Patients with systemic lupus erythematosus (SLE) experience greater cardiovascular morbidity and mortality compared to the general population. It is known that endothelial dysfunction, an early indicator of atherosclerosis development, can arise even without the presence of conventional cardiovascular risk factors. In fact, the risk factors contributing to cardiovascular disease can be classified into traditional risk factors and those uniquely associated with SLE such as disease activity, autoantibodies, etc.Furthermore, the pathogenesis of cardiovascular disease in SLE is linked to the activation of both the innate and adaptive immune systems. Given these findings, it is essential for clinicians to acknowledge the heightened CVD risk in SLE patients, perform comprehensive screenings for cardiovascular risk factors, and implement aggressive treatment strategies for those who exhibit signs of clinical CVD. The aim of this review is to summarize the findings on cardiovascular disease in SLE and to examine potential screening and therapeutic strategies for clinical practice.
{"title":"Cardiovascular disease risk in systemic lupus erythematous: Certainties and controversies","authors":"Fabiola Atzeni , Ignasi Rodríguez-Pintó , Ricard Cervera","doi":"10.1016/j.autrev.2024.103646","DOIUrl":"10.1016/j.autrev.2024.103646","url":null,"abstract":"<div><div>Patients with systemic lupus erythematosus (SLE) experience greater cardiovascular morbidity and mortality compared to the general population. It is known that endothelial dysfunction, an early indicator of atherosclerosis development, can arise even without the presence of conventional cardiovascular risk factors. In fact, the risk factors contributing to cardiovascular disease can be classified into traditional risk factors and those uniquely associated with SLE such as disease activity, autoantibodies, etc.Furthermore, the pathogenesis of cardiovascular disease in SLE is linked to the activation of both the innate and adaptive immune systems. Given these findings, it is essential for clinicians to acknowledge the heightened CVD risk in SLE patients, perform comprehensive screenings for cardiovascular risk factors, and implement aggressive treatment strategies for those who exhibit signs of clinical CVD. The aim of this review is to summarize the findings on cardiovascular disease in SLE and to examine potential screening and therapeutic strategies for clinical practice.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 10","pages":"Article 103646"},"PeriodicalIF":9.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328035","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 : 2024-09-21DOI: 10.1016/j.autrev.2024.103642
Dennis McGonagle , Sami Giryes
The immunological basis for cardiac deaths remote from potential triggering viral infection, including SARS-CoV-2 infection, remains enigmatic. Cardiac surface inflammation, including the pericardium, epicardium and superficial myocardium with associated coronary artery vasculitis in infant Kawasaki Disease (KD) and multisystem inflammatory syndrome in children (MIS-C) is well recognised. In this perspective, we review the evidence pointing towards prominent post-viral infection related epicardial inflammation in older subjects, resulting in atherosclerotic plaque destabilisation with seemingly unrelated myocardial infarction that may be temporally distant from the actual infectious triggers. Cardiac surface inflammation in the relatively immune cell rich tissues in the territory though where the coronary arteries traverse is common in the adult post-COVD pneumonic phase and is also well described after vaccination including pre-COVID era vaccinations. Immunologically, the pericardium/epicardium tissue was known to be critical for coronary artery territory atherosclerotic disease prior to the COVID-19 era and may be linked to the involvement of the coronary artery vasa vasorum that physiologically oxygenates the coronary artery walls. We highlight how viral infection or vaccination-associated diffuse epicardial tissue inflammation adjacent to the coronary artery vasa vasorum territory represents a critical unifying concept for seemingly unrelated fatal coronary artery atherosclerotic disease, that could occur soon after or remote from infection or vaccination in adults. Mechanistically, such epicardial inflammation impacting coronary artery vasa vasorum immunity acts as gateways towards the slow destabilisation of pre-existing atherosclerotic plaques, with resultant myocardial infarction and other cardiac pathology. This model offers immunologists and academic cardiologists an immunopathological roadmap between innocuous viral infections or vaccinations and seemingly temporally remote “unrelated” atherosclerotic disease with excess cardiac deaths.
{"title":"An immunology model for accelerated coronary atherosclerosis and unexplained sudden death in the COVID-19 era","authors":"Dennis McGonagle , Sami Giryes","doi":"10.1016/j.autrev.2024.103642","DOIUrl":"10.1016/j.autrev.2024.103642","url":null,"abstract":"<div><div>The immunological basis for cardiac deaths remote from potential triggering viral infection, including SARS-CoV-2 infection, remains enigmatic. Cardiac surface inflammation, including the pericardium, epicardium and superficial myocardium with associated coronary artery vasculitis in infant Kawasaki Disease (KD) and multisystem inflammatory syndrome in children (MIS-C) is well recognised. In this perspective, we review the evidence pointing towards prominent post-viral infection related epicardial inflammation in older subjects, resulting in atherosclerotic plaque destabilisation with seemingly unrelated myocardial infarction that may be temporally distant from the actual infectious triggers. Cardiac surface inflammation in the relatively immune cell rich tissues in the territory though where the coronary arteries traverse is common in the adult post-COVD pneumonic phase and is also well described after vaccination including pre-COVID era vaccinations. Immunologically, the pericardium/epicardium tissue was known to be critical for coronary artery territory atherosclerotic disease prior to the COVID-19 era and may be linked to the involvement of the coronary artery vasa vasorum that physiologically oxygenates the coronary artery walls. We highlight how viral infection or vaccination-associated diffuse epicardial tissue inflammation adjacent to the coronary artery vasa vasorum territory represents a critical unifying concept for seemingly unrelated fatal coronary artery atherosclerotic disease, that could occur soon after or remote from infection or vaccination in adults. Mechanistically, such epicardial inflammation impacting coronary artery vasa vasorum immunity acts as gateways towards the slow destabilisation of pre-existing atherosclerotic plaques, with resultant myocardial infarction and other cardiac pathology. This model offers immunologists and academic cardiologists an immunopathological roadmap between innocuous viral infections or vaccinations and seemingly temporally remote “unrelated” atherosclerotic disease with excess cardiac deaths.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 11","pages":"Article 103642"},"PeriodicalIF":9.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.autrev.2024.103645
Kaylyn Rowsey , Seth Sims , Merhawit Ghebrehiwet , Andrew Wilson , Josh Autaubo , Payton Clark , Simran Demla , Alicia Ito Ford , Matt Vassar
Background
Systemic lupus erythematosus (SLE) exhibits a mortality rate four times higher in historically marginalized populations compared to the general population. It is essential for clinical trials to accurately represent the disease population to effectively evaluate treatment modalities. However, the current trial design lacks appropriate diversity, limiting the generalizability of results. We aim to assess the recruitment and retention strategies of historically marginalized populations in SLE clinical trials.
Methods
In this cross-sectional analysis, relevant clinical trials were obtained in a comprehensive search of MEDLINE (PubMed) and Embase (Elsevier) in May of 2024. Included trials were published between January 1, 2018, and December 31, 2023, with a focus on SLE interventions. Reviewers KR and SS independently performed screening and data extraction via a standardized Google Form. The main outcome measured was the usage of recruitment and retention strategies, concerning under-resourced populations. All statistical analyses were performed via Stata 18 SE.
Findings
Our initial database search returned 747 trials, but only 86 were included in this sample. Of these, 4/86 (4.7 %) implemented recruitment strategies while 6/86 (7.0 %) reported the use of specific retention strategies. Nineteen of the 86 studies (22.1 %) reported challenges to the recruitment of inequitable populations, primarily identifying the disproportionate representation of female participants and socioeconomic obstacles as a limitation.
Interpretation
Key strengths include a thorough methodology from adherence to PRISMA guidelines and generalizable findings with the inclusion of international trials. Limitations include publication bias and exclusion of trials in non-English languages. Our study highlights the need for practical initiation of effective recruitment and retention strategies that aim to engage historically marginalized populations in SLE clinical trials. Addressing these gaps is necessary to prioritize the participation of inequitable populations, increase standardization of SLE treatments, and improve the relevance of SLE research.
背景系统性红斑狼疮（SLE）在历史边缘人群中的死亡率是普通人群的四倍。临床试验必须准确代表患病人群，才能有效评估治疗方法。然而，目前的试验设计缺乏适当的多样性，限制了试验结果的推广性。我们旨在评估系统性红斑狼疮临床试验中历来被边缘化的人群的招募和保留策略。在这项横断面分析中，我们于 2024 年 5 月对 MEDLINE（PubMed）和 Embase（Elsevier）进行了全面检索，获得了相关的临床试验。纳入的试验发表于 2018 年 1 月 1 日至 2023 年 12 月 31 日之间，重点关注系统性红斑狼疮干预措施。审稿人 KR 和 SS 通过标准化的谷歌表格独立进行筛选和数据提取。衡量的主要结果是招募和保留策略的使用情况，涉及资源不足的人群。所有统计分析均通过 Stata 18 SE 进行。其中，4/86（4.7%）实施了招募策略，6/86（7.0%）报告使用了特定的保留策略。86项研究中有19项（22.1%）报告了在招募不公平人群时遇到的挑战，主要指出女性参与者比例过高和社会经济障碍是限制因素之一。局限性包括发表偏差和排除了非英语语言的试验。我们的研究强调了切实启动有效招募和保留策略的必要性，这些策略旨在让历史上被边缘化的人群参与系统性红斑狼疮临床试验。要优先考虑不公平人群的参与、提高系统性红斑狼疮治疗的标准化程度以及改善系统性红斑狼疮研究的相关性，就必须解决这些差距。
{"title":"Assessing recruitment and retention strategies in clinical trials for inequitable populations in systemic lupus erythematosus: A cross-sectional analysis","authors":"Kaylyn Rowsey , Seth Sims , Merhawit Ghebrehiwet , Andrew Wilson , Josh Autaubo , Payton Clark , Simran Demla , Alicia Ito Ford , Matt Vassar","doi":"10.1016/j.autrev.2024.103645","DOIUrl":"10.1016/j.autrev.2024.103645","url":null,"abstract":"<div><h3>Background</h3><p>Systemic lupus erythematosus (SLE) exhibits a mortality rate four times higher in historically marginalized populations compared to the general population. It is essential for clinical trials to accurately represent the disease population to effectively evaluate treatment modalities. However, the current trial design lacks appropriate diversity, limiting the generalizability of results. We aim to assess the recruitment and retention strategies of historically marginalized populations in SLE clinical trials.</p></div><div><h3>Methods</h3><p>In this cross-sectional analysis, relevant clinical trials were obtained in a comprehensive search of MEDLINE (PubMed) and Embase (Elsevier) in May of 2024. Included trials were published between January 1, 2018, and December 31, 2023, with a focus on SLE interventions. Reviewers KR and SS independently performed screening and data extraction via a standardized Google Form. The main outcome measured was the usage of recruitment and retention strategies, concerning under-resourced populations. All statistical analyses were performed via Stata 18 SE.</p></div><div><h3>Findings</h3><p>Our initial database search returned 747 trials, but only 86 were included in this sample. Of these, 4/86 (4.7 %) implemented recruitment strategies while 6/86 (7.0 %) reported the use of specific retention strategies. Nineteen of the 86 studies (22.1 %) reported challenges to the recruitment of inequitable populations, primarily identifying the disproportionate representation of female participants and socioeconomic obstacles as a limitation.</p></div><div><h3>Interpretation</h3><p>Key strengths include a thorough methodology from adherence to PRISMA guidelines and generalizable findings with the inclusion of international trials. Limitations include publication bias and exclusion of trials in non-English languages. Our study highlights the need for practical initiation of effective recruitment and retention strategies that aim to engage historically marginalized populations in SLE clinical trials. Addressing these gaps is necessary to prioritize the participation of inequitable populations, increase standardization of SLE treatments, and improve the relevance of SLE research.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 11","pages":"Article 103645"},"PeriodicalIF":9.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274689","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}
Over 100 diseases have been recognized as autoimmune in nature, collectively affecting ∼20 % of the population in industrialized countries. These conditions are more prevalent among women of childbearing age, reflecting the potential association between alterations in the immune-neuroendocrine network, on the one hand, and autoimmune conditions, on the other. Prolactin (PRL), a polypeptide hormone that is primarily (but not only) secreted by the lactotrophic cells of the pituitary gland, is a critical element of the immune-neuroendocrine network. Although this hormone has several nonimmune functions, its role in regulating immune responses and affecting autoimmune inflammation is particularly enigmatic and controversial. Indeed, PRL interacts with various immune cells to bolster the body defenses, but also potentially to exacerbate autoimmune conditions. Understanding how and when PRL acts as a ‘friend or foe’ is crucial for unraveling its role as a potential therapeutic target in the management of autoimmune diseases (AIDs). This review therefore provides a critical overview of PRL's role in the immune system, and of the influence of this pleiotropic hormone in the development of autoimmunity.
有 100 多种疾病被认为是自身免疫性疾病，在工业化国家中，约有 20% 的人患有这些疾病。这些疾病在育龄妇女中更为普遍，反映了免疫-神经内分泌网络的改变与自身免疫疾病之间的潜在联系。催乳素（PRL）是一种多肽激素，主要（但不只是）由垂体的泌乳细胞分泌，是免疫-神经内分泌网络的一个关键要素。虽然这种激素具有多种非免疫功能，但它在调节免疫反应和影响自身免疫性炎症方面的作用却尤为神秘和具有争议性。事实上，PRL 可与各种免疫细胞相互作用，增强机体防御能力，但也有可能加剧自身免疫性疾病。了解 PRL 如何以及何时充当 "敌友"，对于揭示其作为潜在治疗靶点在自身免疫性疾病（AIDs）治疗中的作用至关重要。因此，本综述对 PRL 在免疫系统中的作用以及这种多效应激素在自身免疫发展过程中的影响进行了重要概述。
{"title":"Prolactin's paradox: Friend, foe, or both in immune regulation?","authors":"Vânia Borba , Pedro Carrera-Bastos , Gisele Zandman-Goddard , Alejandro Lucia , Yehuda Shoenfeld","doi":"10.1016/j.autrev.2024.103643","DOIUrl":"10.1016/j.autrev.2024.103643","url":null,"abstract":"<div><div>Over 100 diseases have been recognized as autoimmune in nature, collectively affecting ∼20 % of the population in industrialized countries. These conditions are more prevalent among women of childbearing age, reflecting the potential association between alterations in the immune-neuroendocrine network, on the one hand, and autoimmune conditions, on the other. Prolactin (PRL), a polypeptide hormone that is primarily (but not only) secreted by the lactotrophic cells of the pituitary gland, is a critical element of the immune-neuroendocrine network. Although this hormone has several nonimmune functions, its role in regulating immune responses and affecting autoimmune inflammation is particularly enigmatic and controversial. Indeed, PRL interacts with various immune cells to bolster the body defenses, but also potentially to exacerbate autoimmune conditions. Understanding how and when PRL acts as a ‘friend or foe’ is crucial for unraveling its role as a potential therapeutic target in the management of autoimmune diseases (AIDs). This review therefore provides a critical overview of PRL's role in the immune system, and of the influence of this pleiotropic hormone in the development of autoimmunity.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 11","pages":"Article 103643"},"PeriodicalIF":9.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279914","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 : 2024-09-19DOI: 10.1016/j.autrev.2024.103644
Stefen Brady , Joanna Poulton , Sylviane Muller
Inclusion body myositis (IBM) is a late onset sporadic myopathy with a characteristic clinical presentation, but as yet unknown aetiology or effective treatment. Typical clinical features are early predominant asymmetric weakness of finger flexor and knee extensor muscles. Muscle biopsy shows endomysial inflammatory infiltrate, mitochondrial changes, and protein aggregation. Proteostasis (protein turnover) appears to be impaired, linked to potentially dysregulated chaperone-mediated autophagy and mitophagy (a type of mitochondrial quality control). In this review, we bring together the most recent clinical and biological data describing IBM. We then address the question of diagnosing this pathology and the relevance of the current biological markers that characterize IBM. In these descriptions, we put a particular emphasis on data related to the deregulation of autophagic processes and to the mitochondrial-lysosomal crosstalk. Finally, after a short description of current treatments, an overview is provided pointing towards novel therapeutic targets and emerging regulatory molecules that are being explored for treating IBM. Special attention is paid to autophagy inhibitors that may offer innovative breakthrough therapies for patients with IBM.
包涵体肌炎（IBM）是一种晚发型散发性肌病，具有特征性的临床表现，但病因和有效治疗方法尚不清楚。典型的临床特征是早期主要表现为手指屈肌和膝关节伸肌的不对称无力。肌肉活检显示内膜炎症浸润、线粒体变化和蛋白质聚集。蛋白稳态（蛋白质周转）似乎受到损害，这可能与伴侣介导的自噬和线粒体吞噬（线粒体质量控制）失调有关。在这篇综述中，我们汇集了描述 IBM 的最新临床和生物学数据。然后，我们探讨了诊断这种病症的问题，以及当前描述 IBM 特征的生物标记物的相关性。在这些描述中，我们特别强调了与自噬过程失调和线粒体-溶酶体串联相关的数据。最后，在简短介绍了目前的治疗方法后，我们将概述用于治疗 IBM 的新型治疗靶点和即将测试的调节分子。其中特别关注了自噬抑制剂，它们可能为 IBM 患者提供创新性的突破疗法。
{"title":"Inclusion body myositis: Correcting impaired mitochondrial and lysosomal autophagy as a potential therapeutic strategy","authors":"Stefen Brady , Joanna Poulton , Sylviane Muller","doi":"10.1016/j.autrev.2024.103644","DOIUrl":"10.1016/j.autrev.2024.103644","url":null,"abstract":"<div><div>Inclusion body myositis (IBM) is a late onset sporadic myopathy with a characteristic clinical presentation, but as yet unknown aetiology or effective treatment. Typical clinical features are early predominant asymmetric weakness of finger flexor and knee extensor muscles. Muscle biopsy shows endomysial inflammatory infiltrate, mitochondrial changes, and protein aggregation. Proteostasis (protein turnover) appears to be impaired, linked to potentially dysregulated chaperone-mediated autophagy and mitophagy (a type of mitochondrial quality control). In this review, we bring together the most recent clinical and biological data describing IBM. We then address the question of diagnosing this pathology and the relevance of the current biological markers that characterize IBM. In these descriptions, we put a particular emphasis on data related to the deregulation of autophagic processes and to the mitochondrial-lysosomal crosstalk. Finally, after a short description of current treatments, an overview is provided pointing towards novel therapeutic targets and emerging regulatory molecules that are being explored for treating IBM. Special attention is paid to autophagy inhibitors that may offer innovative breakthrough therapies for patients with IBM.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 11","pages":"Article 103644"},"PeriodicalIF":9.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279912","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 : 2024-09-13DOI: 10.1016/j.autrev.2024.103640
Yingzi Zheng , Fangfang Yan , Shasha He , Lianxiang Luo
Ferroptosis is a form of regulated cell death that relies on iron and exhibits unique characteristics, including disrupted iron balance, reduced antioxidant defenses, and abnormal lipid peroxidation. Recent research suggests that ferroptosis is associated with the onset and progression of autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). However, the precise effects and molecular mechanisms remain incompletely understood. This article presents an overview of how ferroptosis mechanisms contribute to the development and advancement of autoimmune diseases, as well as the involvement of various immune cells in linking ferroptosis to autoimmune conditions. It also explores potential drug targets within the ferroptosis pathway and recent advancements in therapeutic approaches aimed at preventing and treating autoimmune diseases by targeting ferroptosis. Lastly, the article discusses the challenges and opportunities in utilizing ferroptosis as a potential therapeutic avenue for autoimmune disorders.
{"title":"Targeting ferroptosis in autoimmune diseases: Mechanisms and therapeutic prospects","authors":"Yingzi Zheng , Fangfang Yan , Shasha He , Lianxiang Luo","doi":"10.1016/j.autrev.2024.103640","DOIUrl":"10.1016/j.autrev.2024.103640","url":null,"abstract":"<div><p>Ferroptosis is a form of regulated cell death that relies on iron and exhibits unique characteristics, including disrupted iron balance, reduced antioxidant defenses, and abnormal lipid peroxidation. Recent research suggests that ferroptosis is associated with the onset and progression of autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). However, the precise effects and molecular mechanisms remain incompletely understood. This article presents an overview of how ferroptosis mechanisms contribute to the development and advancement of autoimmune diseases, as well as the involvement of various immune cells in linking ferroptosis to autoimmune conditions. It also explores potential drug targets within the ferroptosis pathway and recent advancements in therapeutic approaches aimed at preventing and treating autoimmune diseases by targeting ferroptosis. Lastly, the article discusses the challenges and opportunities in utilizing ferroptosis as a potential therapeutic avenue for autoimmune disorders.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 11","pages":"Article 103640"},"PeriodicalIF":9.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274688","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}
Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.
{"title":"Treatment strategies for Spondyloarthritis: Implementation of precision medicine – Or “one size fits all” concept?","authors":"Fabian Proft , Tugba Izci Duran , Kamran Ghoreschi , Uwe Pleyer , Britta Siegmund , Denis Poddubnyy","doi":"10.1016/j.autrev.2024.103638","DOIUrl":"10.1016/j.autrev.2024.103638","url":null,"abstract":"<div><p>Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 10","pages":"Article 103638"},"PeriodicalIF":9.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224001290/pdfft?md5=279fd1308e78f0ff5c869ecedf305247&pid=1-s2.0-S1568997224001290-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1016/j.autrev.2024.103639
Hong Luo
Background
This study aims to describe the global burden trends of six immune-mediated inflammatory diseases (IMIDs), including asthma, atopic dermatitis (AD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis and rheumatoid arthritis (RA), from 1990 to 2021, and analyze patterns of cross-country inequalities.
Methods
The estimates for the number of disability-adjusted life-years (DALYs) and age-standardized DALYs rates (ASDR), along with the 95 % uncertainty intervals (UI) for asthma, AD, IBD, MS, psoriasis and RA, were obtained from the Global Burden of Diseases Study 2021. The estimated annual percentage change (EAPC) was used to quantify the global burden trends of these six IMIDs from 1990 to 2021. Additionally, slope index of inequality and concentration index were employed to quantify the distributional inequalities in the burden of IMIDs.
Results
From 1990 to 2021, the global ASDR of psoriasis (EAPC = 0.23 %, 95 % UI: 0.21 to 0.25) and RA (EAPC = 0.05 %, 95 % UI: 0.01to 0.10) showed an increasing trend, while the global ASDRs of asthma (EAPC = −1.91 %, 95 % UI: −1.98 to −1.84), AD (EAPC = −0.26 %, 95 % UI: −0.27 to −0.26), IBD (EAPC = −0.52 %, 95 % UI: −0.60 to −0.43) and MS (EAPC = −0.39 %, 95 % UI: −0.45 to −0.33) demonstrated declining trends. The cross-country inequality analysis reveals pronounced heterogeneity in the burden of these six IMIDs.
Conclusions
The global distribution of the DALYs burden attributable to IMIDs exhibits significant disparities across regions, underscoring an urgent need for innovative and comprehensive management strategies to address this heterogeneous landscape.
{"title":"Global burden and cross-country inequalities in six major immune-mediated inflammatory diseases from 1990 to 2021: A systemic analysis of the Global Burden of Disease Study 2021","authors":"Hong Luo","doi":"10.1016/j.autrev.2024.103639","DOIUrl":"10.1016/j.autrev.2024.103639","url":null,"abstract":"<div><h3>Background</h3><p>This study aims to describe the global burden trends of six immune-mediated inflammatory diseases (IMIDs), including asthma, atopic dermatitis (AD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis and rheumatoid arthritis (RA), from 1990 to 2021, and analyze patterns of cross-country inequalities.</p></div><div><h3>Methods</h3><p>The estimates for the number of disability-adjusted life-years (DALYs) and age-standardized DALYs rates (ASDR), along with the 95 % uncertainty intervals (UI) for asthma, AD, IBD, MS, psoriasis and RA, were obtained from the Global Burden of Diseases Study 2021. The estimated annual percentage change (EAPC) was used to quantify the global burden trends of these six IMIDs from 1990 to 2021. Additionally, slope index of inequality and concentration index were employed to quantify the distributional inequalities in the burden of IMIDs.</p></div><div><h3>Results</h3><p>From 1990 to 2021, the global ASDR of psoriasis (EAPC = 0.23 %, 95 % UI: 0.21 to 0.25) and RA (EAPC = 0.05 %, 95 % UI: 0.01to 0.10) showed an increasing trend, while the global ASDRs of asthma (EAPC = −1.91 %, 95 % UI: −1.98 to −1.84), AD (EAPC = −0.26 %, 95 % UI: −0.27 to −0.26), IBD (EAPC = −0.52 %, 95 % UI: −0.60 to −0.43) and MS (EAPC = −0.39 %, 95 % UI: −0.45 to −0.33) demonstrated declining trends. The cross-country inequality analysis reveals pronounced heterogeneity in the burden of these six IMIDs.</p></div><div><h3>Conclusions</h3><p>The global distribution of the DALYs burden attributable to IMIDs exhibits significant disparities across regions, underscoring an urgent need for innovative and comprehensive management strategies to address this heterogeneous landscape.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 10","pages":"Article 103639"},"PeriodicalIF":9.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169191","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 : 2024-09-11DOI: 10.1016/j.autrev.2024.103636
Javier Narváez , Martí Aguilar-Coll , Montserrat Roig-Kim , Pol Maymó-Paituvi , Judith Palacios-Olid , Joan Miquel Nolla , Dídac LLop
Objective
The treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains challenging due to the scarcity of proven effective therapeutic options. This study aimed to investigate the effectiveness and safety of Janus kinase inhibitors (JAKi) in RA-ILD.
Methods
We systematically reviewed the literature to identify studies evaluating the efficacy and safety of JAK inhibitors in RA-ILD. A meta-analysis was performed using the random-effects model.
Results
The literature search identified seven observational studies assessing the safety and efficacy of JAKi in RA-ILD and three studies analyzing the risk of developing de novo ILD in RA patients treated with JAKi.
Among 183 patients with RA-ILD, the pooled analysis demonstrated an increase of 2.07 % in %pFVC (95 % CI: 0.57–3.58; p = 0.007) and 3.12 % in %pDLCO (95 % CI: 2.11–4.12; p < 0.001). Thoracic HRCT scans showed improvement in 11 % of patients (95 % CI: 0.01–0.29). The pooled proportion of patients experiencing worsening of pre-existing ILD was 5 % (95 % CI: 0.01–0.11).
Adverse events were reported in 14 % of cases (95 % CI: 0.08–0.21), with the frequency of clinically significant infections ranging from 4.5 % to 25 %.
The risk of developing de novo ILD in patients receiving JAKi was low, with an incidence rate of 0.20 per 1000 person-years (95 % CI: 0.14–0.25). Comparisons with abatacept and rituximab suggested similar efficacy and safety profiles.
Conclusion
JAKi are well tolerated and might be a viable treatment option for RA-ILD, offering comparable safety and efficacy to abatacept and rituximab.
{"title":"Janus kinase inhibitors in rheumatoid arthritis-associated interstitial lung disease: A systematic review and meta-analysis","authors":"Javier Narváez , Martí Aguilar-Coll , Montserrat Roig-Kim , Pol Maymó-Paituvi , Judith Palacios-Olid , Joan Miquel Nolla , Dídac LLop","doi":"10.1016/j.autrev.2024.103636","DOIUrl":"10.1016/j.autrev.2024.103636","url":null,"abstract":"<div><h3>Objective</h3><div>The treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains challenging due to the scarcity of proven effective therapeutic options. This study aimed to investigate the effectiveness and safety of Janus kinase inhibitors (JAKi) in RA-ILD.</div></div><div><h3>Methods</h3><div>We systematically reviewed the literature to identify studies evaluating the efficacy and safety of JAK inhibitors in RA-ILD. A meta-analysis was performed using the random-effects model.</div></div><div><h3>Results</h3><div>The literature search identified seven observational studies assessing the safety and efficacy of JAKi in RA-ILD and three studies analyzing the risk of developing de novo ILD in RA patients treated with JAKi.</div><div>Among 183 patients with RA-ILD, the pooled analysis demonstrated an increase of 2.07 % in %pFVC (95 % CI: 0.57–3.58; <em>p</em> = 0.007) and 3.12 % in %pDLCO (95 % CI: 2.11–4.12; <em>p</em> < 0.001). Thoracic HRCT scans showed improvement in 11 % of patients (95 % CI: 0.01–0.29). The pooled proportion of patients experiencing worsening of pre-existing ILD was 5 % (95 % CI: 0.01–0.11).</div><div>Adverse events were reported in 14 % of cases (95 % CI: 0.08–0.21), with the frequency of clinically significant infections ranging from 4.5 % to 25 %.</div><div>The risk of developing de novo ILD in patients receiving JAKi was low, with an incidence rate of 0.20 per 1000 person-years (95 % CI: 0.14–0.25). Comparisons with abatacept and rituximab suggested similar efficacy and safety profiles.</div></div><div><h3>Conclusion</h3><div>JAKi are well tolerated and might be a viable treatment option for RA-ILD, offering comparable safety and efficacy to abatacept and rituximab.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 10","pages":"Article 103636"},"PeriodicalIF":9.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279913","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 : 2024-09-08DOI: 10.1016/j.autrev.2024.103637
Rosanna Campitiello , Stefano Soldano , Emanuele Gotelli , Elvis Hysa , Paola Montagna , Andrea Casabella , Sabrina Paolino , Carmen Pizzorni , Alberto Sulli , Vanessa Smith , Maurizio Cutolo
<div><h3>Background and aim</h3><p>Systemic sclerosis (SSc) is an immune mediated connective tissue disease characterized by microvascular dysfunction, aberrant immune response, and progressive fibrosis. Although the immuno-pathophysiological mechanisms underlying SSc are not fully clarified, they are often associated with a dysfunctional macrophage activation toward an alternative (M2) phenotype induced by cytokines [<em>i.e.</em>, IL-4, IL-10, IL-13, and transforming growth factor (TGF-β)] involved in the fibrotic and anti-inflammatory process. A spectrum of macrophage activation state has been identified ranging from M1 to M2 phenotype, gene expression of phenotype markers, and functional aspects. This systematic review aims to analyze the importance of M2 macrophage polatization during the immune mediated process and the identification of specific pathways, cytokines, and chemokines involved in SSc pathogenesis. Moreover, this review provides an overview on the <em>in vitro</em> and <em>in vivo</em> studies aiming to test therapeutic strategies targeting M2 macrophages.</p></div><div><h3>Methods</h3><p>A systematic literature review was performed according to the preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA). The search encompassed the online medical databases PubMed and Embase up to the 30th of June 2024. Original research manuscripts (<em>in vitro</em> study, <em>in vivo</em> study), animal model and human cohort<del>,</del> were considered for the review. Exclusion criteria encompassed reviews, case reports, correspondences, and conference abstracts/posters. The eligible manuscripts main findings were critically analyzed, discussed, and summarized in the correspondent tables.</p></div><div><h3>Results</h3><p>Out of the 77 screened abstracts, 49 papers were deemed eligible. Following a critical analysis, they were categorized according to the primary (29 original articles) and secondary (20 original articles) research objectives of this systematic review. The data from the present systematic review suggest the pivotal role of M2 macrophages differentiation and activation together with the dysregulation of the immune system in the SSc pathogenesis. Strong correlations have been found between M2 macrophage presence and clinical manifestations in both murine and human tissue samples. Interestingly, the presence of M2 cell surface markers on peripheral blood monocytes has been highlighted, suggesting a potential biomarker role for this finding. Therapeutic effects reducing M2 macrophage activities have been observed and/or tested for existing and for new drugs, demonstrating potential efficacy in modulating the pro-fibrotic immune response for treatment of SSc.</p></div><div><h3>Conclusions</h3><p>The increased M2 macrophage activation in course of SSc seems to offer new insights on the self-amplifying inflammatory and fibrotic response by the immune system on such disease. Therefore, the revaluation of immunomodula
{"title":"The intervention of macrophages in progressive fibrosis characterizing systemic sclerosis: A systematic review","authors":"Rosanna Campitiello , Stefano Soldano , Emanuele Gotelli , Elvis Hysa , Paola Montagna , Andrea Casabella , Sabrina Paolino , Carmen Pizzorni , Alberto Sulli , Vanessa Smith , Maurizio Cutolo","doi":"10.1016/j.autrev.2024.103637","DOIUrl":"10.1016/j.autrev.2024.103637","url":null,"abstract":"<div><h3>Background and aim</h3><p>Systemic sclerosis (SSc) is an immune mediated connective tissue disease characterized by microvascular dysfunction, aberrant immune response, and progressive fibrosis. Although the immuno-pathophysiological mechanisms underlying SSc are not fully clarified, they are often associated with a dysfunctional macrophage activation toward an alternative (M2) phenotype induced by cytokines [<em>i.e.</em>, IL-4, IL-10, IL-13, and transforming growth factor (TGF-β)] involved in the fibrotic and anti-inflammatory process. A spectrum of macrophage activation state has been identified ranging from M1 to M2 phenotype, gene expression of phenotype markers, and functional aspects. This systematic review aims to analyze the importance of M2 macrophage polatization during the immune mediated process and the identification of specific pathways, cytokines, and chemokines involved in SSc pathogenesis. Moreover, this review provides an overview on the <em>in vitro</em> and <em>in vivo</em> studies aiming to test therapeutic strategies targeting M2 macrophages.</p></div><div><h3>Methods</h3><p>A systematic literature review was performed according to the preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA). The search encompassed the online medical databases PubMed and Embase up to the 30th of June 2024. Original research manuscripts (<em>in vitro</em> study, <em>in vivo</em> study), animal model and human cohort<del>,</del> were considered for the review. Exclusion criteria encompassed reviews, case reports, correspondences, and conference abstracts/posters. The eligible manuscripts main findings were critically analyzed, discussed, and summarized in the correspondent tables.</p></div><div><h3>Results</h3><p>Out of the 77 screened abstracts, 49 papers were deemed eligible. Following a critical analysis, they were categorized according to the primary (29 original articles) and secondary (20 original articles) research objectives of this systematic review. The data from the present systematic review suggest the pivotal role of M2 macrophages differentiation and activation together with the dysregulation of the immune system in the SSc pathogenesis. Strong correlations have been found between M2 macrophage presence and clinical manifestations in both murine and human tissue samples. Interestingly, the presence of M2 cell surface markers on peripheral blood monocytes has been highlighted, suggesting a potential biomarker role for this finding. Therapeutic effects reducing M2 macrophage activities have been observed and/or tested for existing and for new drugs, demonstrating potential efficacy in modulating the pro-fibrotic immune response for treatment of SSc.</p></div><div><h3>Conclusions</h3><p>The increased M2 macrophage activation in course of SSc seems to offer new insights on the self-amplifying inflammatory and fibrotic response by the immune system on such disease. Therefore, the revaluation of immunomodula","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 10","pages":"Article 103637"},"PeriodicalIF":9.2,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224001289/pdfft?md5=0a912fc4418a6e852931c6e499992eaf&pid=1-s2.0-S1568997224001289-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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