Pub Date : 2024-10-15DOI: 10.1038/s41584-024-01180-y
Maria Papatriantafyllou
Synovial fibroblasts from individuals with OA release small extracellular vesicles with potentially pathogenic miRNA cargo.
患有 OA 的滑膜成纤维细胞会释放出含有潜在致病 miRNA 的小细胞外囊泡。
{"title":"Erosive cargo from synovial fibroblasts","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-024-01180-y","DOIUrl":"https://doi.org/10.1038/s41584-024-01180-y","url":null,"abstract":"Synovial fibroblasts from individuals with OA release small extracellular vesicles with potentially pathogenic miRNA cargo.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":33.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439169","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 : 2024-10-11DOI: 10.1038/s41584-024-01168-8
Sofia Torreggiani, Flore S. Castellan, Ivona Aksentijevich, David B. Beck
Somatic mutations (also known as acquired mutations) are emerging as common, age-related processes that occur in all cells throughout the body. Somatic mutations are canonically linked to malignant processes but over the past decade have been increasingly causally connected to benign diseases including rheumatic conditions. Here we outline the contribution of somatic mutations to complex and monogenic immunological diseases with a detailed review of unique aspects associated with such causes. Somatic mutations can cause early- or late-onset rheumatic monogenic diseases but also contribute to the pathogenesis of complex inflammatory and immune-mediated diseases, affect disease progression and define new clinical subtypes. Although even variants with a low variant allele fraction can be pathogenic, clonal dynamics could lead to changes over time in the proportion of mutant cells, with possible phenotypic consequences for the individual. Thus, somatic mutagenesis and clonal expansion have relevant implications in genetic testing and counselling. On the basis of both increased recognition of somatic diseases in clinical practice and improved technical and bioinformatic processes, we hypothesize that there will be an ever-expanding list of somatic mutations in various genes leading to inflammatory conditions, particularly in late-onset disease. This Review discusses the involvement of early-stage and late-stage somatic mutations in the pathogenesis of both monogenic and multifactorial rheumatic diseases. The authors highlight new methods of detecting low-frequency variants and the implications for diagnosis and treatment in patients with rheumatic diseases.
{"title":"Somatic mutations in autoinflammatory and autoimmune disease","authors":"Sofia Torreggiani, Flore S. Castellan, Ivona Aksentijevich, David B. Beck","doi":"10.1038/s41584-024-01168-8","DOIUrl":"10.1038/s41584-024-01168-8","url":null,"abstract":"Somatic mutations (also known as acquired mutations) are emerging as common, age-related processes that occur in all cells throughout the body. Somatic mutations are canonically linked to malignant processes but over the past decade have been increasingly causally connected to benign diseases including rheumatic conditions. Here we outline the contribution of somatic mutations to complex and monogenic immunological diseases with a detailed review of unique aspects associated with such causes. Somatic mutations can cause early- or late-onset rheumatic monogenic diseases but also contribute to the pathogenesis of complex inflammatory and immune-mediated diseases, affect disease progression and define new clinical subtypes. Although even variants with a low variant allele fraction can be pathogenic, clonal dynamics could lead to changes over time in the proportion of mutant cells, with possible phenotypic consequences for the individual. Thus, somatic mutagenesis and clonal expansion have relevant implications in genetic testing and counselling. On the basis of both increased recognition of somatic diseases in clinical practice and improved technical and bioinformatic processes, we hypothesize that there will be an ever-expanding list of somatic mutations in various genes leading to inflammatory conditions, particularly in late-onset disease. This Review discusses the involvement of early-stage and late-stage somatic mutations in the pathogenesis of both monogenic and multifactorial rheumatic diseases. The authors highlight new methods of detecting low-frequency variants and the implications for diagnosis and treatment in patients with rheumatic diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405575","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 : 2024-10-10DOI: 10.1038/s41584-024-01167-9
William H. Robinson, Shady Younis, Zelda Z. Love, Lawrence Steinman, Tobias V. Lanz
The Epstein–Barr virus (EBV) is epidemiologically associated with development of autoimmune diseases, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. Although there is well-established evidence for this association, the underlying mechanistic basis remains incompletely defined. In this Review, we discuss the role of EBV infection as a potentiator of autoimmune rheumatic diseases. We review the EBV life cycle, viral transcription programmes, serological profiles and lytic reactivation. We discuss the epidemiological and mechanistic associations of EBV with systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. We describe the potential mechanisms by which EBV might promote autoimmunity, including EBV nuclear antigen 1-mediated molecular mimicry of human autoantigens; EBV-mediated B cell reprogramming, including EBV nuclear antigen 2-mediated dysregulation of autoimmune susceptibility genes; EBV and host genetic factors, including the potential for autoimmunity-promoting strains of EBV; EBV immune evasion and insufficient host responses to control infection; lytic reactivation; and other mechanisms. Finally, we discuss the therapeutic implications and potential therapeutic approaches to targeting EBV for the treatment of autoimmune disease. Epstein–Barr virus (EBV) infection is associated with numerous autoimmune diseases, including rheumatic diseases. In this Review, Robinson and colleagues provide an overview of the biology of EBV, the potential mechanisms through which EBV could promote autoimmune diseases and how EBV might be targeted for the treatment of autoimmune disease.
{"title":"Epstein–Barr virus as a potentiator of autoimmune diseases","authors":"William H. Robinson, Shady Younis, Zelda Z. Love, Lawrence Steinman, Tobias V. Lanz","doi":"10.1038/s41584-024-01167-9","DOIUrl":"10.1038/s41584-024-01167-9","url":null,"abstract":"The Epstein–Barr virus (EBV) is epidemiologically associated with development of autoimmune diseases, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. Although there is well-established evidence for this association, the underlying mechanistic basis remains incompletely defined. In this Review, we discuss the role of EBV infection as a potentiator of autoimmune rheumatic diseases. We review the EBV life cycle, viral transcription programmes, serological profiles and lytic reactivation. We discuss the epidemiological and mechanistic associations of EBV with systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. We describe the potential mechanisms by which EBV might promote autoimmunity, including EBV nuclear antigen 1-mediated molecular mimicry of human autoantigens; EBV-mediated B cell reprogramming, including EBV nuclear antigen 2-mediated dysregulation of autoimmune susceptibility genes; EBV and host genetic factors, including the potential for autoimmunity-promoting strains of EBV; EBV immune evasion and insufficient host responses to control infection; lytic reactivation; and other mechanisms. Finally, we discuss the therapeutic implications and potential therapeutic approaches to targeting EBV for the treatment of autoimmune disease. Epstein–Barr virus (EBV) infection is associated with numerous autoimmune diseases, including rheumatic diseases. In this Review, Robinson and colleagues provide an overview of the biology of EBV, the potential mechanisms through which EBV could promote autoimmune diseases and how EBV might be targeted for the treatment of autoimmune disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397832","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 : 2024-10-07DOI: 10.1038/s41584-024-01176-8
Sarah Onuora
Consistent with findings from clinical trials, in a retrospective cohort study, Janus kinase inhibitors improved pain associated with rheumatoid arthritis as well as or better than biologic DMARDs in clinical practice.
{"title":"JAK inhibitors improve RA pain","authors":"Sarah Onuora","doi":"10.1038/s41584-024-01176-8","DOIUrl":"10.1038/s41584-024-01176-8","url":null,"abstract":"Consistent with findings from clinical trials, in a retrospective cohort study, Janus kinase inhibitors improved pain associated with rheumatoid arthritis as well as or better than biologic DMARDs in clinical practice.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383612","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 : 2024-10-04DOI: 10.1038/s41584-024-01175-9
Sarah Onuora
The bispecific T cell engager antibody teclistamab has now been used to successfully treat five patients with treatment-resistant autoimmune rheumatic diseases.
目前，双特异性 T 细胞吞噬抗体 teclistamab 已成功用于治疗五名患有耐药性自身免疫性风湿病的患者。
{"title":"BiTE therapy for rheumatic diseases","authors":"Sarah Onuora","doi":"10.1038/s41584-024-01175-9","DOIUrl":"10.1038/s41584-024-01175-9","url":null,"abstract":"The bispecific T cell engager antibody teclistamab has now been used to successfully treat five patients with treatment-resistant autoimmune rheumatic diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374235","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 : 2024-10-04DOI: 10.1038/s41584-024-01173-x
Holly Webster
A study has compared the safety and efficacy of three different immunomodulatory drugs combined with glucocorticoids for the treatment of Behçet uveitis.
一项研究比较了三种不同的免疫调节药物联合糖皮质激素治疗贝赫切特葡萄膜炎的安全性和有效性。
{"title":"Combination therapy for Behçet uveitis","authors":"Holly Webster","doi":"10.1038/s41584-024-01173-x","DOIUrl":"10.1038/s41584-024-01173-x","url":null,"abstract":"A study has compared the safety and efficacy of three different immunomodulatory drugs combined with glucocorticoids for the treatment of Behçet uveitis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374236","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 : 2024-10-04DOI: 10.1038/s41584-024-01174-w
Maria Papatriantafyllou
Neoself-antigens presented by MHC-II molecules in the absence of invariant chain drive clonal expansion of autoreactive T cells in SLE.
在缺乏不变链的情况下，由 MHC-II 分子呈现的新自身抗原会驱动系统性红斑狼疮患者自身反应性 T 细胞的克隆扩增。
{"title":"Downregulation of invariant chain causes autoreactive T cell expansion","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-024-01174-w","DOIUrl":"10.1038/s41584-024-01174-w","url":null,"abstract":"Neoself-antigens presented by MHC-II molecules in the absence of invariant chain drive clonal expansion of autoreactive T cells in SLE.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374234","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 : 2024-10-02DOI: 10.1038/s41584-024-01163-z
Alexandra C. Legge, John G. Hanly
Neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are common and frequently associated with a substantial negative impact on health outcomes. The pathogenesis of neuropsychiatric SLE (NPSLE) remains largely unknown, but a single pathogenic mechanism is unlikely to be responsible for the heterogeneous array of clinical manifestations, and a combination of inflammatory and ischaemic mechanistic pathways have been implicated. Currently, valid and reliable biomarkers for the diagnosis of NPSLE are lacking, and differentiating NPSLE from nervous system dysfunction not caused by SLE remains a major challenge for clinicians. However, correct attribution is essential to ensure timely institution of appropriate treatment. In the absence of randomized clinical trials on NPSLE, current treatment strategies are derived from clinical experience with different therapeutic modalities and their efficacy in the management of other manifestations of SLE or of neuropsychiatric disease in non-SLE populations. This Review describes recent advances in the understanding of NPSLE that can inform diagnosis and management, as well as unanswered questions that necessitate further research. Neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are common and negatively impact health. Diagnosing neuropsychiatric SLE is challenging owing to a lack of reliable biomarkers, and current treatments rely on clinical experience. This Review covers recent clinical advances in this area and emphasizes the need for further research.
{"title":"Recent advances in the diagnosis and management of neuropsychiatric lupus","authors":"Alexandra C. Legge, John G. Hanly","doi":"10.1038/s41584-024-01163-z","DOIUrl":"10.1038/s41584-024-01163-z","url":null,"abstract":"Neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are common and frequently associated with a substantial negative impact on health outcomes. The pathogenesis of neuropsychiatric SLE (NPSLE) remains largely unknown, but a single pathogenic mechanism is unlikely to be responsible for the heterogeneous array of clinical manifestations, and a combination of inflammatory and ischaemic mechanistic pathways have been implicated. Currently, valid and reliable biomarkers for the diagnosis of NPSLE are lacking, and differentiating NPSLE from nervous system dysfunction not caused by SLE remains a major challenge for clinicians. However, correct attribution is essential to ensure timely institution of appropriate treatment. In the absence of randomized clinical trials on NPSLE, current treatment strategies are derived from clinical experience with different therapeutic modalities and their efficacy in the management of other manifestations of SLE or of neuropsychiatric disease in non-SLE populations. This Review describes recent advances in the understanding of NPSLE that can inform diagnosis and management, as well as unanswered questions that necessitate further research. Neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are common and negatively impact health. Diagnosing neuropsychiatric SLE is challenging owing to a lack of reliable biomarkers, and current treatments rely on clinical experience. This Review covers recent clinical advances in this area and emphasizes the need for further research.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363004","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 : 2024-09-26DOI: 10.1038/s41584-024-01170-0
Denis Poddubnyy
New classification criteria for axial disease in juvenile spondyloarthritis aim to enhance the identification and study of this condition in affected youth, offering a tool for future non-interventional studies and interventional trials. Better understanding of the efficacy of various interventions in the axial domain could help tailor treatment strategies.
{"title":"Defining axial involvement in juvenile SpA","authors":"Denis Poddubnyy","doi":"10.1038/s41584-024-01170-0","DOIUrl":"https://doi.org/10.1038/s41584-024-01170-0","url":null,"abstract":"New classification criteria for axial disease in juvenile spondyloarthritis aim to enhance the identification and study of this condition in affected youth, offering a tool for future non-interventional studies and interventional trials. Better understanding of the efficacy of various interventions in the axial domain could help tailor treatment strategies.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":33.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321388","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 : 2024-09-25DOI: 10.1038/s41584-024-01172-y
Holly Webster
Findings show a role for the PU.1–IL-9 axis in TH9 cells in the pathogenesis of RA.
研究结果表明，TH9 细胞中的 PU.1-IL-9 轴在 RA 的发病机制中发挥作用。
{"title":"The PU.1– IL-9 axis in TH9 cells promotes RA","authors":"Holly Webster","doi":"10.1038/s41584-024-01172-y","DOIUrl":"10.1038/s41584-024-01172-y","url":null,"abstract":"Findings show a role for the PU.1–IL-9 axis in TH9 cells in the pathogenesis of RA.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":29.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317015","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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