Pub Date : 2024-09-02DOI: 10.1038/s41584-024-01162-0
Satoshi Kubo, Yoshiya Tanaka
Immune health has been considered impossible to assess through the use of traditional biomarkers. The newly devised immune health metric (IHM) integrates diverse biological data to quantify immune function, offering a comprehensive indicator for the evaluation of immune health. The potential of the IHM to distinguish healthy individuals from patients with monogenic or polygenic immune-mediated diseases might lead to revolutionary changes in treatment strategies for rheumatic diseases.
{"title":"The immune health metric as an indicator of health and disease","authors":"Satoshi Kubo, Yoshiya Tanaka","doi":"10.1038/s41584-024-01162-0","DOIUrl":"10.1038/s41584-024-01162-0","url":null,"abstract":"Immune health has been considered impossible to assess through the use of traditional biomarkers. The newly devised immune health metric (IHM) integrates diverse biological data to quantify immune function, offering a comprehensive indicator for the evaluation of immune health. The potential of the IHM to distinguish healthy individuals from patients with monogenic or polygenic immune-mediated diseases might lead to revolutionary changes in treatment strategies for rheumatic diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 12","pages":"743-744"},"PeriodicalIF":29.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130730","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}
Pub Date : 2024-09-02DOI: 10.1038/s41584-024-01149-x
Maya H. Buch, Ziad Mallat, Marc R. Dweck, Jason M. Tarkin, Declan P. O’Regan, Vanessa Ferreira, Taryn Youngstein, Sven Plein
Immune-mediated inflammatory diseases (IMIDs) are a spectrum of disorders of overlapping immunopathogenesis, with a prevalence of up to 10% in Western populations and increasing incidence in developing countries. Although targeted treatments have revolutionized the management of rheumatic IMIDs, cardiovascular involvement confers an increased risk of mortality and remains clinically under-recognized. Cardiovascular pathology is diverse across rheumatic IMIDs, ranging from premature atherosclerotic cardiovascular disease (ASCVD) to inflammatory cardiomyopathy, which comprises myocardial microvascular dysfunction, vasculitis, myocarditis and pericarditis, and heart failure. Epidemiological and clinical data imply that rheumatic IMIDs and associated cardiovascular disease share common inflammatory mechanisms. This concept is strengthened by emergent trials that indicate improved cardiovascular outcomes with immune modulators in the general population with ASCVD. However, not all disease-modifying therapies that reduce inflammation in IMIDs such as rheumatoid arthritis demonstrate equally beneficial cardiovascular effects, and the evidence base for treatment of inflammatory cardiomyopathy in patients with rheumatic IMIDs is lacking. Specific diagnostic protocols for the early detection and monitoring of cardiovascular involvement in patients with IMIDs are emerging but are in need of ongoing development. This Review summarizes current concepts on the potentially targetable inflammatory mechanisms of cardiovascular pathology in rheumatic IMIDs and discusses how these concepts can be considered for the diagnosis and management of cardiovascular involvement across rheumatic IMIDs, with an emphasis on the potential of cardiovascular imaging for risk stratification, early detection and prognostication. Cardiovascular involvement is one of the many manifestations of rheumatic immune-mediated inflammatory diseases (IMIDs) that increase mortality. The pathogenesis of atherosclerosis and inflammatory cardiomyopathies involves inflammatory pathways common with those operating and targeted in rheumatic IMIDs. Here, Maya Buch and colleagues discuss implications of these shared pathways for the prevention, detection and management of cardiovascular involvement in patients with rheumatic IMIDs, while highlighting complexities and open questions.
{"title":"Current understanding and management of cardiovascular involvement in rheumatic immune-mediated inflammatory diseases","authors":"Maya H. Buch, Ziad Mallat, Marc R. Dweck, Jason M. Tarkin, Declan P. O’Regan, Vanessa Ferreira, Taryn Youngstein, Sven Plein","doi":"10.1038/s41584-024-01149-x","DOIUrl":"10.1038/s41584-024-01149-x","url":null,"abstract":"Immune-mediated inflammatory diseases (IMIDs) are a spectrum of disorders of overlapping immunopathogenesis, with a prevalence of up to 10% in Western populations and increasing incidence in developing countries. Although targeted treatments have revolutionized the management of rheumatic IMIDs, cardiovascular involvement confers an increased risk of mortality and remains clinically under-recognized. Cardiovascular pathology is diverse across rheumatic IMIDs, ranging from premature atherosclerotic cardiovascular disease (ASCVD) to inflammatory cardiomyopathy, which comprises myocardial microvascular dysfunction, vasculitis, myocarditis and pericarditis, and heart failure. Epidemiological and clinical data imply that rheumatic IMIDs and associated cardiovascular disease share common inflammatory mechanisms. This concept is strengthened by emergent trials that indicate improved cardiovascular outcomes with immune modulators in the general population with ASCVD. However, not all disease-modifying therapies that reduce inflammation in IMIDs such as rheumatoid arthritis demonstrate equally beneficial cardiovascular effects, and the evidence base for treatment of inflammatory cardiomyopathy in patients with rheumatic IMIDs is lacking. Specific diagnostic protocols for the early detection and monitoring of cardiovascular involvement in patients with IMIDs are emerging but are in need of ongoing development. This Review summarizes current concepts on the potentially targetable inflammatory mechanisms of cardiovascular pathology in rheumatic IMIDs and discusses how these concepts can be considered for the diagnosis and management of cardiovascular involvement across rheumatic IMIDs, with an emphasis on the potential of cardiovascular imaging for risk stratification, early detection and prognostication. Cardiovascular involvement is one of the many manifestations of rheumatic immune-mediated inflammatory diseases (IMIDs) that increase mortality. The pathogenesis of atherosclerosis and inflammatory cardiomyopathies involves inflammatory pathways common with those operating and targeted in rheumatic IMIDs. Here, Maya Buch and colleagues discuss implications of these shared pathways for the prevention, detection and management of cardiovascular involvement in patients with rheumatic IMIDs, while highlighting complexities and open questions.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"614-634"},"PeriodicalIF":29.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130734","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}
Pub Date : 2024-08-23DOI: 10.1038/s41584-024-01161-1
Holly Webster
In a new study, researchers use M2 macrophage exosomes and membranes to disguise a tri-drug-carrying nanosystem that reduces inflammation and urate levels in rats with gouty arthritis.
{"title":"Macrophage-coated nanocarriers for gouty arthritis","authors":"Holly Webster","doi":"10.1038/s41584-024-01161-1","DOIUrl":"10.1038/s41584-024-01161-1","url":null,"abstract":"In a new study, researchers use M2 macrophage exosomes and membranes to disguise a tri-drug-carrying nanosystem that reduces inflammation and urate levels in rats with gouty arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"597-597"},"PeriodicalIF":29.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042461","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}
Pub Date : 2024-08-22DOI: 10.1038/s41584-024-01156-y
Roberto Díaz-Peña, Olufemi Adelowo
Increasing diversity in genomic studies is essential to advance precision medicine and health equity in rheumatic diseases. Addressing structural and logistical barriers to include underrepresented populations, particularly in Africa and Latin America, could improve our understanding of rheumatic diseases and lead to better healthcare outcomes for all.
{"title":"Advancing equity in genomic medicine for rheumatology","authors":"Roberto Díaz-Peña, Olufemi Adelowo","doi":"10.1038/s41584-024-01156-y","DOIUrl":"10.1038/s41584-024-01156-y","url":null,"abstract":"Increasing diversity in genomic studies is essential to advance precision medicine and health equity in rheumatic diseases. Addressing structural and logistical barriers to include underrepresented populations, particularly in Africa and Latin America, could improve our understanding of rheumatic diseases and lead to better healthcare outcomes for all.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"595-596"},"PeriodicalIF":29.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036419","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}
Pub Date : 2024-08-20DOI: 10.1038/s41584-024-01157-x
Maria Papatriantafyllou
The PDZ domain-containing scaffold protein PDZK1 is downregulated in osteoarthritic chondrocytes and is linked to mitochondrial dysfunction and chondrocyte senescence.
{"title":"PDZK1 downregulation linked to mitochondrial dysfunction in OA","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-024-01157-x","DOIUrl":"10.1038/s41584-024-01157-x","url":null,"abstract":"The PDZ domain-containing scaffold protein PDZK1 is downregulated in osteoarthritic chondrocytes and is linked to mitochondrial dysfunction and chondrocyte senescence.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 10","pages":"597-597"},"PeriodicalIF":29.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009049","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}
Pub Date : 2024-08-09DOI: 10.1038/s41584-024-01146-0
Renpeng Zhou, Wenyu Fu, Dmytro Vasylyev, Stephen G. Waxman, Chuan-ju Liu
Osteoarthritis (OA) is a highly prevalent joint disease that causes substantial disability, yet effective approaches to disease prevention or to the delay of OA progression are lacking. Emerging evidence has pinpointed ion channels as pivotal mediators in OA pathogenesis and as promising targets for disease-modifying treatments. Preclinical studies have assessed the potential of a variety of ion channel modulators to modify disease pathways involved in cartilage degeneration, synovial inflammation, bone hyperplasia and pain, and to provide symptomatic relief in models of OA. Some of these modulators are currently being evaluated in clinical trials. This review explores the structures and functions of ion channels, including transient receptor potential channels, Piezo channels, voltage-gated sodium channels, voltage-dependent calcium channels, potassium channels, acid-sensing ion channels, chloride channels and the ATP-dependent P2XR channels in the osteoarthritic joint. The discussion spans channel-targeting drug discovery and potential clinical applications, emphasizing opportunities for further research, and underscoring the growing clinical impact of ion channel biology in OA. Ion channels have key functions in chondrocytes, bone cells, immune cells and neurons. Liu and colleagues discuss how these functions might contribute to cartilage degeneration, bone formation inflammation and pain in osteoarthritis, and highlight the therapeutic potential of ion channel modulators.
骨关节炎（OA）是一种高发的关节疾病，会导致严重的残疾，但目前还缺乏有效的方法来预防疾病或延缓 OA 的发展。新的证据表明，离子通道是导致 OA 发病的关键介质，也是有希望改变病情的治疗目标。临床前研究评估了多种离子通道调节剂的潜力，以改变涉及软骨退化、滑膜炎症、骨质增生和疼痛的疾病通路，并在 OA 模型中缓解症状。其中一些调节剂目前正在临床试验中进行评估。本综述探讨了骨关节炎关节中离子通道的结构和功能，包括瞬时受体电位通道、压电通道、电压门控钠通道、电压依赖性钙通道、钾通道、酸感应离子通道、氯离子通道和 ATP 依赖性 P2XR 通道。讨论涉及通道靶向药物的发现和潜在的临床应用，强调了进一步研究的机会，并强调了离子通道生物学在 OA 中日益增长的临床影响。
{"title":"Ion channels in osteoarthritis: emerging roles and potential targets","authors":"Renpeng Zhou, Wenyu Fu, Dmytro Vasylyev, Stephen G. Waxman, Chuan-ju Liu","doi":"10.1038/s41584-024-01146-0","DOIUrl":"10.1038/s41584-024-01146-0","url":null,"abstract":"Osteoarthritis (OA) is a highly prevalent joint disease that causes substantial disability, yet effective approaches to disease prevention or to the delay of OA progression are lacking. Emerging evidence has pinpointed ion channels as pivotal mediators in OA pathogenesis and as promising targets for disease-modifying treatments. Preclinical studies have assessed the potential of a variety of ion channel modulators to modify disease pathways involved in cartilage degeneration, synovial inflammation, bone hyperplasia and pain, and to provide symptomatic relief in models of OA. Some of these modulators are currently being evaluated in clinical trials. This review explores the structures and functions of ion channels, including transient receptor potential channels, Piezo channels, voltage-gated sodium channels, voltage-dependent calcium channels, potassium channels, acid-sensing ion channels, chloride channels and the ATP-dependent P2XR channels in the osteoarthritic joint. The discussion spans channel-targeting drug discovery and potential clinical applications, emphasizing opportunities for further research, and underscoring the growing clinical impact of ion channel biology in OA. Ion channels have key functions in chondrocytes, bone cells, immune cells and neurons. Liu and colleagues discuss how these functions might contribute to cartilage degeneration, bone formation inflammation and pain in osteoarthritis, and highlight the therapeutic potential of ion channel modulators.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 9","pages":"545-564"},"PeriodicalIF":29.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909158","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}
Pub Date : 2024-08-07DOI: 10.1038/s41584-024-01145-1
Seza Ozen, Ivona Aksentijevich
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.
{"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}
Pub Date : 2024-08-07DOI: 10.1038/s41584-024-01143-3
Marie Binvignat, Jérémie Sellam, Francis Berenbaum, David T. Felson
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.
肥胖在骨关节炎（OA）相关疼痛中起着关键和多方面的作用，其影响超出了体重指数（BMI）的机理。肥胖通过与 OA 相关疼痛有关的各种可改变的风险因素直接或间接地产生影响。脂肪组织功能障碍通过局部和全身炎症、免疫功能障碍以及促炎症细胞因子和脂肪因子的产生，与 OA 相关疼痛密切相关。脂肪组织功能障碍与代谢综合征有着错综复杂的联系，代谢综合征对 OA 相关疼痛具有独立的特定影响，有别于与体重指数的关联。肥胖、脂肪组织功能障碍和代谢综合征之间的相互作用通过不同的疼痛机制（包括痛觉疼痛、外周敏感化和中枢敏感化）影响 OA 相关疼痛。这些复杂的相互作用导致 OA 和肥胖症患者的疼痛体验加剧。此外，肥胖症患者的疼痛管理策略效率较低。重要的是，针对肥胖和代谢综合征的治疗干预有望控制 OA 相关疼痛。深入了解肥胖、代谢综合征和 OA 相关疼痛之间错综复杂的关系至关重要，这对改善疼痛管理和开发 OA 创新治疗方案具有重要意义。
{"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}
Pub Date : 2024-08-06DOI: 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
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.
嵌合抗原受体（CAR）T 细胞在靶向清除 B 细胞系细胞方面非常有效。CAR T 细胞疗法已成为复发或难治性 B 细胞恶性肿瘤患者的标准治疗方法。此外，转基因 T 细胞具有消耗 B 细胞和/或浆细胞的能力，对自身免疫性疾病具有巨大的治疗潜力。在过去几年中，基于 CD19 和 B 细胞成熟抗原（BCMA）的 CAR T 细胞疗法已被应用于各种 B 细胞介导的自身免疫性疾病，包括系统性红斑狼疮、特发性炎症性肌病、系统性硬化症、神经性脊髓炎视网膜频谱障碍、重症肌无力和多发性硬化症。这种方法背后的科学原理是，深度消耗 B 细胞（包括自反应性 B 细胞克隆）可以恢复正常的免疫功能，即所谓的免疫重置。在本综述中，我们将讨论 CAR T 细胞疗法治疗自身免疫性疾病的重要方面，包括与患者选择、安全性、疗效和医疗管理有关的注意事项。这些考虑因素基于 CAR T 细胞疗法治疗自身免疫性疾病的早期经验，随着 CAR T 细胞疗法治疗自身免疫性疾病领域的持续快速发展，这些问题仍将不断完善和调整。
{"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}
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