Nature Reviews Rheumatology最新文献_第4页

Advances in the treatment of eosinophilic granulomatosis with polyangiitis 嗜酸性肉芽肿合并多血管炎的治疗进展。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-08-04 DOI: 10.1038/s41584-026-01406-1

Adrien Cottu, Florence Roufosse, Allyson Egan, Giacomo Emmi, Matthieu Groh, Alexandra M. Nanzer, Ulrich Specks, Michael E. Wechsler, Augusto Vaglio, Benjamin Terrier

{"title":"Advances in the treatment of eosinophilic granulomatosis with polyangiitis","authors":"Adrien Cottu, Florence Roufosse, Allyson Egan, Giacomo Emmi, Matthieu Groh, Alexandra M. Nanzer, Ulrich Specks, Michael E. Wechsler, Augusto Vaglio, Benjamin Terrier","doi":"10.1038/s41584-026-01406-1","DOIUrl":"10.1038/s41584-026-01406-1","url":null,"abstract":"Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies and characterized by blood and tissue eosinophilia, severe respiratory manifestations, and multiorgan involvement. The management of newly diagnosed EGPA still relies on therapeutic strategies that were initially validated for other forms of anti-neutrophil cytoplasmic antibody-associated vasculitis, including microscopic polyangiitis and granulomatosis with polyangiitis. Whereas the long-term prognosis of microscopic polyangiitis and granulomatosis with polyangiitis depends primarily on controlling initial organ involvement and preventing relapses, EGPA is distinguished by chronic involvement of both upper and lower respiratory airways, which often necessitates prolonged glucocorticoid therapy. Data from clinical trials suggest that targeting the IL-5 pathway with mepolizumab or benralizumab can effectively control persistent respiratory symptoms and reduce the need for glucocorticoids, yet the role of these agents in the management of EGPA at the time of diagnosis and in the long term remains to be defined. Emerging retrospective data on therapies targeting other type 2 cytokines (such as IL-4, IL-13 and thymic stromal lymphopoietin) suggest potential benefits for relapsing respiratory symptoms; however, prospective evidence remains limited and safety has yet to be established. This Review discusses the role of these new targeted therapies in the management of EGPA, alongside historical treatments. The development of targeted therapeutics has transformed the management of eosinophilic granulomatosis with polyangiitis (EGPA). This Review explores the role of these new therapies, as well as that of the still-relevant historical treatments, for the induction and maintenance of remission in EGPA.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 9","pages":"541-557"},"PeriodicalIF":33.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673985","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

Navigating evidence-based recommendations for the management of systemic sclerosis 导航系统性硬化症管理的循证建议。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-08-04 DOI: 10.1038/s41584-026-01416-z

Francesco Del Galdo, Yannick Allanore, Oliver Distler, Anna Maria Hoffmann-Vold, Sindhu Johnson, Dinesh Khanna, Voon H. Ong, Elisabetta A. Renzoni, Elizabeth R. Volkmann, Christopher P. Denton

{"title":"Navigating evidence-based recommendations for the management of systemic sclerosis","authors":"Francesco Del Galdo, Yannick Allanore, Oliver Distler, Anna Maria Hoffmann-Vold, Sindhu Johnson, Dinesh Khanna, Voon H. Ong, Elisabetta A. Renzoni, Elizabeth R. Volkmann, Christopher P. Denton","doi":"10.1038/s41584-026-01416-z","DOIUrl":"10.1038/s41584-026-01416-z","url":null,"abstract":"In the past 3 years key recommendations for the management of systemic sclerosis (SSc) have been published, including updated EULAR recommendations and British Society for Rheumatology (BSR) guidelines. These recommendations are generally aligned but also reflect differences in the methodology and scope of the responsible organizations. For both EULAR and BSR, the methodology is robust and aligns with recommendations and guidelines developed for other rheumatic conditions and produced by other specialist societies. Advances in treatment and a growing evidence base for management of interstitial lung disease (ILD), a frequent complication of SSc, have informed additional relevant recommendations that include SSc-ILD. Some of these cover a broad range of ILDs that occur across systemic autoimmune rheumatic diseases, including those developed by the ACR–American College of Chest Physicians and the 2025 European Respiratory Society–EULAR clinical-practice guidelines. The American Thoracic Society has also developed recommendations for SSc-ILD. Taken together, a comparison of these published guidelines provides an overview of best practice evidence-based management that is supported by expert opinion and relevant stakeholders. By considering the overlap and similarity in recommendations and highlighting differences in approach and scope, this article helps readers to navigate an evolving treatment landscape of SSc. In this Review article, the authors compare current guidelines for systemic sclerosis, including recommendations for systemic sclerosis-associated interstitial lung disease. They emphasize the importance of alignment across guidelines to support informed clinical decision-making and patient care.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 10","pages":"605-614"},"PeriodicalIF":33.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674000","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

Metabolic exhaustion and immune ageing in rheumatoid arthritis 类风湿关节炎的代谢衰竭和免疫老化。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-08-03 DOI: 10.1038/s41584-026-01402-5

Cornelia M. Weyand, Jörg J. Goronzy

{"title":"Metabolic exhaustion and immune ageing in rheumatoid arthritis","authors":"Cornelia M. Weyand, Jörg J. Goronzy","doi":"10.1038/s41584-026-01402-5","DOIUrl":"10.1038/s41584-026-01402-5","url":null,"abstract":"Rheumatoid arthritis (RA) disproportionately affects adults over 50 years of age, highlighting how age-related immune remodelling undermines tolerance and promotes autoreactivity. In later adulthood, immune cells progressively lose metabolic resilience because of impaired nutrient sensing, reduced metabolic flexibility and disrupted anabolic–catabolic balance. In RA, these vulnerabilities are compounded by mitochondrial insufficiency across innate and adaptive immune lineages, creating a state of nutrient deprivation characterized by NAD⁺ and ATP scarcity and diversion of carbon away from oxidative phosphorylation. Mechanistic studies identify this bioenergetic fragility as a core defect that limits cellular longevity and promotes inflammatory, non-apoptotic death pathways, including pyroptosis and PANoptosis. The hypoxic, nutrient-restricted synovial environment adds pressure that exceeds the diminished metabolic adaptability of aged immune cells. In RA T cells, accelerated mitochondrial injury initiates maladaptive stress responses, disrupts mitochondria–lysosome–endoplasmic reticulum communication and induces gasdermin D-dependent pore formation and inflammatory lysis. Synovial MerTK⁺ reparative macrophages undergo a parallel metabolic crisis, whereby autocrine C1q sensing activates mitochondrial SARM1, causing NAD⁺ degradation, ATP depletion and PANoptotic cell death. Together, these findings position ageing-associated metabolic exhaustion and organelle disintegration as unifying mechanisms that convert immune cells into tissue-damaging effectors and explain the heightened susceptibility to RA in older adults. This Review examines how ageing-driven metabolic exhaustion in T cells and macrophages promotes organelle dysfunction, inflammatory cell death and chronic synovitis in rheumatoid arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 9","pages":"571-584"},"PeriodicalIF":33.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670046","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

Sex-dependent mechanisms in rheumatic diseases 风湿病的性别依赖机制。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-08-03 DOI: 10.1038/s41584-026-01405-2

Elizabeth R. Volkmann, Erica L. Herzog, Carol Feghali-Bostwick

{"title":"Sex-dependent mechanisms in rheumatic diseases","authors":"Elizabeth R. Volkmann, Erica L. Herzog, Carol Feghali-Bostwick","doi":"10.1038/s41584-026-01405-2","DOIUrl":"10.1038/s41584-026-01405-2","url":null,"abstract":"Sex differences in the prevalence, clinical phenotypes and therapeutic responses of rheumatic diseases have been recognized for decades, but the underlying mechanisms remain largely unknown. Accumulating evidence highlights the critical roles of both immune and non-immune cells in disease pathogenesis and the influence of sex hormones on cellular function. In addition, factors such as sex chromosomes, hormonal regulation, antiviral immune response, the gut microbiome and genetic and epigenetic variation probably contribute to the divergent features of rheumatic diseases between women and men. A deeper understanding of these intersecting pathways might uncover novel therapeutic targets. Thus far, treatment strategies for rheumatic diseases largely focus on immunomodulation; however, elucidating the biological basis of sex differences could enable the development of preventative therapies that target hormonal pathways and the gut microbiome, with the potential to avert both the onset and progression of these debilitating diseases to improve health for all patients. Sex-dependent mechanisms, including sex hormones, X chromosome biology, epigenetic regulation, microbiome dynamics and antiviral immunity, interact to shape immune responses and contribute to differences in susceptibility, manifestations and treatment outcomes in rheumatic diseases, highlighting opportunities for precision, sex-informed therapeutic strategies.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 9","pages":"585-595"},"PeriodicalIF":33.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670025","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

When less is more: loss of IRAK2 signalling promotes inflammation 当少即是多时：IRAK2信号的丢失会促进炎症。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-08-03 DOI: 10.1038/s41584-026-01414-1

Adriana A. de Jesus

引用次数: 0

From psoriatic plaque to synovium: decoding the skin–joint axis in psoriatic arthritis 从银屑病斑块到滑膜：解读银屑病关节炎的皮肤关节轴。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-07-31 DOI: 10.1038/s41584-026-01412-3

Maria Gabriella Raimondo, Saviana Gandolfo, Lianne S. Gensler, Ranjeny Thomas, Georg Schett, Andreas Ramming, Francesco Ciccia

{"title":"From psoriatic plaque to synovium: decoding the skin–joint axis in psoriatic arthritis","authors":"Maria Gabriella Raimondo, Saviana Gandolfo, Lianne S. Gensler, Ranjeny Thomas, Georg Schett, Andreas Ramming, Francesco Ciccia","doi":"10.1038/s41584-026-01412-3","DOIUrl":"10.1038/s41584-026-01412-3","url":null,"abstract":"Psoriatic arthritis (PsA) develops in up to 30% of individuals with psoriasis, but the mechanisms that drive progression from skin-limited disease to musculoskeletal disease remain incompletely understood. Emerging evidence supports a functional skin–joint axis in which psoriatic plaques function not only as sites of local inflammation but also as sources of immune cells capable of shaping musculoskeletal pathology. Myeloid progenitors that reside in the inflamed skin can migrate to synovial compartments; however, cell trafficking alone is insufficient to induce arthritis, as the fate of these cells is dictated by the stromal microenvironment of the musculoskeletal niche. Data from single-cell RNA sequencing, imaging mass cytometry and mitochondrial DNA lineage tracing now provide direct evidence that skin-derived myeloid precursors populate synovial tissue in people with early PsA. In parallel, T cell receptor analyses indicate that clonally related T cells are shared between psoriatic skin and inflamed joints, indicating that skin-derived T cells migrate between tissues. Together, these findings fuel a model in which PsA emerges through the convergence of high-risk skin lesions, a systemic milieu permissive to immune cell trafficking and a receptive joint stromal niche, with implications for biomarker discovery, risk stratification and disease interception. This Review synthesizes evidence for a skin–joint axis in psoriatic arthritis (PsA), highlighting key mechanisms that might drive the transition from psoriasis to PsA. The authors emphasize that further research into this axis could be important for identifying biomarkers, informing patient stratification and predicting which patients will progress to PsA.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 10","pages":"615-625"},"PeriodicalIF":33.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648869","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

Controlled release of magnesium ions shapes osteoporotic bone repair 镁离子的控制释放形成骨质疏松的骨修复。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-07-31 DOI: 10.1038/s41584-026-01418-x

Sarah Onuora

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PD-1 agonism puts the brakes on pathogenic T cell responses in RA PD-1激动作用抑制类风湿关节炎的致病性T细胞反应。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-07-30 DOI: 10.1038/s41584-026-01417-y

Holly Webster

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AI detects signs of inflammatory arthritis in hand images 人工智能可以从手部图像中检测出炎症性关节炎的迹象。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-07-28 DOI: 10.1038/s41584-026-01415-0

Cinja Nadana Koller, Thomas Hügle

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Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis 缺氧作为类风湿关节炎滑膜炎症的放大器。

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2026-07-22 DOI: 10.1038/s41584-026-01397-z

Mary Canavan, Orla Tynan, Jean Fletcher, Ursula Fearon

{"title":"Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis","authors":"Mary Canavan, Orla Tynan, Jean Fletcher, Ursula Fearon","doi":"10.1038/s41584-026-01397-z","DOIUrl":"10.1038/s41584-026-01397-z","url":null,"abstract":"Inflammatory arthritis is characterized by neovascularization, leukocyte extravasation and synovial hyperplasia, leading to joint destruction and functional disability. Although increased synovial angiogenesis is a hallmark of synovial inflammation, efficiency of the oxygen supply to the synovium is poor, leading to a hypoxic gradient that impacts differential cellular responses. This hypoxic gradient occurs as infiltrating cells and cells that reside within the joint increase their metabolic demand beyond what the highly dysregulated vasculature can supply. This hypoxic environment favours an increase in reactive oxygen species, leading to oxidative damage that further promotes inflammation. In this adverse microenvironment, synovial cells adapt to generate energy and switch their cellular metabolism from a resting regulatory state to a highly metabolically active state, enabling them to produce essential building blocks to support their proliferation. This metabolic shift results in the accumulation of metabolic intermediates that function as signalling molecules, which further dictate the inflammatory response. However, the synovium is a complex multicellular tissue, and the specific cellular reliance on oxygen and metabolites differs across the synovium. Cellular demands depend on anatomical location, cell–cell interactions and competition for nutrients. Understanding the complex interplay between hypoxia-induced signalling pathways, oxidative stress and inflammatory responses will provide a better insight into the underlying mechanisms of disease pathogenesis. In rheumatoid arthritis (RA) a hypoxic gradient develops in the synovium, which shapes inflammation and immune responses. In this Review, the authors provide insights into the role of hypoxia in the pathogenesis of RA, discuss its role in the wider integrated signalling network that drives inflammation and highlight how hypoxia can be targeted therapeutically to treat RA.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 10","pages":"626-642"},"PeriodicalIF":33.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552689","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