Nature Reviews Rheumatology最新文献

The emergence of SLE-causing UNC93B1 variants in 2024 2024 年出现可导致系统性红斑狼疮的 UNC93B1 变体

IF 33.7 1区医学

Nature Reviews Rheumatology Pub Date : 2024-11-18 DOI: 10.1038/s41584-024-01192-8

George C. Tsokos

引用次数: 0

Somatic mutations in autoinflammatory and autoimmune disease 自身炎症和自身免疫疾病中的体细胞突变

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-10-11 DOI: 10.1038/s41584-024-01168-8

Sofia Torreggiani, Flore S. Castellan, Ivona Aksentijevich, David B. Beck

{"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":"20 11","pages":"683-698"},"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}

引用次数: 0

Epstein–Barr virus as a potentiator of autoimmune diseases 爱泼斯坦-巴氏病毒是自身免疫性疾病的增效剂

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-10-10 DOI: 10.1038/s41584-024-01167-9

William H. Robinson, Shady Younis, Zelda Z. Love, Lawrence Steinman, Tobias V. Lanz

{"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":"20 11","pages":"729-740"},"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}

引用次数: 0

JAK inhibitors improve RA pain JAK 抑制剂可改善 RA 疼痛

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-10-07 DOI: 10.1038/s41584-024-01176-8

Sarah Onuora

引用次数: 0

BiTE therapy for rheumatic diseases 风湿病的生物TE疗法

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-10-04 DOI: 10.1038/s41584-024-01175-9

Sarah Onuora

引用次数: 0

Combination therapy for Behçet uveitis 贝赫切特葡萄膜炎的联合疗法

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-10-04 DOI: 10.1038/s41584-024-01173-x

Holly Webster

引用次数: 0

Downregulation of invariant chain causes autoreactive T cell expansion 下调不变链会导致自反应 T 细胞扩增

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-10-04 DOI: 10.1038/s41584-024-01174-w

Maria Papatriantafyllou

引用次数: 0

Recent advances in the diagnosis and management of neuropsychiatric lupus 神经精神狼疮诊断和管理的最新进展

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-10-02 DOI: 10.1038/s41584-024-01163-z

Alexandra C. Legge, John G. Hanly

{"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":"20 11","pages":"712-728"},"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}

引用次数: 0

The PU.1– IL-9 axis in TH9 cells promotes RA TH9 细胞中的 PU.1- IL-9 轴促进 RA 的形成

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-25 DOI: 10.1038/s41584-024-01172-y

Holly Webster

引用次数: 0

Lupus nephritis-related chronic kidney disease 狼疮肾炎相关慢性肾病

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-09-24 DOI: 10.1038/s41584-024-01158-w

Julia Lichtnekert, Hans-Joachim Anders

{"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}

引用次数: 0