Nature Reviews Rheumatology最新文献

{"title":"Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus","authors":"Raphaela Goldbach-Mansky, Sara Alehashemi, Adriana A. de Jesus","doi":"10.1038/s41584-024-01184-8","DOIUrl":"10.1038/s41584-024-01184-8","url":null,"abstract":"Over the past two decades, the number of genetically defined autoinflammatory interferonopathies has steadily increased. Aicardi–Goutières syndrome and proteasome-associated autoinflammatory syndromes (PRAAS, also known as CANDLE) are caused by genetic defects that impair homeostatic intracellular nucleic acid and protein processing respectively. Research into these genetic defects revealed intracellular sensors that activate type I interferon production. In SAVI and COPA syndrome, genetic defects that cause chronic activation of the dinucleotide sensor stimulator of interferon genes (STING) share features of lung inflammation and fibrosis; and selected mutations that amplify interferon-α/β receptor signalling cause central nervous system manifestations resembling Aicardi–Goutières syndrome. Research into the monogenic causes of childhood-onset systemic lupus erythematosus (SLE) demonstrates the pathogenic role of autoantibodies to particle-bound extracellular nucleic acids that distinguishes monogenic SLE from the autoinflammatory interferonopathies. This Review introduces a classification for autoinflammatory interferonopathies and discusses the divergent and shared pathomechanisms of interferon production and signalling in these diseases. Early success with drugs that block type I interferon signalling, new insights into the roles of cytoplasmic DNA or RNA sensors, pathways in type I interferon production and organ-specific pathology of the autoinflammatory interferonopathies and monogenic SLE, reveal novel drug targets that could personalize treatment approaches. This Review provides a comprehensive update on dysregulated type I interferon production and signalling in autoinflammatory interferonopathies, monogenic systemic lupus erythematosus and conditions that present with broad immune dysregulation and interferon signatures. The authors provide a classification for autoinflammatory interferonopathies based on disease mechanisms of increased type I interferon production and signalling and overlapping clinical phenotypes.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 1","pages":"22-45"},"PeriodicalIF":29.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758131","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":"Revisiting the heterogeneity of interferon-related autoimmune diseases","authors":"Guillermo Barturen, Marta E. Alarcón-Riquelme","doi":"10.1038/s41584-024-01196-4","DOIUrl":"10.1038/s41584-024-01196-4","url":null,"abstract":"The identification of shared molecular mechanisms across systemic inflammatory autoimmune diseases with overlapping clinical manifestations has prompted research into the underlying genetics that could be driving these manifestations; elucidating these genes could aid in the diagnosis, treatment and outcome prediction of these complex diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 1","pages":"7-8"},"PeriodicalIF":29.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758189","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":"DADA2 prevalence in China","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-024-01191-9","DOIUrl":"10.1038/s41584-024-01191-9","url":null,"abstract":"Analysis of exome sequencing data indicates that the prevalence of DADA2 is higher in China compared with other regions.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 1","pages":"1-1"},"PeriodicalIF":29.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758130","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":"HLA-B27 and spondyloarthritis: at the crossroads of innate and adaptive immunity","authors":"Fatemeh Navid, Liye Chen, Paul Bowness, Robert A. Colbert","doi":"10.1038/s41584-024-01189-3","DOIUrl":"https://doi.org/10.1038/s41584-024-01189-3","url":null,"abstract":"<p><i>HLA-B*27</i> confers a strong risk of developing spondyloarthritis (SpA), which includes axial SpA with or without peripheral arthritis, enthesitis, acute anterior uveitis and gastrointestinal inflammation. Although no definitive mechanism has been established to explain the role of this HLA class I protein in the pathogenesis of SpA, three main hypotheses have emerged. First is the idea that self-peptides displayed by HLA-B27 resemble microorganism-derived peptides, leading to the expansion of autoreactive CD8⁺ T cells that trigger disease. The second and third hypotheses focus on aberrant properties of HLA-B27, including its tendency to form cell-surface dimers that can activate innate killer immunoglobulin-like receptors on CD4⁺ T helper 17 cells, triggering the production of pathogenic cytokines. HLA-B27 also misfolds in the endoplasmic reticulum, which can activate the unfolded protein response, increasing IL-23 expression and thereby promoting the production of type 17 cytokines. HLA-B27 misfolding in mesenchymal stem cells has also been linked to enhanced bone formation by mesenchymal stem cell-derived osteoblasts, which could contribute to structural damage in axial SpA. In this Review we summarize prevailing ideas about the role of HLA-B27 in SpA, discuss the latest developments as well as the gaps in current knowledge, and provide recommendations for future research to address these unmet needs.</p>","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"260 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758206","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":"An update on autoantibodies in the idiopathic inflammatory myopathies","authors":"Nur Azizah Allameen,&nbsp;Ana Isabel Ramos-Lisbona,&nbsp;Lucy R. Wedderburn,&nbsp;Ingrid E. Lundberg,&nbsp;David A. Isenberg","doi":"10.1038/s41584-024-01188-4","DOIUrl":"10.1038/s41584-024-01188-4","url":null,"abstract":"Myositis-specific autoantibodies (MSAs) have become pivotal biomarkers for idiopathic inflammatory myopathies and have revolutionized understanding of the heterogeneous disease spectrum that affects both adults and children. The discovery and characterization of MSAs have substantially enhanced patient stratification based on clinical phenotype, thereby facilitating more precise diagnosis and ultimately improving management strategies. Advances in immunoassay technologies in the past 20 years have further propelled the field forward, enabling the detection of a growing repertoire of autoantibodies with high specificity and sensitivity; however, evolving research over the past decade has revealed that even within antibody-defined subsets, considerable clinical diversity exists, suggesting a broader spectrum of disease manifestations than previously acknowledged. Challenges persist, particularly among patients who are seronegative, where the failure to identify certain rare MSAs stems from the use of diverse detection methodologies and inadequate consensus-guided standardization and validation protocols. Bridging these diagnostic gaps is crucial for optimizing patient care and refining prognostic stratification in idiopathic inflammatory myopathies. This Review provides an update on autoantibodies associated with idiopathic inflammatory myopathies in both adults and children. The authors also discuss methods of autoantibody detection and the advantages and limitations of each technique.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 1","pages":"46-62"},"PeriodicalIF":29.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735856","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":"The quest for targetable pain mechanisms in 2024","authors":"Neil Basu","doi":"10.1038/s41584-024-01195-5","DOIUrl":"https://doi.org/10.1038/s41584-024-01195-5","url":null,"abstract":"Studies published in 2024 suggest that although the repurposing of established rheumatology drugs seems to deliver incremental benefits for pain management, greater benefits could be gained in the future by targeting newly discovered pain mechanisms.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696604","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":"EULAR and PReS bridge the age gap in Still’s disease","authors":"Qiongyi Hu,&nbsp;Chengde Yang","doi":"10.1038/s41584-024-01194-6","DOIUrl":"10.1038/s41584-024-01194-6","url":null,"abstract":"EULAR and the Paediatric Rheumatology European Society (PReS) now view systemic juvenile idiopathic arthritis and adult-onset Still’s disease as a single disease — Still’s disease — given their overlapping biomarkers, clinical manifestations and complications. This consensus provides valuable insights into Still’s disease diagnosis and management across age groups, and also highlights research priorities.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 1","pages":"5-6"},"PeriodicalIF":29.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696605","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":"The emergence of SLE-causing UNC93B1 variants in 2024","authors":"George C. Tsokos","doi":"10.1038/s41584-024-01192-8","DOIUrl":"https://doi.org/10.1038/s41584-024-01192-8","url":null,"abstract":"During the past year, four studies have reported ten mutations in UNC93B1, which encodes the Toll-like receptor (TLR) chaperone protein UNC93B1. All variants increased TLR7 and TLR8 signalling and caused systemic lupus erythematosus in young individuals, and highlight the therapeutic potential of targeting TLR7 and TLR8 in this disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"168 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665369","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":"Publisher Correction: Recent advances in the diagnosis and management of neuropsychiatric lupus","authors":"Alexandra C. Legge,&nbsp;John G. Hanly","doi":"10.1038/s41584-024-01193-7","DOIUrl":"10.1038/s41584-024-01193-7","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 1","pages":"63-63"},"PeriodicalIF":29.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41584-024-01193-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601294","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}

{"title":"The essential roles of memory B cells in the pathogenesis of systemic lupus erythematosus","authors":"Thomas Dörner,&nbsp;Peter E. Lipsky","doi":"10.1038/s41584-024-01179-5","DOIUrl":"10.1038/s41584-024-01179-5","url":null,"abstract":"Emerging evidence indicates that memory B cells are dysfunctional in systemic lupus erythematosus (SLE). They are hyporesponsive to signalling through the B cell receptor (BCR) but retain responsiveness to Toll-like receptor (TLR) and type I interferon signalling, as well as to T cell-mediated activation via CD40–CD154. Chronic exposure to immune complexes of ribonucleoprotein (RNP)-specific autoantibodies and TLR-engaging or BCR-engaging cargo is likely to contribute to this partially anergic phenotype. TLR7 or TLR8 signalling and the resulting production of type I interferon, as well as the sustained activation by bystander T cells, fuel a positive feedforward loop in memory B cells that can evade negative selection and permit preferential expansion of anti-RNP autoantibodies. Clinical trials of autologous stem cell transplantation or of B cell-targeted monoclonal antibodies and chimeric antigen receptor (CAR) T cells have correlated replenishment of the memory B cell population with relapse of SLE. Moreover, the BCR hyporesponsiveness of memory B cells might explain the failure of non-depleting B cell-targeting approaches in SLE, including BTK inhibitors and anti-CD22 monoclonal antibodies. Thus, targeting of dysfunctional memory B cells might prove effective in SLE, while also avoiding the adverse events of broad-spectrum targeting of B cell&nbsp;and plasma cell subsets that are not directly involved in disease pathogenesis. BCR-independent memory B cell reactivation via TLR7 or TLR8 activation, type I interferon production, immune complex formation and T helper cell signalling is central in SLE pathogenesis. Dörner and Lipsky discuss the potential of targeting these pathways to eliminate autoreactive memory B cells and plasma cells in SLE.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 12","pages":"770-782"},"PeriodicalIF":29.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594271","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}