Pub Date : 2024-09-26DOI: 10.1038/s41584-024-01170-0
Denis Poddubnyy
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.
{"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}
Pub Date : 2024-09-25DOI: 10.1038/s41584-024-01172-y
Holly Webster
Findings show a role for the PU.1–IL-9 axis in TH9 cells in the pathogenesis of RA.
研究结果表明，TH9 细胞中的 PU.1-IL-9 轴在 RA 的发病机制中发挥作用。
{"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}
Pub Date : 2024-09-24DOI: 10.1038/s41584-024-01158-w
Julia Lichtnekert, Hans-Joachim Anders
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.
{"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}
Pub Date : 2024-09-20DOI: 10.1038/s41584-024-01171-z
Michael Z Miao,Janice S Lee,Kenneth M Yamada,Richard F Loeser
{"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":"https://doi.org/10.1038/s41584-024-01171-z","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"23 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1038/s41584-024-01153-1
Anniina Virtanen, Francesca Romana Spinelli, Jean Baptiste Telliez, John J. O’Shea, Olli Silvennoinen, Massimo Gadina
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.
细胞因子是免疫系统的通讯工具，在许多生物反应中发挥关键作用，并影响免疫反应。当细胞因子的产生或其生物活性出现异常时，免疫反应的平衡就会被改变，从而导致自身免疫性疾病和炎症性疾病等多种病症的发生。细胞因子与细胞上的特定受体结合，引发被称为 Janus 激酶（JAKs）的细胞内酶的活化。JAK家族由四个成员组成，即JAK1、JAK2、JAK3和酪氨酸激酶2，它们对细胞因子的胞内信号传导至关重要。自 2010 年代中期以来，多种 JAK 抑制剂已被批准用于炎症和血液病适应症。目前，已批准的 JAK 抑制剂已证明具有临床疗效；然而，提高对特定 JAK 的选择性可能会增强安全性，目前已采用不同的策略来提高 JAK 的选择性。在本报告中，我们将讨论 JAK 抑制剂的背景、目前批准的适应症和不良反应，以及该领域的新进展。我们讨论了 JAK 选择性及其与疗效的相关性，并介绍了 JAK 靶向的新模式以及 JAK 抑制剂作用的新方面。
{"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}
Pub Date : 2024-09-09DOI: 10.1038/s41584-024-01164-y
Mehrdad Pazhouhandeh, Di Yu
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.
I型干扰素在系统性红斑狼疮（SLE）的免疫发病机制中起着至关重要的作用。对来自系统性红斑狼疮患者的 CD4+ T 细胞的分析表明，I 型干扰素与转录调节因子 AHR 和 JUN 相互干预，下调促进组织再生的 IL-22 的表达，上调支持淋巴结构形成的 CXCL13 的表达。
{"title":"Interferon disrupts immune and tissue homeostasis in SLE via CXCL13","authors":"Mehrdad Pazhouhandeh, Di Yu","doi":"10.1038/s41584-024-01164-y","DOIUrl":"https://doi.org/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":"34 1","pages":""},"PeriodicalIF":33.7,"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}
Pub Date : 2024-09-09DOI: 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
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.
类风湿性关节炎（RA）是一种具有潜在破坏性的自身免疫性疾病。绝大多数 RA 患者的抗瓜氨酸蛋白抗体（ACPA）、类风湿因子或其他自身抗体血清反应呈阳性。符合分类标准（临床 RA）的临床明显炎症性关节炎发病前，ACPA 血清阳性反应平均持续 3-5 年，这段时间对于未显示关节炎症状的 ACPA 阳性个体而言，被称为 RA "高危 "期；对于已知已发展为临床 RA 的个体而言，则称为 "RA 前 "期。先前对有 RA 风险的个体进行的研究将肺粘膜炎症与 ACPA 和类风湿因子的局部产生联系起来，从而提出了 "粘膜起源假说"。最近的研究表明，存在多种不同的粘膜部位特异性机制，驱动着RA的演变。有迹象表明，RA 高危人群和 RA 患者的粪便中含有一种细菌菌株，这种菌株在动物模型中具有致关节炎活性，在患者体内有利于 T 辅助细胞 17（TH17）的反应。牙周炎症和口腔微生物群也被认为通过破坏粘膜屏障促进关节炎的发展。在此，我们认为粘膜部位及其相关的微生物菌株可通过不同的致病机制促进关节炎的演变，这些机制可被视为致病粘膜内型。作为精准医疗方法的一部分，未来用于风险期预防的疗法，或作为活动性关节炎的临床RA治疗方法，可能必须解决这些不同机制的问题。
{"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}
Pub Date : 2024-09-06DOI: 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
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.
{"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}
Pub Date : 2024-09-05DOI: 10.1038/s41584-024-01166-w
Jessica McHugh
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.
{"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}
Pub Date : 2024-09-04DOI: 10.1038/s41584-024-01152-2
Yogita Ghodke-Puranik, Mikhail Olferiev, Mary K. Crow
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.
{"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}
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