Pub Date : 2025-06-16DOI: 10.1038/s41584-025-01267-0
Eduardo Patiño-Martinez, Mariana J. Kaplan
Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by chronic inflammation, tissue damage, accelerated cardiovascular disease and the synthesis of autoantibodies that target nucleic acids and nuclear protein complexes. Emerging evidence underscores the key role of immune metabolic dysregulation in SLE, revealing how metabolic reprogramming during immune cell activation influences disease development and progression. Alterations in key metabolic pathways such as glycolysis and oxidative phosphorylation profoundly affect the activation, differentiation and function of B and T cells, monocytes, neutrophils and other immune cells, driving inflammation and tissue injury. This Review synthesizes current findings on immune cell metabolism in animal models of lupus and in patients with SLE, highlighting the interplay of metabolic disturbances, mitochondrial dysfunction and disease pathogenesis. Furthermore, it explores the potential of targeting metabolic pathways as therapeutic strategies to mitigate organ damage and improve outcomes in SLE. Systemic lupus erythematosus is characterized by altered metabolic profiles and changes in immune cell metabolism. The authors review these changes and discuss how interventions that target metabolic processes might provide treatment options in systemic lupus erythematosus.
{"title":"Immunometabolism in systemic lupus erythematosus","authors":"Eduardo Patiño-Martinez, Mariana J. Kaplan","doi":"10.1038/s41584-025-01267-0","DOIUrl":"10.1038/s41584-025-01267-0","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by chronic inflammation, tissue damage, accelerated cardiovascular disease and the synthesis of autoantibodies that target nucleic acids and nuclear protein complexes. Emerging evidence underscores the key role of immune metabolic dysregulation in SLE, revealing how metabolic reprogramming during immune cell activation influences disease development and progression. Alterations in key metabolic pathways such as glycolysis and oxidative phosphorylation profoundly affect the activation, differentiation and function of B and T cells, monocytes, neutrophils and other immune cells, driving inflammation and tissue injury. This Review synthesizes current findings on immune cell metabolism in animal models of lupus and in patients with SLE, highlighting the interplay of metabolic disturbances, mitochondrial dysfunction and disease pathogenesis. Furthermore, it explores the potential of targeting metabolic pathways as therapeutic strategies to mitigate organ damage and improve outcomes in SLE. Systemic lupus erythematosus is characterized by altered metabolic profiles and changes in immune cell metabolism. The authors review these changes and discuss how interventions that target metabolic processes might provide treatment options in systemic lupus erythematosus.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"377-395"},"PeriodicalIF":32.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296012","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 : 2025-06-10DOI: 10.1038/s41584-025-01268-z
Manuel Ramos-Casals, Alan N. Baer, María del Pilar Brito-Zerón, Katherine M. Hammitt, Coralie Bouillot, Soledad Retamozo, Alison Mackey, David Yarowsky, Breck Turner, Jaime Blanck, Benjamin A. Fisher, Esen K. Akpek, Chiara Baldini, Hendrika Bootsma, Simon J. Bowman, Thomas Dörner, Leslie Laing, Scott M. Lieberman, Xavier Mariette, Stephen C. Pflugfelder, Vidya Sankar, Antoni Sisó-Almirall, Athanasios G. Tzioufas, Juan-Manuel Anaya, Berkan Armağan, Michele Bombardieri, Steven Carsons, Salvatore de Vita, Robert I. Fox, Roberto Gerli, Roberto Giacomelli, Jacques Eric Gottenberg, Gabriela Hernández-Molina, Roland Jonsson, Aike Kruize, Seung-Ki Kwok, Xiaomei Li, Sara S. McCoy, Wan-Fai Ng, Peter Olsson, Maureen Rischmueller, Alain Saraux, R. Hal Scofield, Valéria Valim, Claudio Vitali, Frederick Vivino, Marie Wahren-Herlenius, Haralampos M. Moutsopoulos, on behalf of the International Task Force on Nomenclature of Sjögren Disease
Nomenclature for the disease widely known as Sjögren syndrome has proven unsatisfactory. Patients have perceived ‘syndrome’ as indicative of a vague collection of symptoms, prompting the Sjögren’s Foundation to abandon the term. Furthermore, the traditional distinction between ‘primary’ and ‘secondary’ forms fails to account for the complex interplay between overlapping autoimmune diseases. Following a bibliometric analysis, systematic literature review and a Delphi consensus process with equal involvement of professional and patient representatives, five recommendations are now issued. First, the term ‘Sjögren disease’ should replace ‘Sjögren syndrome’. Second, the acronym ‘SjD’ should be used as an abbreviation for ‘Sjögren disease’. Third, the descriptor ‘associated’ should be used in lieu of ‘secondary’ for Sjögren disease occurring in association with a second systemic autoimmune disease for which classification criteria are fulfilled. Fourth, Sjögren disease is the preferred terminology in common parlance and in clinical diagnosis, without differentiation as to primary and associated forms. Fifth, the differentiation between primary and associated Sjögren is recommended for scientific studies to define a homogeneous population. In conclusion, the consensus endorses ‘Sjögren disease’ as the official nomenclature to acknowledge the distinct pathogenesis of this disorder and to improve clarity in both clinical practice and research. In this Consensus Statement, an international group of experts and patient representatives validates and endorses the transition from the term ‘Sjögren syndrome’ to ‘Sjögren disease’, and issue several additional recommendations regarding the nomenclature of this disorder.
{"title":"2023 International Rome consensus for the nomenclature of Sjögren disease","authors":"Manuel Ramos-Casals, Alan N. Baer, María del Pilar Brito-Zerón, Katherine M. Hammitt, Coralie Bouillot, Soledad Retamozo, Alison Mackey, David Yarowsky, Breck Turner, Jaime Blanck, Benjamin A. Fisher, Esen K. Akpek, Chiara Baldini, Hendrika Bootsma, Simon J. Bowman, Thomas Dörner, Leslie Laing, Scott M. Lieberman, Xavier Mariette, Stephen C. Pflugfelder, Vidya Sankar, Antoni Sisó-Almirall, Athanasios G. Tzioufas, Juan-Manuel Anaya, Berkan Armağan, Michele Bombardieri, Steven Carsons, Salvatore de Vita, Robert I. Fox, Roberto Gerli, Roberto Giacomelli, Jacques Eric Gottenberg, Gabriela Hernández-Molina, Roland Jonsson, Aike Kruize, Seung-Ki Kwok, Xiaomei Li, Sara S. McCoy, Wan-Fai Ng, Peter Olsson, Maureen Rischmueller, Alain Saraux, R. Hal Scofield, Valéria Valim, Claudio Vitali, Frederick Vivino, Marie Wahren-Herlenius, Haralampos M. Moutsopoulos, on behalf of the International Task Force on Nomenclature of Sjögren Disease","doi":"10.1038/s41584-025-01268-z","DOIUrl":"10.1038/s41584-025-01268-z","url":null,"abstract":"Nomenclature for the disease widely known as Sjögren syndrome has proven unsatisfactory. Patients have perceived ‘syndrome’ as indicative of a vague collection of symptoms, prompting the Sjögren’s Foundation to abandon the term. Furthermore, the traditional distinction between ‘primary’ and ‘secondary’ forms fails to account for the complex interplay between overlapping autoimmune diseases. Following a bibliometric analysis, systematic literature review and a Delphi consensus process with equal involvement of professional and patient representatives, five recommendations are now issued. First, the term ‘Sjögren disease’ should replace ‘Sjögren syndrome’. Second, the acronym ‘SjD’ should be used as an abbreviation for ‘Sjögren disease’. Third, the descriptor ‘associated’ should be used in lieu of ‘secondary’ for Sjögren disease occurring in association with a second systemic autoimmune disease for which classification criteria are fulfilled. Fourth, Sjögren disease is the preferred terminology in common parlance and in clinical diagnosis, without differentiation as to primary and associated forms. Fifth, the differentiation between primary and associated Sjögren is recommended for scientific studies to define a homogeneous population. In conclusion, the consensus endorses ‘Sjögren disease’ as the official nomenclature to acknowledge the distinct pathogenesis of this disorder and to improve clarity in both clinical practice and research. In this Consensus Statement, an international group of experts and patient representatives validates and endorses the transition from the term ‘Sjögren syndrome’ to ‘Sjögren disease’, and issue several additional recommendations regarding the nomenclature of this disorder.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"426-437"},"PeriodicalIF":32.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41584-025-01268-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-10DOI: 10.1038/s41584-025-01274-1
Sarah Onuora
In the MESKO clinical trial, treatment with low-dose methotrexate did not improve pain or joint inflammation in individuals with inflammatory knee osteoarthritis.
在MESKO临床试验中，低剂量甲氨蝶呤治疗并没有改善炎症性膝骨关节炎患者的疼痛或关节炎症。
{"title":"Methotrexate does not improve knee OA","authors":"Sarah Onuora","doi":"10.1038/s41584-025-01274-1","DOIUrl":"10.1038/s41584-025-01274-1","url":null,"abstract":"In the MESKO clinical trial, treatment with low-dose methotrexate did not improve pain or joint inflammation in individuals with inflammatory knee osteoarthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"374-374"},"PeriodicalIF":32.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252698","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 : 2025-06-10DOI: 10.1038/s41584-025-01273-2
Sarah Onuora
The results of a new clinical trial suggest that methotrexate could be an alternative to prednisone as first-line treatment for pulmonary sarcoidosis.
一项新的临床试验结果表明，甲氨蝶呤可以替代强的松作为肺结节病的一线治疗。
{"title":"Methotrexate as first-line therapy for pulmonary sarcoidosis","authors":"Sarah Onuora","doi":"10.1038/s41584-025-01273-2","DOIUrl":"10.1038/s41584-025-01273-2","url":null,"abstract":"The results of a new clinical trial suggest that methotrexate could be an alternative to prednisone as first-line treatment for pulmonary sarcoidosis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"373-373"},"PeriodicalIF":32.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252699","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 : 2025-06-06DOI: 10.1038/s41584-025-01270-5
Samuel J. Magaziner, David B. Beck
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 arising in hematopoietic stem cells, resulting in systemic autoinflammation and clonal outgrowth of these mutant cells. New research provides insights into the paradoxical mechanism behind this clonal hematopoietic dominance.
{"title":"Clonal dominance: mutations in VEXAS syndrome take advantage of inflammation","authors":"Samuel J. Magaziner, David B. Beck","doi":"10.1038/s41584-025-01270-5","DOIUrl":"10.1038/s41584-025-01270-5","url":null,"abstract":"VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 arising in hematopoietic stem cells, resulting in systemic autoinflammation and clonal outgrowth of these mutant cells. New research provides insights into the paradoxical mechanism behind this clonal hematopoietic dominance.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"511-512"},"PeriodicalIF":32.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228982","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 : 2025-06-05DOI: 10.1038/s41584-025-01266-1
Giorgio Trivioli, Marta Casal Moura, Andreas Kronbichler, Rona M. Smith, Benjamin Terrier, Stephen McAdoo, Rachel B. Jones, Peter A. Merkel, David R. W. Jayne
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) consists of a group of small-vessel vasculitides that often present with organ-threatening or life-threatening manifestations. Current immunosuppressive treatments have improved survival and rates of remission, but are not curative, have frequent toxicities, and do not effectively prevent relapse. Clinical trials have established the role of rituximab, an anti-CD20 B cell-depleting monoclonal antibody, in both the remission-induction and maintenance phases of the disease and demonstrated that glucocorticoid doses can be substantially reduced from historical dosing levels without affecting treatment efficacy. Therapies that have the potential to be more effective and safer have become available or are under investigation. Avacopan, an oral C5a receptor antagonist, was approved as an adjunctive treatment for AAV and use of this drug in combination with rituximab or cyclophosphamide and markedly reduced glucocorticoid dosing demonstrated superior efficacy and potentially greater kidney recovery than prior standard of care. Other agents under study for treatment of AAV include next-generation anti-CD20 monoclonal antibodies, anti-CD19 chimeric antigen receptor T cells, novel complement inhibitors and agents that can target fibrosis. Alongside traditional randomized controlled trials with clinical endpoints, experimental medicine studies are focusing on mechanistic endpoints and disease biomarkers. This Review discusses current treatments and the advances in the management of AAV. This Review discusses the advances and challenges of managing antineutrophil cytoplasmic antibody-associated vasculitis. The authors discuss current treatment options, emerging therapies and unmet needs in the management of this disease.
{"title":"Advances in the treatment of ANCA-associated vasculitis","authors":"Giorgio Trivioli, Marta Casal Moura, Andreas Kronbichler, Rona M. Smith, Benjamin Terrier, Stephen McAdoo, Rachel B. Jones, Peter A. Merkel, David R. W. Jayne","doi":"10.1038/s41584-025-01266-1","DOIUrl":"10.1038/s41584-025-01266-1","url":null,"abstract":"Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) consists of a group of small-vessel vasculitides that often present with organ-threatening or life-threatening manifestations. Current immunosuppressive treatments have improved survival and rates of remission, but are not curative, have frequent toxicities, and do not effectively prevent relapse. Clinical trials have established the role of rituximab, an anti-CD20 B cell-depleting monoclonal antibody, in both the remission-induction and maintenance phases of the disease and demonstrated that glucocorticoid doses can be substantially reduced from historical dosing levels without affecting treatment efficacy. Therapies that have the potential to be more effective and safer have become available or are under investigation. Avacopan, an oral C5a receptor antagonist, was approved as an adjunctive treatment for AAV and use of this drug in combination with rituximab or cyclophosphamide and markedly reduced glucocorticoid dosing demonstrated superior efficacy and potentially greater kidney recovery than prior standard of care. Other agents under study for treatment of AAV include next-generation anti-CD20 monoclonal antibodies, anti-CD19 chimeric antigen receptor T cells, novel complement inhibitors and agents that can target fibrosis. Alongside traditional randomized controlled trials with clinical endpoints, experimental medicine studies are focusing on mechanistic endpoints and disease biomarkers. This Review discusses current treatments and the advances in the management of AAV. This Review discusses the advances and challenges of managing antineutrophil cytoplasmic antibody-associated vasculitis. The authors discuss current treatment options, emerging therapies and unmet needs in the management of this disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"396-413"},"PeriodicalIF":32.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218936","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 : 2025-05-28DOI: 10.1038/s41584-025-01269-y
Holly Webster
Two complimentary studies provide a deeper understanding of Lyme disease and the associated chronic complications, such as Lyme arthritis.
两项互补研究提供了对莱姆病及其相关慢性并发症（如莱姆病关节炎）的更深入了解。
{"title":"Insights into Lyme arthritis","authors":"Holly Webster","doi":"10.1038/s41584-025-01269-y","DOIUrl":"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":"21 7","pages":"374-374"},"PeriodicalIF":32.7,"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}
Pub Date : 2025-05-16DOI: 10.1038/s41584-025-01263-4
Vibeke Strand
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.
深静脉血栓形成和肺栓塞发生率的增加在类风湿关节炎中早已被注意到，并被归因于慢性炎症和疾病活动的影响，以及特定的生物dmard和JAK抑制剂。在ACR Open Rheumatology上，Zavoriti和Miossec的报告提供了可能解释JAK抑制剂tofacitinib的血栓前作用的数据。
{"title":"How JAK inhibitors tip the prothrombotic balance in rheumatoid arthritis","authors":"Vibeke Strand","doi":"10.1038/s41584-025-01263-4","DOIUrl":"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":"21 8","pages":"443-444"},"PeriodicalIF":32.7,"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}
Pub Date : 2025-05-14DOI: 10.1038/s41584-025-01259-0
Angela E. Zou, Suppawat Kongthong, Alisa A. Mueller, Michael B. Brenner
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. This Review provides a comprehensive overview of fibroblast biology in rheumatoid arthritis and other chronic inflammatory diseases. The authors discuss insights into fibroblast behaviour and pathogenicity from single-cell and functional studies and describe how these findings have informed efforts to therapeutically target fibroblasts.
{"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":"10.1038/s41584-025-01259-0","url":null,"abstract":"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. This Review provides a comprehensive overview of fibroblast biology in rheumatoid arthritis and other chronic inflammatory diseases. The authors discuss insights into fibroblast behaviour and pathogenicity from single-cell and functional studies and describe how these findings have informed efforts to therapeutically target fibroblasts.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 6","pages":"336-354"},"PeriodicalIF":32.7,"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}
Pub Date : 2025-05-14DOI: 10.1038/s41584-025-01250-9
Ahmet Gül, Ivona Aksentijevich, Paul Brogan, Marco Gattorno, Peter C. Grayson, Seza Ozen
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. This Review discusses the clinical features, pathogenesis, diagnosis and management of monogenic forms of vasculitis. The authors emphasize that increased awareness of these rare diseases could aid earlier diagnosis and better, more-targeted treatment options for patients.
{"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":"10.1038/s41584-025-01250-9","url":null,"abstract":"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. This Review discusses the clinical features, pathogenesis, diagnosis and management of monogenic forms of vasculitis. The authors emphasize that increased awareness of these rare diseases could aid earlier diagnosis and better, more-targeted treatment options for patients.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 7","pages":"414-425"},"PeriodicalIF":32.7,"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}
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