{"title":"Insights into Lyme arthritis","authors":"Holly Webster","doi":"10.1038/s41584-025-01269-y","DOIUrl":"https://doi.org/10.1038/s41584-025-01269-y","url":null,"abstract":"Two complimentary studies provide a deeper understanding of Lyme disease and the associated chronic complications, such as Lyme arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"4 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153589","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":"How JAK inhibitors tip the prothrombotic balance in rheumatoid arthritis","authors":"Vibeke Strand","doi":"10.1038/s41584-025-01263-4","DOIUrl":"https://doi.org/10.1038/s41584-025-01263-4","url":null,"abstract":"The increased incidence of deep vein thromboses and pulmonary emboli has long been noted in rheumatoid arthritis and has been ascribed to the effects of chronic inflammation and disease activity, as well as to specific biologic DMARDs and JAK inhibitors. Reporting in ACR Open Rheumatology, Zavoriti and Miossec provide data that might explain the prothrombotic effects of the JAK inhibitor tofacitinib.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"5 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066214","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}
Angela E. Zou, Suppawat Kongthong, Alisa A. Mueller, Michael B. Brenner
{"title":"Fibroblasts in immune responses, inflammatory diseases and therapeutic implications","authors":"Angela E. Zou, Suppawat Kongthong, Alisa A. Mueller, Michael B. Brenner","doi":"10.1038/s41584-025-01259-0","DOIUrl":"https://doi.org/10.1038/s41584-025-01259-0","url":null,"abstract":"<p>Once regarded as passive bystander cells of the tissue stroma, fibroblasts have emerged as active orchestrators of tissue homeostasis and disease. From regulating immunity and controlling tissue remodelling to governing cell growth and differentiation, fibroblasts assume myriad roles in guiding normal tissue development, maintenance and repair. By comparison, in chronic inflammatory diseases such as rheumatoid arthritis, fibroblasts recruit and sustain inflammatory leukocytes, become dominant producers of pro-inflammatory factors and catalyse tissue destruction. In other disease contexts, fibroblasts promote fibrosis and impair host control of cancer. Single-cell studies have uncovered striking transcriptional and functional heterogeneity exhibited by fibroblasts in both normal tissues and diseased tissues. In particular, advances in the understanding of fibroblast pathology in rheumatoid arthritis have shed light on pathogenic fibroblast states in other chronic diseases. The differentiation and activation of these fibroblast states is driven by diverse physical and chemical cues within the tissue microenvironment and by cell-intrinsic signalling and epigenetic mechanisms. These insights into fibroblast behaviour and regulation have illuminated therapeutic opportunities for the targeted deletion or modulation of pathogenic fibroblasts across many diseases.</p>","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"122 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979459","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}
Ahmet Gül, Ivona Aksentijevich, Paul Brogan, Marco Gattorno, Peter C. Grayson, Seza Ozen
{"title":"The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis","authors":"Ahmet Gül, Ivona Aksentijevich, Paul Brogan, Marco Gattorno, Peter C. Grayson, Seza Ozen","doi":"10.1038/s41584-025-01250-9","DOIUrl":"https://doi.org/10.1038/s41584-025-01250-9","url":null,"abstract":"<p>Many monogenic autoinflammatory diseases, including DADA2 (deficiency of adenosine deaminase 2), HA20 (haploinsufficiency of A20), SAVI (STING-associated vasculopathy with onset in infancy), COPA syndrome, LAVLI (LYN kinase-associated vasculopathy and liver fibrosis) and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, present predominantly with vasculitis and constitute a substantial subgroup of vasculitic conditions associated with a ‘probable aetiology’. The spectrum of monogenic vasculitis encompasses all sizes and types of blood vessel, ranging from large vessels to medium-size and small vessels, and from the arterial side to the venous side of the vasculature. Monogenic vasculitis typically starts early in life during infancy or childhood; VEXAS syndrome, which presents in late adulthood, is an exception. The activation of myeloid cells via inflammasome and nuclear factor-κB pathways, type I interferon-enhanced autoimmune mechanisms and/or dysregulated adaptive immune responses have an important role in the development of immune-mediated endothelial dysfunction and vascular damage. Genetic testing is essential for the diagnosis of underlying monogenic autoinflammatory diseases; however, the penetrance of genetic variants can vary. Increased awareness and recognition of distinctive clinical findings could facilitate earlier diagnosis and allow for more-targeted treatments.</p>","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"3 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945762","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":"Region-specific, data-driven guidelines are needed for rheumatic diseases in LMICs","authors":"Amita Aggarwal","doi":"10.1038/s41584-025-01265-2","DOIUrl":"https://doi.org/10.1038/s41584-025-01265-2","url":null,"abstract":"Separate guidelines are needed for the management and diagnosis of rheumatic diseases in low- and middle-income countries, especially with the advent of expensive biological therapies and monitoring techniques. The lack of robust data on the efficacy of low-cost drugs and biosimilars in these countries limits the development of data-driven guidelines.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"44 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933545","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":"Understanding rheumatic disease through continuous cell state analysis","authors":"Lysette Marshall, Soumya Raychaudhuri, Sebastien Viatte","doi":"10.1038/s41584-025-01253-6","DOIUrl":"https://doi.org/10.1038/s41584-025-01253-6","url":null,"abstract":"<p>Autoimmune rheumatic diseases are a heterogeneous group of conditions, including rheumatoid arthritis (RA) and systemic lupus erythematosus. With the increasing availability of large single-cell datasets, novel disease-associated cell types continue to be identified and characterized at multiple omics layers, for example, ‘T peripheral helper’ (T<sub>PH</sub>) (CXCR5<sup>−</sup> PD-1<sup>hi</sup>) cells in RA and systemic lupus erythematosus and MerTK<sup>+</sup> myeloid cells in RA. Despite efforts to define disease-relevant cell atlases, the very definition of a ‘cell type’ or ‘lineage’ has proven controversial as higher resolution assays emerge. This Review explores the cell types and states involved in disease pathogenesis, with a focus on the shifting perspectives on immune and stromal cell taxonomy. These understandings of cell identity are closely related to the computational methods adopted for analysis, with implications for the interpretation of single-cell data. Understanding the underlying cellular architecture of disease is also crucial for therapeutic research as ambiguity hinders translation to the clinical setting. We discuss the implications of different frameworks for cell identity for disease treatment and the discovery of predictive biomarkers for stratified medicine — an unmet clinical need for autoimmune rheumatic diseases.</p>","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"12 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920033","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 anti-PAD4 autoantibodies in RA","authors":"Holly Webster","doi":"10.1038/s41584-025-01264-3","DOIUrl":"https://doi.org/10.1038/s41584-025-01264-3","url":null,"abstract":"Findings implicate anti-PAD4 antibodies in the pathogenesis of rheumatoid arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"53 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909896","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":"Arterial and venous thrombosis in systemic and monogenic vasculitis.","authors":"Federica Bello,Filippo Fagni,Giacomo Bagni,Catherine L Hill,Aladdin J Mohammad,Sergey Moiseev,Iacopo Olivotto,Emire Seyahi,Giacomo Emmi","doi":"10.1038/s41584-025-01252-7","DOIUrl":"https://doi.org/10.1038/s41584-025-01252-7","url":null,"abstract":"Systemic vasculitis, common forms of which include anti-neutrophil cytoplasmic antibody-associated small-vessel vasculitis, large-vessel vasculitis and Behçet syndrome, are frequently complicated by arterial or venous thrombotic events (AVTEs). Newly identified entities such as DADA2 (deficiency of adenosine deaminase 2) and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, which are driven by genetic mutations, also exhibit vasculitic features and are associated with a high risk of AVTEs. AVTEs in systemic vasculitis, including monogenic forms of vasculitis, are due to the complex interaction of inflammation and coagulation. New insights into the pathogenetic mechanisms implicate endothelial dysfunction, immune complex deposition and the interplay of pro-inflammatory cytokines with prothrombotic factors, which collectively promote thrombus formation. AVTEs impose a substantial disease burden, complicate diagnosis and negatively affect prognosis by increasing the risk of morbidity and mortality. Early diagnosis and treatment are crucial to prevent lasting damage. Management strategies should target both thrombosis and underlying inflammation. Antithrombotic therapies, including low-dose aspirin, or oral anticoagulants should be used on the basis of individual thrombotic risk assessment. Immunosuppressive therapy is the cornerstone of treatment for arterial and venous thrombosis, particularly in Behçet syndrome, in which vascular inflammation has a crucial role in thrombotic complications.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"56 3 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915091","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":"Risks and benefits of immunosuppressant withdrawal in systemic lupus erythematosus","authors":"Catriona A. Wagner, Judith A. James","doi":"10.1038/s41584-025-01262-5","DOIUrl":"https://doi.org/10.1038/s41584-025-01262-5","url":null,"abstract":"Withdrawing immunosuppressive treatment in systemic lupus erythematosus offers reduced toxicity and improved quality of life for patients in remission but carries a risk of disease reactivation. Emerging studies emphasize the importance of identifying patients who can safely discontinue therapy using clinical criteria and molecular profiling to guide personalized strategies.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901314","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":"Glycosylation switch in synovial fibroblasts promotes ECM degradation","authors":"Holly Webster","doi":"10.1038/s41584-025-01258-1","DOIUrl":"https://doi.org/10.1038/s41584-025-01258-1","url":null,"abstract":"Activation of N-acetylgalactosaminyltransferases in synovial fibroblasts promotes the degradation of the extracellular matrix in arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862087","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}