Nature Reviews Rheumatology最新文献

JAK inhibitor selectivity: new opportunities, better drugs? JAK 抑制剂的选择性：新机遇，更好的药物？

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-09 DOI: 10.1038/s41584-024-01153-1

Anniina Virtanen, Francesca Romana Spinelli, Jean Baptiste Telliez, John J. O’Shea, Olli Silvennoinen, Massimo Gadina

{"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":"https://doi.org/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.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":33.7,"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}

引用次数: 0

Interferon disrupts immune and tissue homeostasis in SLE via CXCL13 干扰素通过 CXCL13 破坏系统性红斑狼疮的免疫和组织稳态

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-09 DOI: 10.1038/s41584-024-01164-y

Mehrdad Pazhouhandeh, Di Yu

引用次数: 0

Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis 作为类风湿性关节炎诱因和驱动因素的不同粘膜内型

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-09 DOI: 10.1038/s41584-024-01154-0

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

{"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":"https://doi.org/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.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":33.7,"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}

引用次数: 0

An interdisciplinary perspective on peripheral drivers of pain in rheumatoid arthritis 从跨学科角度看类风湿性关节炎疼痛的外周驱动因素

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-06 DOI: 10.1038/s41584-024-01155-z

Zoe Rutter-Locher, Bruce W. Kirkham, Kirsty Bannister, David L. Bennett, Christopher D. Buckley, Leonie S. Taams, Franziska Denk

引用次数: 0

Molecular mimicry links SARS-CoV-2 infection and MIS-C. 分子模拟将 SARS-CoV-2 感染与 MIS-C 联系起来。

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-05 DOI: 10.1038/s41584-024-01166-w

Jessica McHugh

引用次数: 0

Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy 系统性红斑狼疮遗传学：对发病机制的认识和对治疗的影响

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-04 DOI: 10.1038/s41584-024-01152-2

Yogita Ghodke-Puranik, Mikhail Olferiev, Mary K. Crow

{"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":"https://doi.org/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.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":null,"pages":null},"PeriodicalIF":33.7,"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}

引用次数: 0

Helicobacter pylori-induced citrullination linked to RA exacerbation 幽门螺杆菌诱导的瓜氨酸化与 RA 恶化有关

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-04 DOI: 10.1038/s41584-024-01165-x

Holly Webster

引用次数: 0

Guiding ILD management in systemic autoimmune rheumatic diseases 指导系统性自身免疫性风湿病的 ILD 管理

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-04 DOI: 10.1038/s41584-024-01160-2

Fabrizio Luppi, Marco Sebastiani

引用次数: 0

Is X chromosome inactivation a cause or effect of SLE? X 染色体失活是系统性红斑狼疮的原因还是结果？

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-02 DOI: 10.1038/s41584-024-01159-9

R Hal Scofield, Valerie M Lewis

引用次数: 0

The immune health metric as an indicator of health and disease 作为健康和疾病指标的免疫健康指标

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-02 DOI: 10.1038/s41584-024-01162-0

Satoshi Kubo, Yoshiya Tanaka

引用次数: 0