molecular mechanisms driving pathology via TNF-mediated inflammation and cell death. Collectively, these diseases underscore the importance of tightly regulated TNF signalling for immune balance and illustrate how distinct molecular defects can produce overlapping clinical phenotypes. Variability in pathway integration and tissue-specific gene expression further shapes disease presentation, whereas disruption of post-translational modifications and cell-death regulators have emerged as central pathogenic mechanisms. Together, these insights highlight the need for precise genetic and mechanistic understanding to inform diagnosis and therapeutic strategies. Monogenic disorders involving key elements of the TNF pathway now encompass a diverse and expanding group of conditions, spanning autoinflammatory, autoimmune, immunodeficiency and neurodegenerative diseases. This Review discusses the genetic causes, clinical features and current therapeutic strategies for these disorders, emphasizing the value of accurate molecular diagnosis and targeted interventions.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 1","pages":"8-25"},"PeriodicalIF":32.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728613","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}
Pub Date : 2025-12-10DOI: 10.1038/s41584-025-01343-5
Huji Xu
In 2025, a new wave of ‘off-the-shelf’ B cell-depleting modalities for the treatment of autoimmune diseases emerged, encompassing allogeneic cellular therapies, in vivo chimeric antigen receptor engineering, and bispecific antibodies.
{"title":"The dawn of ‘off-the-shelf’ B cell-depleting therapies for autoimmune diseases","authors":"Huji Xu","doi":"10.1038/s41584-025-01343-5","DOIUrl":"10.1038/s41584-025-01343-5","url":null,"abstract":"In 2025, a new wave of ‘off-the-shelf’ B cell-depleting modalities for the treatment of autoimmune diseases emerged, encompassing allogeneic cellular therapies, in vivo chimeric antigen receptor engineering, and bispecific antibodies.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"78-79"},"PeriodicalIF":32.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717633","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}
Pub Date : 2025-12-08DOI: 10.1038/s41584-025-01333-7
Ivonne Melano, M. Elaine Husni, Nicolas S. Piuzzi, Suan-Sin Foo, Weiqiang Chen
Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, substantially affect quality of life, with viral infections increasingly recognized as potential but underappreciated triggers of worsening preexisting AIRD symptoms. Despite growing evidence that post-viral infections are associated with heightened autoimmune activity and disease flares, the precise mechanisms underlying the complex virus–autoimmune response remain poorly understood. As AIRD is most prevalent in women, hormonal factors might have a role in AIRD pathogenesis. Hormones can influence immune regulation, potentially affecting the risk and severity of viral-induced AIRD flares. Given the global rise of viral disease outbreaks with increasing evidence of viral persistence in AIRD pathology, this Review addresses a critical knowledge gap in understanding the immune crosstalk during viral-induced AIRD flares. We place an emphasis on emerging viruses and their potential role in AIRD flares, exploring mechanisms of immune dysregulation, chronic inflammation, molecular mimicry, viral persistence and emerging therapeutic strategies to mitigate virus-induced AIRD exacerbations. This Review is aimed at shedding light on the mechanisms by which emerging viruses promote AIRD flares, serving as a practical guide to improve clinical management and therapeutic innovations. In this Review, the authors summarize the potential role of emerging viruses in autoimmune rheumatic diseases (AIRDs). They describe the association between viruses and AIRD flare ups, the putative mechanisms linking AIRD to viral infections and hormone modulation of viral pathogenesis and autoimmune diseases.
{"title":"Emerging and underrecognized viral triggers of autoimmune inflammatory rheumatic disease flares","authors":"Ivonne Melano, M. Elaine Husni, Nicolas S. Piuzzi, Suan-Sin Foo, Weiqiang Chen","doi":"10.1038/s41584-025-01333-7","DOIUrl":"10.1038/s41584-025-01333-7","url":null,"abstract":"Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, substantially affect quality of life, with viral infections increasingly recognized as potential but underappreciated triggers of worsening preexisting AIRD symptoms. Despite growing evidence that post-viral infections are associated with heightened autoimmune activity and disease flares, the precise mechanisms underlying the complex virus–autoimmune response remain poorly understood. As AIRD is most prevalent in women, hormonal factors might have a role in AIRD pathogenesis. Hormones can influence immune regulation, potentially affecting the risk and severity of viral-induced AIRD flares. Given the global rise of viral disease outbreaks with increasing evidence of viral persistence in AIRD pathology, this Review addresses a critical knowledge gap in understanding the immune crosstalk during viral-induced AIRD flares. We place an emphasis on emerging viruses and their potential role in AIRD flares, exploring mechanisms of immune dysregulation, chronic inflammation, molecular mimicry, viral persistence and emerging therapeutic strategies to mitigate virus-induced AIRD exacerbations. This Review is aimed at shedding light on the mechanisms by which emerging viruses promote AIRD flares, serving as a practical guide to improve clinical management and therapeutic innovations. In this Review, the authors summarize the potential role of emerging viruses in autoimmune rheumatic diseases (AIRDs). They describe the association between viruses and AIRD flare ups, the putative mechanisms linking AIRD to viral infections and hormone modulation of viral pathogenesis and autoimmune diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"118-131"},"PeriodicalIF":32.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704424","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}
Pub Date : 2025-12-08DOI: 10.1038/s41584-025-01336-4
Andras Perl
Endosomal traffic governs various core processes that maintain immune homeostasis and self-tolerance, including receptor signalling, antigen processing, cytokine secretion and cellular metabolism. Traffic-regulated receptors - both intracellular and on the cell surface - modulate immune sensing of infection, nutrient availability and endogenous stress signals arising from cellular or tissue injury. In rheumatic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis, Sjögren syndrome and osteoarthritis, mounting evidence implicates disruptions in endosomal pathways as important drivers of disease onset and progression. Dysregulated endosomal trafficking contributes to type I interferon activation via signalling through Toll-like receptors, aberrant autoantigen presentation, and altered expression of metabolite transporters in immune cells and target organs. Endosome trafficking mediates autophagosome formation, the production of exosomes and the turnover of organelles, such as mitochondria that generate oxidative stress, thereby controlling chronic inflammation and connective tissue remodelling. Therefore, understanding the molecular architecture of endosomal recycling pathways and their integration with immune cell function can provide important insight into rheumatic diseases. Restoring trafficking fidelity - through modulation of RAB GTPases, endosomal Toll-like receptor signalling, metabolic reprogramming, autophagic flux and extracellular vesicle biology - represents a promising therapeutic strategy.
{"title":"Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.","authors":"Andras Perl","doi":"10.1038/s41584-025-01336-4","DOIUrl":"https://doi.org/10.1038/s41584-025-01336-4","url":null,"abstract":"Endosomal traffic governs various core processes that maintain immune homeostasis and self-tolerance, including receptor signalling, antigen processing, cytokine secretion and cellular metabolism. Traffic-regulated receptors - both intracellular and on the cell surface - modulate immune sensing of infection, nutrient availability and endogenous stress signals arising from cellular or tissue injury. In rheumatic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis, Sjögren syndrome and osteoarthritis, mounting evidence implicates disruptions in endosomal pathways as important drivers of disease onset and progression. Dysregulated endosomal trafficking contributes to type I interferon activation via signalling through Toll-like receptors, aberrant autoantigen presentation, and altered expression of metabolite transporters in immune cells and target organs. Endosome trafficking mediates autophagosome formation, the production of exosomes and the turnover of organelles, such as mitochondria that generate oxidative stress, thereby controlling chronic inflammation and connective tissue remodelling. Therefore, understanding the molecular architecture of endosomal recycling pathways and their integration with immune cell function can provide important insight into rheumatic diseases. Restoring trafficking fidelity - through modulation of RAB GTPases, endosomal Toll-like receptor signalling, metabolic reprogramming, autophagic flux and extracellular vesicle biology - represents a promising therapeutic strategy.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704701","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}
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