Nature Reviews Rheumatology最新文献_第5页

The past 25 years in paediatric rheumatology: insights from monogenic diseases 过去 25 年的儿科风湿病学：单基因疾病的启示

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-08-07 DOI: 10.1038/s41584-024-01145-1

Seza Ozen, Ivona Aksentijevich

{"title":"The past 25 years in paediatric rheumatology: insights from monogenic diseases","authors":"Seza Ozen, Ivona Aksentijevich","doi":"10.1038/s41584-024-01145-1","DOIUrl":"10.1038/s41584-024-01145-1","url":null,"abstract":"The past 25 years have seen major novel developments in the field of paediatric rheumatology. The concept of autoinflammation was introduced to this field, and medicine more broadly, with studies of familial Mediterranean fever, the most common autoinflammatory disease globally. New data on the positive evolutionary selection of familial Mediterranean fever-associated genetic variants might be pertinent to mild gain-of-function variants reported in other disease-associated genes. Genetic studies have unveiled the complexity of human heritability to inflammation and flourishing data from rare monogenic disorders have contributed to a better understanding of general disease mechanisms in paediatric rheumatic conditions. Beyond genomics, the application of other ‘omics’ technologies, including transcriptomics, proteomics and metabolomics, has generated an enormous dataset that can be applied to the development of new therapies and in the practice of precision medicine. Novel biomarkers for monitoring disease activity and progression have also emerged. A surge in the development of targeted biologic therapies has led to durable remission and improved prognosis for many diseases that in the past caused major complications. Last but not least, the COVID-19 pandemic has affected paediatric rheumatology practice and has sparked new investigations into the link between viral infections and unregulated inflammatory responses in children. Paediatric rheumatology has seen many notable developments in the past 25 years, including the introduction of the concept of autoinflammation and a greater understanding of the genetics and pathogenesis of inflammatory diseases. In this Perspective, Ozen and Aksentijevich discuss how these and other discoveries have transformed the field and herald improvements in patient care.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"585-593"},"PeriodicalIF":29.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899447","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 role of obesity and adipose tissue dysfunction in osteoarthritis pain 肥胖和脂肪组织功能障碍在骨关节炎疼痛中的作用。

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-08-07 DOI: 10.1038/s41584-024-01143-3

Marie Binvignat, Jérémie Sellam, Francis Berenbaum, David T. Felson

{"title":"The role of obesity and adipose tissue dysfunction in osteoarthritis pain","authors":"Marie Binvignat, Jérémie Sellam, Francis Berenbaum, David T. Felson","doi":"10.1038/s41584-024-01143-3","DOIUrl":"10.1038/s41584-024-01143-3","url":null,"abstract":"Obesity has a pivotal and multifaceted role in pain associated with osteoarthritis (OA), extending beyond the mechanistic influence of BMI. It exerts its effects both directly and indirectly through various modifiable risk factors associated with OA-related pain. Adipose tissue dysfunction is highly involved in OA-related pain through local and systemic inflammation, immune dysfunction, and the production of pro-inflammatory cytokines and adipokines. Adipose tissue dysfunction is intricately connected with metabolic syndrome, which independently exerts specific effects on OA-related pain, distinct from its association with BMI. The interplay among obesity, adipose tissue dysfunction and metabolic syndrome influences OA-related pain through diverse pain mechanisms, including nociceptive pain, peripheral sensitization and central sensitization. These complex interactions contribute to the heightened pain experience observed in individuals with OA and obesity. In addition, pain management strategies are less efficient in individuals with obesity. Importantly, therapeutic interventions targeting obesity and metabolic syndrome hold promise in managing OA-related pain. A deeper understanding of the intricate relationship between obesity, metabolic syndrome and OA-related pain is crucial and could have important implications for improving pain management and developing innovative therapeutic options in OA. In this Review, the authors explore the complex interactions between osteoarthritis-related pain and obesity, adipose tissue dysfunction and metabolic syndrome, and discuss how knowledge of these relationships could help improve pain management and identify new therapeutic options.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"565-584"},"PeriodicalIF":29.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902409","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

Advancements and challenges in CAR T cell therapy in autoimmune diseases 自身免疫性疾病 CAR T 细胞疗法的进展与挑战

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-08-06 DOI: 10.1038/s41584-024-01139-z

Georg Schett, Fabian Müller, Jule Taubmann, Andreas Mackensen, Wei Wang, Rich A. Furie, Ralf Gold, Aiden Haghikia, Peter A. Merkel, Roberto Caricchio, Maria-Antonietta D’Agostino, Franco Locatelli, Carl H. June, Dimitrios Mougiakakos

{"title":"Advancements and challenges in CAR T cell therapy in autoimmune diseases","authors":"Georg Schett, Fabian Müller, Jule Taubmann, Andreas Mackensen, Wei Wang, Rich A. Furie, Ralf Gold, Aiden Haghikia, Peter A. Merkel, Roberto Caricchio, Maria-Antonietta D’Agostino, Franco Locatelli, Carl H. June, Dimitrios Mougiakakos","doi":"10.1038/s41584-024-01139-z","DOIUrl":"10.1038/s41584-024-01139-z","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells are highly effective at targeting and eliminating cells of the B cell lineage. CAR T cell therapy has become a standard-of-care treatment for patients with relapsed or refractory B cell malignancies. In addition, the administration of genetically modified T cells with the capacity to deplete B cells and/or plasma cells has tremendous therapeutic potential in autoimmune diseases. In the past few years, CD19-based and B cell maturation antigen (BCMA)-based CAR T cell therapies have been applied to various B cell-mediated autoimmune diseases including systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis and multiple sclerosis. The scientific rationale behind this approach is that deep depletion of B cells, including autoreactive B cell clones, could restore normal immune function, referred to as an immune reset. In this Review, we discuss important aspects of CAR T cell therapy in autoimmune disease, including considerations relating to patient selection, safety, efficacy and medical management. These considerations are based on the early experiences of CAR T cell therapy in autoimmune diseases, and as the field of CAR T cell therapy in autoimmune diseases continues to rapidly evolve, these issues will remain subject to ongoing refinement and adaptation. CAR T cell therapy shows promise for achieving long-term drug-free remission in various autoimmune diseases. This Review discusses the ongoing challenges and unanswered questions of CAR T cell therapy in autoimmune diseases, including pre-procedural, procedural and post-procedural considerations.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"531-544"},"PeriodicalIF":29.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895485","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

Shedding light onto the immunometabolic effects of glucocorticoids 揭示糖皮质激素的免疫代谢作用。

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-08-01 DOI: 10.1038/s41584-024-01144-2

Luis M. Franco

引用次数: 0

Off-the-shelf CAR T cells for refractory autoimmunity 治疗难治性自身免疫的现成 CAR T 细胞

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-07-29 DOI: 10.1038/s41584-024-01148-y

Maria Papatriantafyllou

引用次数: 0

UNC93B1 variants promote SLE via TLR activation UNC93B1 变体通过 TLR 激活促进系统性红斑狼疮的发生。

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-07-26 DOI: 10.1038/s41584-024-01147-z

Holly Webster

引用次数: 0

Integrin signalling in joint development, homeostasis and osteoarthritis 关节发育、稳态和骨关节炎中的整合素信号传递

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-07-16 DOI: 10.1038/s41584-024-01130-8

Michael Z. Miao, Janice S. Lee, Kenneth M. Yamada, Richard F. Loeser

{"title":"Integrin signalling in joint development, homeostasis and osteoarthritis","authors":"Michael Z. Miao, Janice S. Lee, Kenneth M. Yamada, Richard F. Loeser","doi":"10.1038/s41584-024-01130-8","DOIUrl":"10.1038/s41584-024-01130-8","url":null,"abstract":"Integrins are key regulators of cell–matrix interactions during joint development and joint tissue homeostasis, as well as in the development of osteoarthritis (OA). The signalling cascades initiated by the interactions of integrins with a complex network of extracellular matrix (ECM) components and intracellular adaptor proteins orchestrate cellular responses necessary for maintaining joint tissue integrity. Dysregulated integrin signalling, triggered by matrix degradation products such as matrikines, disrupts this delicate balance, tipping the scales towards an environment conducive to OA pathogenesis. The interplay between integrin signalling and growth factor pathways further underscores the multifaceted nature of OA. Moreover, emerging insights into the role of endocytic trafficking in regulating integrin signalling add a new layer of complexity to the understanding of OA development. To harness the therapeutic potential of targeting integrins for mitigation of OA, comprehensive understanding of their molecular mechanisms across joint tissues is imperative. Ultimately, deciphering the complexities of integrin signalling will advance the ability to treat OA and alleviate its global burden. Integrins are involved in joint tissue development and homeostasis, and perturbations in the availability of integrin ligands or in downstream integrin signalling are linked to the pathogenesis of osteoarthritis (OA). This Review discusses current evidence and future perspectives for therapeutically targeting integrins in OA.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"492-509"},"PeriodicalIF":29.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625031","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 pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies 痛风的发病机制：从基因、表观基因组和转录组研究中获得的分子见解。

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-07-11 DOI: 10.1038/s41584-024-01137-1

Megan P. Leask, Tania O. Crișan, Aichang Ji, Hirotaka Matsuo, Anna Köttgen, Tony R. Merriman

{"title":"The pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies","authors":"Megan P. Leask, Tania O. Crișan, Aichang Ji, Hirotaka Matsuo, Anna Köttgen, Tony R. Merriman","doi":"10.1038/s41584-024-01137-1","DOIUrl":"10.1038/s41584-024-01137-1","url":null,"abstract":"The pathogenesis of gout involves a series of steps beginning with hyperuricaemia, followed by the deposition of monosodium urate crystal in articular structures and culminating in an innate immune response, mediated by the NLRP3 inflammasome, to the deposited crystals. Large genome-wide association studies (GWAS) of serum urate levels initially identified the genetic variants with the strongest effects, mapping mainly to genes that encode urate transporters in the kidney and gut. Other GWAS highlighted the importance of uncommon genetic variants. More recently, genetic and epigenetic genome-wide studies have revealed new pathways in the inflammatory process of gout, including genetic associations with epigenomic modifiers. Epigenome-wide association studies are also implicating epigenomic remodelling in gout, which perhaps regulates the responsiveness of the innate immune system to monosodium urate crystals. Notably, genes implicated in gout GWAS do not include those encoding components of the NLRP3 inflammasome itself, but instead include genes encoding molecules involved in its regulation. Knowledge of the molecular mechanisms underlying gout has advanced through the translation of genetic associations into specific molecular mechanisms. Notable examples include ABCG2, HNF4A, PDZK1, MAF and IL37. Current genetic studies are dominated by participants of European ancestry; however, studies focusing on other population groups are discovering informative population-specific variants associated with gout. Genetic, epigenetic and transcriptomic studies in hyperuricaemia and gout have, in the past 6 years, provided important insights into the underlying molecular mechanisms, revealing new inflammatory pathways and epigenetic factors and expanding research beyond European populations.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"510-523"},"PeriodicalIF":29.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590798","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

Itaconate targets fibroblast-like synoviocytes in RA 伊塔康酸可靶向治疗风湿性关节炎的成纤维细胞样滑膜细胞

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-07-10 DOI: 10.1038/s41584-024-01142-4

Sarah Onuora

引用次数: 0

Update on the pathophysiology and treatment of primary Sjögren syndrome 原发性斯约格伦综合征的最新病理生理学和治疗方法。

IF 29.4 1区医学

Nature Reviews Rheumatology Pub Date : 2024-07-09 DOI: 10.1038/s41584-024-01135-3

Chiara Baldini, Giovanni Fulvio, Gaetano La Rocca, Francesco Ferro

{"title":"Update on the pathophysiology and treatment of primary Sjögren syndrome","authors":"Chiara Baldini, Giovanni Fulvio, Gaetano La Rocca, Francesco Ferro","doi":"10.1038/s41584-024-01135-3","DOIUrl":"10.1038/s41584-024-01135-3","url":null,"abstract":"Sjögren syndrome or Sjögren disease is a chronic form of autoimmune epithelitis characterized by lymphocytic infiltration of the exocrine glands, particularly the salivary and lacrimal glands, leading to progressive glandular dysfunction and subsequent xerostomia and xerophthalmia. Other common manifestations include pain and fatigue, various systemic manifestations and non-Hodgkin’s lymphoma. Sjögren syndrome is therefore a complex and disabling disease associated with a reduced quality of life and with considerable long-term damage. Most of the available treatments are merely symptomatic with limited efficacy in both preventing glandular damage and suppressing systemic disease activity. In the past 10 years, great progress has been made in understanding the pathophysiology of Sjögren syndrome, opening new avenues towards a more targeted and individualized therapeutic approach to the disease. Indeed, several randomized controlled trials have just been completed or are poised to commence evaluating the effectiveness of novel drugs targeting both innate and adaptive immune pathways, including pro-inflammatory cytokines, the type I interferon system, B cell activation, B cell and T cell co-stimulation pathway, and ectopic germinal centre formation. Novel clinical trials are also ongoing exploring various targeted approaches (that is, IgG recycling inhibition, nuclease therapy and CAR-T cell therapy) for Sjögren syndrome. Sjögren syndrome is a chronic autoimmune disease affecting exocrine glands, causing dryness and systemic symptoms. Treatment has been primarily symptomatic, but advances in our understanding of its pathophysiology offer promise for targeted therapies, aiming for personalized care and improved outcomes.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 8","pages":"473-491"},"PeriodicalIF":29.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563769","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