Nature Reviews Rheumatology最新文献

{"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":"17 1","pages":""},"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}

{"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":"20 11","pages":"667-667"},"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}

{"title":"Lupus nephritis-related chronic kidney disease","authors":"Julia Lichtnekert, Hans-Joachim Anders","doi":"10.1038/s41584-024-01158-w","DOIUrl":"10.1038/s41584-024-01158-w","url":null,"abstract":"Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) and a determinant of overall morbidity and mortality, as lupus nephritis-related chronic kidney disease (CKD) drives cardiovascular disease and secondary immunodeficiency. Two lines of action are required to prevent the progression of lupus nephritis-related CKD: suppression of autoimmune SLE activity, which is a risk factor for immunopathology-related irreversible kidney injury, and management of non-immune risk factors that contribute to CKD progression. As each episode or relapse of active lupus nephritis implicates CKD progression, preventing flares of lupus nephritis is a key treatment target. Non-immune risk factors of CKD mostly include causes of nephron hyperfiltration, such as obesity, hypertension, sodium- or protein-rich diets and type 2 diabetes mellitus, as well as pregnancy. Nephrotoxic agents and smoking also drive kidney cell loss. Intrinsic risk factors for CKD progression include poor nephron endowment because of prematurity at birth, nephropathic genetic variants, ageing, male sex and previous or concomitant kidney diseases. Care for lupus nephritis involves the control of all modifiable risk factors of CKD progression. In addition, remnant nephron overload can be reduced using early dual therapy with inhibitors of the renin–angiotensin system and sodium–glucose transporter-2, whereas further renoprotective drug interventions are underway. As patients with lupus nephritis are at risk of CKD progression, they would all benefit from interdisciplinary care to minimize the risk of kidney failure, cardiovascular disease and infections. Each episode of lupus nephritis causes irreversible kidney injury, initiating and, subsequently, exacerbating chronic kidney disease. This Review discusses how interdisciplinary care that considers all immune and non-immune risk factors for chronic kidney disease progression can benefit patients with lupus nephritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 11","pages":"699-711"},"PeriodicalIF":29.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313873","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: Integrin signalling in joint development, homeostasis and osteoarthritis","authors":"Michael Z. Miao, Janice S. Lee, Kenneth M. Yamada, Richard F. Loeser","doi":"10.1038/s41584-024-01171-z","DOIUrl":"10.1038/s41584-024-01171-z","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 12","pages":"809-809"},"PeriodicalIF":29.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41584-024-01171-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275336","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":"JAK inhibitor selectivity: new opportunities, better drugs?","authors":"Anniina Virtanen, Francesca Romana Spinelli, Jean Baptiste Telliez, John J. O’Shea, Olli Silvennoinen, Massimo Gadina","doi":"10.1038/s41584-024-01153-1","DOIUrl":"10.1038/s41584-024-01153-1","url":null,"abstract":"Cytokines function as communication tools of the immune system, serving critical functions in many biological responses and shaping the immune response. When cytokine production or their biological activity goes awry, the homeostatic balance of the immune response is altered, leading to the development of several pathologies such as autoimmune and inflammatory disorders. Cytokines bind to specific receptors on cells, triggering the activation of intracellular enzymes known as Janus kinases (JAKs). The JAK family comprises four members, JAK1, JAK2, JAK3 and tyrosine kinase 2, which are critical for intracellular cytokine signalling. Since the mid-2010s multiple JAK inhibitors have been approved for inflammatory and haematological indications. Currently, approved JAK inhibitors have demonstrated clinical efficacy; however, improved selectivity for specific JAKs is likely to enhance safety profiles, and different strategies have been used to accomplish enhanced JAK selectivity. In this update, we discuss the background of JAK inhibitors, current approved indications and adverse effects, along with new developments in this field. We address the issue of JAK selectivity and its relevance in terms of efficacy, and describe new modalities of JAK targeting, as well as new aspects of JAK inhibitor action. This Review provides an update on developments in Janus kinase inhibitors, including new disease indications and adverse effects. The authors discuss issues surrounding selectivity and efficacy, as well as new routes for administration of Janus kinase inhibitors.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"649-665"},"PeriodicalIF":29.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158951","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":"Interferon disrupts immune and tissue homeostasis in SLE via CXCL13","authors":"Mehrdad Pazhouhandeh, Di Yu","doi":"10.1038/s41584-024-01164-y","DOIUrl":"10.1038/s41584-024-01164-y","url":null,"abstract":"Type I interferon has a crucial role in the immunopathogenesis of systemic lupus erythematosus (SLE). Analysis of CD4+ T cells from individuals with SLE now shows that type I interferon intervenes with the transcriptional regulators AHR and JUN to downregulate expression of IL-22, which promotes tissue regeneration, and upregulate the expression of CXCL13, which supports lymphoid structure formation.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 12","pages":"745-746"},"PeriodicalIF":29.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158950","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":"Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis","authors":"V. Michael Holers, Kristen M. Demoruelle, Jane H. Buckner, Eddie A. James, Gary S. Firestein, William H. Robinson, Allen C. Steere, Fan Zhang, Jill M. Norris, Kristine A. Kuhn, Kevin D. Deane","doi":"10.1038/s41584-024-01154-0","DOIUrl":"10.1038/s41584-024-01154-0","url":null,"abstract":"Rheumatoid arthritis (RA) is a potentially devastating autoimmune disease. The great majority of patients with RA are seropositive for anti-citrullinated protein antibodies (ACPAs), rheumatoid factors, or other autoantibodies. The onset of clinically apparent inflammatory arthritis meeting classification criteria (clinical RA) is preceded by ACPA seropositivity for an average of 3–5 years, a period that is designated as ‘at-risk’ of RA for ACPA-positive individuals who do not display signs of arthritis, or ‘pre-RA’ for individuals who are known to have progressed to developing clinical RA. Prior studies of individuals at-risk of RA have associated pulmonary mucosal inflammation with local production of ACPAs and rheumatoid factors, leading to development of the ‘mucosal origins hypothesis’. Recent work now suggests the presence of multiple distinct mucosal site-specific mechanisms that drive RA evolution. Indicatively, subsets of individuals at-risk of RA and patients with RA harbour a faecal bacterial strain that has exhibited arthritogenic activity in animal models and that favours T helper 17 (TH17) cell responses in patients. Periodontal inflammation and oral microbiota have also been suggested to promote the development of arthritis through breaches in the mucosal barrier. Herein, we argue that mucosal sites and their associated microbial strains can contribute to RA evolution via distinct pathogenic mechanisms, which can be considered causal mucosal endotypes. Future therapies instituted for prevention in the at-risk period, or, perhaps, during clinical RA as therapeutics for active arthritis, will possibly have to address these individual mechanisms as part of precision medicine approaches. Holers and colleagues review current data linking immune mechanisms and dysbiosis at distinct mucosal sites to risk of rheumatoid arthritis (RA). Their newly introduced causal mucosal endotypes hypothesis suggests that lung-, gut-, or oral-associated endotypes might drive the pathogenesis and progression of RA, and highlights associated research directions towards preventive and therapeutic strategies in RA.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"601-613"},"PeriodicalIF":29.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160712","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 interdisciplinary perspective on peripheral drivers of pain in rheumatoid arthritis","authors":"Zoe Rutter-Locher, Bruce W. Kirkham, Kirsty Bannister, David L. Bennett, Christopher D. Buckley, Leonie S. Taams, Franziska Denk","doi":"10.1038/s41584-024-01155-z","DOIUrl":"10.1038/s41584-024-01155-z","url":null,"abstract":"Pain is one of the most debilitating symptoms of rheumatoid arthritis (RA), and yet remains poorly understood, especially when pain occurs in the absence of synovitis. Without active inflammation, experts most often attribute joint pain to central nervous system dysfunction. However, advances in the past 5 years in both immunology and neuroscience research suggest that chronic pain in RA is also driven by a variety of abnormal interactions between peripheral neurons and mediators produced by resident cells in the local joint environment. In this Review, we discuss these novel insights from an interdisciplinary neuro-immune perspective. We outline a potential working model for the peripheral drivers of pain in RA, which includes autoantibodies, resident immune and mesenchymal cells and their interactions with different subtypes of peripheral sensory neurons. We also offer suggestions for how future collaborative research could be designed to accelerate analgesic drug development. Emerging data suggest that resident cells and locally produced mediators interact with nerves in the joint to promote pain in rheumatoid arthritis. This Review discusses the potential neuro–immune–stromal interactions promoting joint pain and highlights the need for an interdisciplinary approach to therapeutic development.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 11","pages":"671-682"},"PeriodicalIF":29.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142521","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":"Molecular mimicry links SARS-CoV-2 infection and MIS-C","authors":"Jessica McHugh","doi":"10.1038/s41584-024-01166-w","DOIUrl":"10.1038/s41584-024-01166-w","url":null,"abstract":"Researchers have identified a mechanistic link between SARS-CoV-2 infection and multisystem inflammatory syndrome in children, providing evidence for the involvement of molecular mimicry.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"598-598"},"PeriodicalIF":29.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140569","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":"Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy","authors":"Yogita Ghodke-Puranik, Mikhail Olferiev, Mary K. Crow","doi":"10.1038/s41584-024-01152-2","DOIUrl":"10.1038/s41584-024-01152-2","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a prime example of how the interplay between genetic and environmental factors can trigger systemic autoimmunity, particularly in young women. Although clinical disease can take years to manifest, risk is established by the unique genetic makeup of an individual. Genome-wide association studies have identified almost 200 SLE-associated risk loci, yet unravelling the functional effect of these loci remains a challenge. New analytic tools have enabled researchers to delve deeper, leveraging DNA sequencing and cell-specific and immune pathway analysis to elucidate the immunopathogenic mechanisms. Both common genetic variants and rare non-synonymous mutations can interact to increase SLE risk. Notably, variants strongly associated with SLE are often located in genome super-enhancers that regulate MHC class II gene expression. Additionally, the 3D conformations of DNA and RNA contribute to genome regulation and innate immune system activation. Improved therapies for SLE are urgently needed and current and future knowledge from genetic and genomic research should provide new tools to facilitate patient diagnosis, enhance the identification of therapeutic targets and optimize testing of agents. This Review explores the genetic basis of systemic lupus erythematosus, including the role of enhancers in the MHC region, the 3D structure of DNA and various pathway-specific mechanisms. These findings enhance disease understanding and inform improved diagnosis and treatment strategies.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"635-648"},"PeriodicalIF":29.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130741","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}