Pub Date : 2025-07-14DOI: 10.1016/j.autrev.2025.103876
Jin Lin , Fan Yang , Yanyi Zheng , Xianglin Wang , Xiaoli Fan , Li Yang
Autoimmune diseases (ADs) are a classification of disorders that occur owing to the breakdown of immunological tolerance to self-antigens, leading to an immune response to these antigens and associated bodily harm. The pathogenesis and etiology of these diseases remain unclear. A growing body of research indicates that metabolic reprogramming of immune cells is crucial for immunological control. In particular, glycolysis, a crucial metabolic process in cells, is reconfigured to influence the phenotypic and function of immune cells, therefore playing a role in the onset and progression of ADs. This review elaborates on the involvement of glycometabolic reprogramming in ADs and explores the function of glycometabolic reprogramming in immune cells throughout disease progression. Furthermore, we examine the principal targets implicated and their influence on disease advancement. Finally, we provide a brief summary and outlook of studies related to glycometabolic reprogramming of immune cells in ADs, aiming to guide therapeutic strategies for these diseases.
{"title":"Glycometabolic reprogramming of immune cells in autoimmune diseases","authors":"Jin Lin , Fan Yang , Yanyi Zheng , Xianglin Wang , Xiaoli Fan , Li Yang","doi":"10.1016/j.autrev.2025.103876","DOIUrl":"10.1016/j.autrev.2025.103876","url":null,"abstract":"<div><div>Autoimmune diseases (ADs) are a classification of disorders that occur owing to the breakdown of immunological tolerance to self-antigens, leading to an immune response to these antigens and associated bodily harm. The pathogenesis and etiology of these diseases remain unclear. A growing body of research indicates that metabolic reprogramming of immune cells is crucial for immunological control. In particular, glycolysis, a crucial metabolic process in cells, is reconfigured to influence the phenotypic and function of immune cells, therefore playing a role in the onset and progression of ADs. This review elaborates on the involvement of glycometabolic reprogramming in ADs and explores the function of glycometabolic reprogramming in immune cells throughout disease progression. Furthermore, we examine the principal targets implicated and their influence on disease advancement. Finally, we provide a brief summary and outlook of studies related to glycometabolic reprogramming of immune cells in ADs, aiming to guide therapeutic strategies for these diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103876"},"PeriodicalIF":9.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648353","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 : 2025-07-14DOI: 10.1016/j.autrev.2025.103879
Nantakarn Pongtarakulpanit , Shiri Keret , Vaidehi Kothari , Francisca Bozán , Chengappa Kavadichanda , Akira Yoshida , Valérie Leclair , Anuradha Bishnoi , Kaveh Ardalan , Edoardo Conticini , Ting-Yuan Lan , Océane Landon-Cardinal , Iris Y.K. Tang , Silvia Rosina , Belina Y. Yi , James B. Lilleker , Eduardo Dourado , Prateek C. Gandiga , Rohit Aggarwal
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare systemic autoimmune rheumatic diseases. Despite advances in treatment, the definition of remission and low disease activity (LDA) in IIM remains inconsistent and lacks consensus and validation. This review summarizes existing published definitions, achievement rates, and predictive factors of remission/LDA in adult IIM, focusing on dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathies (IMNM). Our literature review revealed a wide variability in remission definitions, incorporating physician assessment, muscle strength, laboratory normalization, and medication tapering or discontinuation. Some studies defined “remission on medication”, while others required complete treatment cessation. Most definitions required a minimum duration of six months. Organ-specific remission (including for the skin, lung, and muscle domains) was inconsistently addressed. LDA has been less extensively studied in IIM, with the myositis disease activity assessment visual analog scales (MYOACT) being the only measure applied to DM. Remission rates varied widely, with stricter criteria yielding lower rates. Factors associated with remission included younger age, early immunosuppressive treatment, non-severe muscle involvement, the absence of myositis-specific autoantibodies (MSA), although some studies reported positivity for certain MSA were associated with remission. Conversely, remission was less likely for patients with PM, overlap myositis, and those positive for anti-TIF1-γ or Ku autoantibodies. Standardized remission criteria incorporating physician assessment, patient assessment, organ-specific parameters, laboratory assessments, and sustained remission duration are essential for harmonizing clinical and research evaluations in IIM. Establishing uniform definitions will improve therapeutic outcome assessments and facilitate meaningful comparisons in clinical trials and real-world practice.
{"title":"Remission and low disease activity definitions in adult idiopathic inflammatory myopathies: A narrative review by myositis clinical trials consortium (MCTC)","authors":"Nantakarn Pongtarakulpanit , Shiri Keret , Vaidehi Kothari , Francisca Bozán , Chengappa Kavadichanda , Akira Yoshida , Valérie Leclair , Anuradha Bishnoi , Kaveh Ardalan , Edoardo Conticini , Ting-Yuan Lan , Océane Landon-Cardinal , Iris Y.K. Tang , Silvia Rosina , Belina Y. Yi , James B. Lilleker , Eduardo Dourado , Prateek C. Gandiga , Rohit Aggarwal","doi":"10.1016/j.autrev.2025.103879","DOIUrl":"10.1016/j.autrev.2025.103879","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare systemic autoimmune rheumatic diseases. Despite advances in treatment, the definition of remission and low disease activity (LDA) in IIM remains inconsistent and lacks consensus and validation. This review summarizes existing published definitions, achievement rates, and predictive factors of remission/LDA in adult IIM, focusing on dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathies (IMNM). Our literature review revealed a wide variability in remission definitions, incorporating physician assessment, muscle strength, laboratory normalization, and medication tapering or discontinuation. Some studies defined “remission on medication”, while others required complete treatment cessation. Most definitions required a minimum duration of six months. Organ-specific remission (including for the skin, lung, and muscle domains) was inconsistently addressed. LDA has been less extensively studied in IIM, with the myositis disease activity assessment visual analog scales (MYOACT) being the only measure applied to DM. Remission rates varied widely, with stricter criteria yielding lower rates. Factors associated with remission included younger age, early immunosuppressive treatment, non-severe muscle involvement, the absence of myositis-specific autoantibodies (MSA), although some studies reported positivity for certain MSA were associated with remission. Conversely, remission was less likely for patients with PM, overlap myositis, and those positive for anti-TIF1-γ or Ku autoantibodies. Standardized remission criteria incorporating physician assessment, patient assessment, organ-specific parameters, laboratory assessments, and sustained remission duration are essential for harmonizing clinical and research evaluations in IIM. Establishing uniform definitions will improve therapeutic outcome assessments and facilitate meaningful comparisons in clinical trials and real-world practice.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103879"},"PeriodicalIF":9.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648354","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 : 2025-07-14DOI: 10.1016/j.autrev.2025.103878
Xuhong Zhang, Lu Jia, Xueni Lin, Lamei Zhou
Ankylosing spondylitis (AS) is a chronic immune-mediated disorder defined by the paradoxical coupling of inflammatory bone erosion and ectopic new bone formation. Recent studies implicate the Forkhead box O1 (FOXO1)-Sirtuin 1 (SIRT1) signaling axis as a systems-level regulator integrating immune metabolism, redox balance, and skeletal remodeling. FOXO1 and SIRT1 cooperatively regulate immune tolerance, redox balance, and skeletal homeostasis via transcriptional, epigenetic, and metabolic pathways.
This review delineates the cross-platform roles of the FOXO1-SIRT1 axis across three interrelated modules: regulation of immune cell metabolism and polarization; redox sensing and organelle quality control via autophagy and mitophagy; and coordination of osteoblast – osteoclast dynamics in inflammatory microenvironments. Dysregulation of this axis disrupts immuno-metabolic equilibrium and promotes pathological ossification, contributing to the dual pathology of AS.
We further discuss emerging therapeutic strategies – ranging from SIRT1 activators and anti -Interleukin-17 A (IL-17 A) biologics to histone deacetylase inhibitors – that converge mechanistically on FOXO1-SIRT1 signaling. These translational approaches underscore the axis's potential as a cross-domain integrator of immune and skeletal homeostasis, and as a promising target for precision intervention in AS.
强直性脊柱炎（AS）是一种慢性免疫介导的疾病，由炎症性骨侵蚀和异位新骨形成的矛盾耦合所定义。最近的研究表明叉头盒O1 (FOXO1)- SIRT1 （SIRT1）信号轴是一个系统水平的调节因子，整合了免疫代谢、氧化还原平衡和骨骼重塑。FOXO1和SIRT1通过转录、表观遗传和代谢途径协同调节免疫耐受、氧化还原平衡和骨骼稳态。本文综述了fox01 - sirt1轴在三个相互关联的模块中的跨平台作用：免疫细胞代谢和极化的调节；自噬和有丝自噬的氧化还原传感和细胞器质量控制炎症微环境中成骨细胞-破骨细胞动力学的协调。该轴的失调破坏免疫代谢平衡，促进病理性骨化，导致AS的双重病理。我们进一步讨论了新兴的治疗策略，从SIRT1激活剂和抗白细胞介素-17 A （IL-17 A）生物制剂到组蛋白去乙酰化酶抑制剂，它们在机制上聚集在fox01 -SIRT1信号传导上。这些翻译方法强调了轴作为免疫和骨骼动态平衡的跨域整合器的潜力，以及作为精确干预as的有希望的靶点。
{"title":"The FOXO1-SIRT1 axis in ankylosing spondylitis: A cross-platform regulator linking immunometabolism, oxidative stress, and bone remodeling","authors":"Xuhong Zhang, Lu Jia, Xueni Lin, Lamei Zhou","doi":"10.1016/j.autrev.2025.103878","DOIUrl":"10.1016/j.autrev.2025.103878","url":null,"abstract":"<div><div>Ankylosing spondylitis (AS) is a chronic immune-mediated disorder defined by the paradoxical coupling of inflammatory bone erosion and ectopic new bone formation. Recent studies implicate the Forkhead box O1 (FOXO1)-Sirtuin 1 (SIRT1) signaling axis as a systems-level regulator integrating immune metabolism, redox balance, and skeletal remodeling. FOXO1 and SIRT1 cooperatively regulate immune tolerance, redox balance, and skeletal homeostasis via transcriptional, epigenetic, and metabolic pathways.</div><div>This review delineates the cross-platform roles of the FOXO1-SIRT1 axis across three interrelated modules: regulation of immune cell metabolism and polarization; redox sensing and organelle quality control via autophagy and mitophagy; and coordination of osteoblast – osteoclast dynamics in inflammatory microenvironments. Dysregulation of this axis disrupts immuno-metabolic equilibrium and promotes pathological ossification, contributing to the dual pathology of AS.</div><div>We further discuss emerging therapeutic strategies – ranging from SIRT1 activators and anti -Interleukin-17 A (IL-17 A) biologics to histone deacetylase inhibitors – that converge mechanistically on FOXO1-SIRT1 signaling. These translational approaches underscore the axis's potential as a cross-domain integrator of immune and skeletal homeostasis, and as a promising target for precision intervention in AS.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103878"},"PeriodicalIF":9.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648355","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 : 2025-07-10DOI: 10.1016/j.autrev.2025.103875
M. Mané-Damas , A.K. Schöttler , F. Marcuse , P.C. Molenaar , T. Mohile , J.G.J. Hoeijmakers , M. Hochstenbag , J. Damoiseaux , J.G. Maessen , M. Abdul-Hamid , A. zur Hausen , M.H. de Baets , M. Losen , P. Martinez-Martinez
Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder where the neuromuscular transmission is impaired, causing symptoms of skeletal muscle weakness and fatigue. The presence of autoantibodies against the muscle nicotinic acetylcholine receptor (AChR) is the most prevalent cause of MG. Abnormalities in the thymus are common in AChR-MG, and thymectomy has proven to be therapeutically beneficial. Up to 30 % of AChR-MG patients have also thymoma. Moreover, patients with thymoma without MG are more prompt to develop MG compared to the general population.
Autoantibodies in AChR-MG damage the postsynaptic membrane of the neuromuscular junction (NMJ) and cause muscle weakness by impairing synaptic transmission because of the depletion of the AChRs and destruction of the NMJ. The pathogenic autoantibody levels vary greatly between patients. In contrast, in individual patients changes in autoantibody levels correlate well with disease severity. A small selection of patients has been used to exemplify the individual relationship between autoantibody levels and disease progression. The study of the effector functions of the autoantibodies and the compensatory mechanisms at the NMJ are important to select the best treatment strategy for each patient. Even though classical immunomodulatory treatments are effective in many patients, around 10–20 % of patients do not respond to current therapies. This may be attributed to the production of autoantibodies by different circulating cells including mature B and long-lived plasma cells, which are resistant to most commonly used immunosuppressive drugs. Hence, novel therapies specifically targeting plasma cells might be a suitable therapeutic approach for selected refractory patients.
{"title":"Myasthenia gravis with antibodies against the AChR, current knowledge on pathophysiology and an update on treatment strategies with special focus on targeting plasma cells","authors":"M. Mané-Damas , A.K. Schöttler , F. Marcuse , P.C. Molenaar , T. Mohile , J.G.J. Hoeijmakers , M. Hochstenbag , J. Damoiseaux , J.G. Maessen , M. Abdul-Hamid , A. zur Hausen , M.H. de Baets , M. Losen , P. Martinez-Martinez","doi":"10.1016/j.autrev.2025.103875","DOIUrl":"10.1016/j.autrev.2025.103875","url":null,"abstract":"<div><div>Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder where the neuromuscular transmission is impaired, causing symptoms of skeletal muscle weakness and fatigue. The presence of autoantibodies against the muscle nicotinic acetylcholine receptor (AChR) is the most prevalent cause of MG. Abnormalities in the thymus are common in AChR-MG, and thymectomy has proven to be therapeutically beneficial. Up to 30 % of AChR-MG patients have also thymoma. Moreover, patients with thymoma without MG are more prompt to develop MG compared to the general population.</div><div>Autoantibodies in AChR-MG damage the postsynaptic membrane of the neuromuscular junction (NMJ) and cause muscle weakness by impairing synaptic transmission because of the depletion of the AChRs and destruction of the NMJ. The pathogenic autoantibody levels vary greatly between patients. In contrast, in individual patients changes in autoantibody levels correlate well with disease severity. A small selection of patients has been used to exemplify the individual relationship between autoantibody levels and disease progression. The study of the effector functions of the autoantibodies and the compensatory mechanisms at the NMJ are important to select the best treatment strategy for each patient. Even though classical immunomodulatory treatments are effective in many patients, around 10–20 % of patients do not respond to current therapies. This may be attributed to the production of autoantibodies by different circulating cells including mature B and long-lived plasma cells, which are resistant to most commonly used immunosuppressive drugs. Hence, novel therapies specifically targeting plasma cells might be a suitable therapeutic approach for selected refractory patients.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103875"},"PeriodicalIF":9.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616106","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 : 2025-07-08DOI: 10.1016/j.autrev.2025.103872
Yuezheng Xiao , Yue Xin , Kai Shen , Ming Yang , Haijing Wu
The transient receptor potential vanilloid (TRPV) is a family of tetrameric cation channels, expressed in various tissues and cell types. It includes thermosensitive isoforms (TRPV1–4) and calcium-permeable members (TRPV5–6). In the context of autoimmune diseases, TRPV channels have been firmly established as pivotal regulators that bridge changes in the cellular environment to the immune system.
Originally identified for their roles in thermosensation and nociception, these polymodal sensors have now emerged as crucial determinants of immune cell function. They are capable of converting chemical signals, temperature fluctuations, and mechanical forces into calcium-mediated signal transduction pathways. Mounting evidence indicates that dysregulated TRPV channel activity leads to pathological calcium influx, triggering a signaling cascade that reprograms the functions of key immune cells and modulates pain and itch signaling through neuroimmune crosstalk. These cascades amplify inflammatory responses, exacerbate autoimmune pathology, promote inflammatory cytokine release, and modulate pain/itch signaling via neuroimmune crosstalk.
Specifically, these mechanisms are instrumental in the progression including autoimmune disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), multiple sclerosis (MS), psoriasis, and atopic dermatitis (AD). Novel therapeutic strategies are emerging, aiming to modulate TRPV activity in autoimmune conditions. Approaches include suppressing hyperactive channels and leveraging their immunoregulatory potential. Promising preclinical results have highlighted that TRPV channels exhibit dual translational potential in mechanistic research of autoimmune diseases, integrating precise targeting with dynamic monitoring capabilities. However, translating these findings into clinical applications faces significant challenges, including differential effects on neuronal and immune signaling, as well as systemic side effects caused by disruptions to physiological homeostasis.
This narrative review discuss how TRPV channel signaling has enhanced our understanding of autoimmune disease initiation. By dissecting how TRPV-mediated immune dysregulation drives pathological immune responses, we seek to offer novel mechanistic insights to inform the development of more effective and comprehensive treatment strategies for autoimmune diseases.
{"title":"The roles of transient receptor potential vanilloid in autoimmune diseases","authors":"Yuezheng Xiao , Yue Xin , Kai Shen , Ming Yang , Haijing Wu","doi":"10.1016/j.autrev.2025.103872","DOIUrl":"10.1016/j.autrev.2025.103872","url":null,"abstract":"<div><div>The transient receptor potential vanilloid (TRPV) is a family of tetrameric cation channels, expressed in various tissues and cell types. It includes thermosensitive isoforms (TRPV1–4) and calcium-permeable members (TRPV5–6). In the context of autoimmune diseases, TRPV channels have been firmly established as pivotal regulators that bridge changes in the cellular environment to the immune system.</div><div>Originally identified for their roles in thermosensation and nociception, these polymodal sensors have now emerged as crucial determinants of immune cell function. They are capable of converting chemical signals, temperature fluctuations, and mechanical forces into calcium-mediated signal transduction pathways. Mounting evidence indicates that dysregulated TRPV channel activity leads to pathological calcium influx, triggering a signaling cascade that reprograms the functions of key immune cells and modulates pain and itch signaling through neuroimmune crosstalk. These cascades amplify inflammatory responses, exacerbate autoimmune pathology, promote inflammatory cytokine release, and modulate pain/itch signaling via neuroimmune crosstalk.</div><div>Specifically, these mechanisms are instrumental in the progression including autoimmune disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), multiple sclerosis (MS), psoriasis, and atopic dermatitis (AD). Novel therapeutic strategies are emerging, aiming to modulate TRPV activity in autoimmune conditions. Approaches include suppressing hyperactive channels and leveraging their immunoregulatory potential. Promising preclinical results have highlighted that TRPV channels exhibit dual translational potential in mechanistic research of autoimmune diseases, integrating precise targeting with dynamic monitoring capabilities. However, translating these findings into clinical applications faces significant challenges, including differential effects on neuronal and immune signaling, as well as systemic side effects caused by disruptions to physiological homeostasis.</div><div>This narrative review discuss how TRPV channel signaling has enhanced our understanding of autoimmune disease initiation. By dissecting how TRPV-mediated immune dysregulation drives pathological immune responses, we seek to offer novel mechanistic insights to inform the development of more effective and comprehensive treatment strategies for autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103872"},"PeriodicalIF":9.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607262","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}
Dysregulation of circulating follicular helper T (cTfh) cells plays a key role in the breakdown of immune tolerance and the pathogenesis of antibody-mediated autoimmune diseases, including systemic lupus erythematosus (SLE). This study aims to evaluate the proportions of cTfh cells and their potential pathogenic mechanisms in the peripheral blood of SLE patients through a systematic review and meta-analysis.
Methods
Systematic search and review were conducted across PubMed, Cochrane Library, EMBASE, and Web of Science to identify relevant studies. A meta-analysis was performed to compare the proportions of cTfh cells and their subsets between SLE patients and healthy controls (HC). Subgroup analyses were conducted based on the markers used for defining cTfh cells and geographical regions.
Results
The meta-analysis revealed a significantly higher proportion of cTfh cells in SLE patients compared to HC (SMD 0.904, [0.620, 1.188], p < 0.01). Subgroup analyses showed a consistent increase in cTfh cells in SLE across different markers. Geographically, both Asian (SMD 1.005, [0.608, 1.402], p < 0.01) and non-Asian populations (SMD 0.708, [0.428, 0.988], p < 0.01) demonstrated elevated cTfh cell proportions in SLE. A trend toward a decrease in Tfh1 cells and an increase in Tfh17 cells was observed, though neither reached statistical significance.
Conclusion
Our study demonstrates that cTfh cells proportions are significantly elevated in SLE patients, supporting their role in the pathogenesis of SLE. These findings suggest that cTfh cells could serve as potential biomarkers for SLE and therapeutic targets for treatment.
目的：循环滤泡辅助性T细胞（cTfh）的失调在免疫耐受的破坏和抗体介导的自身免疫性疾病（包括系统性红斑狼疮（SLE））的发病机制中起着关键作用。本研究旨在通过系统综述和荟萃分析，评估cTfh细胞在SLE患者外周血中的比例及其潜在致病机制。方法通过PubMed、Cochrane Library、EMBASE和Web of Science进行系统检索和综述，确定相关研究。进行了一项荟萃分析，比较SLE患者和健康对照（HC）之间cTfh细胞及其亚群的比例。根据用于定义cTfh细胞和地理区域的标记物进行亚组分析。结果荟萃分析显示，SLE患者中cTfh细胞的比例明显高于HC (SMD = 0.904, [0.620, 1.188], p <；0.01)。亚组分析显示，不同标记的SLE患者cTfh细胞一致增加。地理上，亚洲(SMD 1.005, [0.608, 1.402], p <；0.01)和非亚洲人群(SMD = 0.708, [0.428, 0.988], p <；0.01)表明cTfh细胞比例在SLE中升高。Tfh1细胞呈减少趋势，Tfh17细胞呈增加趋势，但均未达到统计学意义。结论cTfh细胞比例在SLE患者中显著升高，支持其在SLE发病机制中的作用。这些发现表明cTfh细胞可以作为SLE的潜在生物标志物和治疗靶点。
{"title":"Proportion of circulating T follicular helper cells in peripheral blood of systemic lupus erythematosus patients: A systematic review and meta-analysis","authors":"Futai Feng , Ziyan Wu , Honglin Xu , Yongzhe Li , Shulan Zhang","doi":"10.1016/j.autrev.2025.103874","DOIUrl":"10.1016/j.autrev.2025.103874","url":null,"abstract":"<div><h3>Objectives</h3><div>Dysregulation of circulating follicular helper T (cTfh) cells plays a key role in the breakdown of immune tolerance and the pathogenesis of antibody-mediated autoimmune diseases, including systemic lupus erythematosus (SLE). This study aims to evaluate the proportions of cTfh cells and their potential pathogenic mechanisms in the peripheral blood of SLE patients through a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>Systematic search and review were conducted across PubMed, Cochrane Library, EMBASE, and Web of Science to identify relevant studies. A meta-analysis was performed to compare the proportions of cTfh cells and their subsets between SLE patients and healthy controls (HC). Subgroup analyses were conducted based on the markers used for defining cTfh cells and geographical regions.</div></div><div><h3>Results</h3><div>The meta-analysis revealed a significantly higher proportion of cTfh cells in SLE patients compared to HC (SMD 0.904, [0.620, 1.188], <em>p</em> < 0.01). Subgroup analyses showed a consistent increase in cTfh cells in SLE across different markers. Geographically, both Asian (SMD 1.005, [0.608, 1.402], <em>p</em> < 0.01) and non-Asian populations (SMD 0.708, [0.428, 0.988], <em>p</em> < 0.01) demonstrated elevated cTfh cell proportions in SLE. A trend toward a decrease in Tfh1 cells and an increase in Tfh17 cells was observed, though neither reached statistical significance.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that cTfh cells proportions are significantly elevated in SLE patients, supporting their role in the pathogenesis of SLE. These findings suggest that cTfh cells could serve as potential biomarkers for SLE and therapeutic targets for treatment.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103874"},"PeriodicalIF":9.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596604","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 : 2025-07-07DOI: 10.1016/j.autrev.2025.103873
Yuhui Zhao , Weilu Cui , Yayun Han , Minjing Chang
{"title":"Trends in rheumatoid arthritis among U.S. women aged 20 to 44 years, 2001 to 2023","authors":"Yuhui Zhao , Weilu Cui , Yayun Han , Minjing Chang","doi":"10.1016/j.autrev.2025.103873","DOIUrl":"10.1016/j.autrev.2025.103873","url":null,"abstract":"","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 9","pages":"Article 103873"},"PeriodicalIF":9.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587504","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 : 2025-07-07DOI: 10.1016/j.autrev.2025.103865
Angeliki Zoi Lignou , Konstantinos D. Vassilakis , Xenofon Baraliakos , Petros P. Sfikakis , Jacques-Eric Gottenberg , George E. Fragoulis
Background
Immune-mediated inflammatory diseases (IMID) include rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), Crohn's disease (CD), ulcerative colitis (UC), and psoriasis (PsO). While biologic (b) and targeted synthetic (ts) DMARDs are effective, nearly 60 % of patients fail to achieve low disease activity status. Combination targeted therapy (CTT) using concomitantly two different b- or ts-DMARDs has been explored, but results on safety and efficacy are unclear.
Objective
To systematically review the literature on CTT in IMID.
Methods
Following the PICO framework, we included literature of adult patients (≥18 years) with IMID receiving CTT. Three databases (PubMed, Scopus, Epistemonikos) were searched up to June 2024. Studies in non-English, pediatric populations, and non-approved treatments were excluded. Risk of bias was assessed using approved tools.
Results
Of 2038 records, 70 studies (6 RCTs, 11 cohorts, 22 case series, 31 case reports) involving 1200 patients were analyzed. About 75 % of them demonstrated low risk of bias. The most studied combinations were TNFi+IL/23i, JAKi+bDMARDs, and vedolizumab+TNFi. Approximately 40-60 % of patients with PsA, axSpA, and IBD with refractory disease improved with TNFi+IL/23i CTT. About half of patients with inflammatory arthritis and up to 80 % of IBD cases benefited with JAKi+bDMARD CTT, whereas favorable outcomes were observed in 30-50 % of IBD patients following Vedolizumab+TNFi CTT. Safety profiles were generally acceptable, without emerging signals so far.
Conclusion
CTT benefits about half of refractory IMID patients, particularly TNFi/IL-23i, JAKi/bDMARD, and vedolizumab/TNFi combinations, without raising significant safety issues. Further research is needed to clarify safety and efficacy across diseases.
{"title":"Combination targeted therapy with two biologic/targeted synthetic DMARDs in 1200 patients with immune mediated inflammatory diseases. A systematic literature review for current landscape in safety and efficacy","authors":"Angeliki Zoi Lignou , Konstantinos D. Vassilakis , Xenofon Baraliakos , Petros P. Sfikakis , Jacques-Eric Gottenberg , George E. Fragoulis","doi":"10.1016/j.autrev.2025.103865","DOIUrl":"10.1016/j.autrev.2025.103865","url":null,"abstract":"<div><h3>Background</h3><div>Immune-mediated inflammatory diseases (IMID) include rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), Crohn's disease (CD), ulcerative colitis (UC), and psoriasis (PsO). While biologic (b) and targeted synthetic (ts) DMARDs are effective, nearly 60 % of patients fail to achieve low disease activity status. Combination targeted therapy (CTT) using concomitantly two different b- or ts-DMARDs has been explored, but results on safety and efficacy are unclear.</div></div><div><h3>Objective</h3><div>To systematically review the literature on CTT in IMID.</div></div><div><h3>Methods</h3><div>Following the PICO framework, we included literature of adult patients (≥18 years) with IMID receiving CTT. Three databases (PubMed, Scopus, Epistemonikos) were searched up to June 2024. Studies in non-English, pediatric populations, and non-approved treatments were excluded. Risk of bias was assessed using approved tools.</div></div><div><h3>Results</h3><div>Of 2038 records, 70 studies (6 RCTs, 11 cohorts, 22 case series, 31 case reports) involving 1200 patients were analyzed. About 75 % of them demonstrated low risk of bias. The most studied combinations were TNFi+IL/23i, JAKi+bDMARDs, and vedolizumab+TNFi. Approximately 40-60 % of patients with PsA, axSpA, and IBD with refractory disease improved with TNFi+IL/23i CTT. About half of patients with inflammatory arthritis and up to 80 % of IBD cases benefited with JAKi+bDMARD CTT, whereas favorable outcomes were observed in 30-50 % of IBD patients following Vedolizumab+TNFi CTT. Safety profiles were generally acceptable, without emerging signals so far.</div></div><div><h3>Conclusion</h3><div>CTT benefits about half of refractory IMID patients, particularly TNFi/IL-23i, JAKi/bDMARD, and vedolizumab/TNFi combinations, without raising significant safety issues. Further research is needed to clarify safety and efficacy across diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 10","pages":"Article 103865"},"PeriodicalIF":9.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599234","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 : 2025-07-03DOI: 10.1016/j.autrev.2025.103864
Emre Bilgin , Vincenzo Venerito , Dimitrios P. Bogdanos
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have improved the management of type 2 diabetes and obesity. Increasing evidence suggests their potential therapeutic role in rheumatic and musculoskeletal diseases, yet their precise mechanisms and clinical implications remain under investigation. This scoping review evaluates the current evidence on GLP-1 RAs in inflammatory arthritis, osteoarthritis, systemic autoimmune diseases, and other rheumatic conditions. This systematic literature search followed PRISMA-ScR guidelines and identified 52 studies and seven clinical trials from Scopus, PubMed, and ClinicalTrials.gov. Although most of the included studies had a risk of bias, the findings suggest that GLP-1 RAs may influence inflammatory pathways, oxidative stress, and immune regulation in conditions such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), osteoarthritis (OA), and gout. In RA and PsA, GLP-1 RAs have demonstrated potential disease-modifying effects, reducing inflammatory cytokine expression and improving metabolic parameters; however, their clinical impact remains partially linked to weight loss. Studies on OA indicate chondroprotective and anti-inflammatory properties, yet their effect on disease progression remains inconclusive.
Additionally, GLP-1 RAs have been associated with cardiovascular and renal benefits in SLE, though concerns about autoimmune activation persist. Despite promising findings, several challenges remain, including heterogeneous clinical responses, the need for head-to-head comparisons with standard rheumatologic therapies, and a lack of long-term safety data in autoimmune conditions. Drug-induced autoimmune phenomena, cost considerations, and accessibility limitations must be addressed. Future research should focus on distinguishing between metabolic and direct immunomodulatory effects, optimizing combination therapies, and evaluating safety concerns. GLP-1 RAs hold potential as a novel therapeutic approach in rheumatology, but further well-designed randomized controlled trials are essential to establish their clinical role.
{"title":"Glucagon-Like Peptide-1 (GLP-1) receptor agonists in rheumatology: A review of current evidence and future directions","authors":"Emre Bilgin , Vincenzo Venerito , Dimitrios P. Bogdanos","doi":"10.1016/j.autrev.2025.103864","DOIUrl":"10.1016/j.autrev.2025.103864","url":null,"abstract":"<div><div>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have improved the management of type 2 diabetes and obesity. Increasing evidence suggests their potential therapeutic role in rheumatic and musculoskeletal diseases, yet their precise mechanisms and clinical implications remain under investigation. This scoping review evaluates the current evidence on GLP-1 RAs in inflammatory arthritis, osteoarthritis, systemic autoimmune diseases, and other rheumatic conditions. This systematic literature search followed PRISMA-ScR guidelines and identified 52 studies and seven clinical trials from Scopus, PubMed, and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>. Although most of the included studies had a risk of bias, the findings suggest that GLP-1 RAs may influence inflammatory pathways, oxidative stress, and immune regulation in conditions such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), osteoarthritis (OA), and gout. In RA and PsA, GLP-1 RAs have demonstrated potential disease-modifying effects, reducing inflammatory cytokine expression and improving metabolic parameters; however, their clinical impact remains partially linked to weight loss. Studies on OA indicate chondroprotective and anti-inflammatory properties, yet their effect on disease progression remains inconclusive.</div><div>Additionally, GLP-1 RAs have been associated with cardiovascular and renal benefits in SLE, though concerns about autoimmune activation persist. Despite promising findings, several challenges remain, including heterogeneous clinical responses, the need for head-to-head comparisons with standard rheumatologic therapies, and a lack of long-term safety data in autoimmune conditions. Drug-induced autoimmune phenomena, cost considerations, and accessibility limitations must be addressed. Future research should focus on distinguishing between metabolic and direct immunomodulatory effects, optimizing combination therapies, and evaluating safety concerns. GLP-1 RAs hold potential as a novel therapeutic approach in rheumatology, but further well-designed randomized controlled trials are essential to establish their clinical role.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 9","pages":"Article 103864"},"PeriodicalIF":9.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567015","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 : 2025-06-30DOI: 10.1016/j.autrev.2025.103863
Francisco-Josué Cordero-Pérez , Pablo Martínez-Rodríguez , Luis Arribas-Pérez , David Puertas-Miranda , Carlos-Rafael Pires-Baltazar , Leticia Salcedo-Martín , Juan Antonio Sánchez-Villoria , Erik Gabriel Díaz-Ávila , Hugo-Guillermo Ternavasio-De La Vega , Miguel Marcos , Antonio-Javier Chamorro
Background
ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), is a systemic autoimmune disease. This study represents the first large-scale analysis of AAV hospitalisation rates and in-hospital mortality trends in Spain.
Methods
A retrospective longitudinal analysis of AAV-related hospital admissions between 2016 and 2022 was conducted using the ICD-10 codes from the Minimum Basic Dataset (MBDS) of the Spanish National Health System. Statistical analyses were performed, including odds ratios, Student's t-tests, and Mantel-Haenszel trend tests.
Results
Among 5753 AAV episodes, GPA was the most frequent subtype (53.9 %), followed by MPA (31.5 %) and EGPA (14.6 %). AAV episodes were more frequent in older patients (> 65 years) than in other hospital episodes (62.9 % vs. 38.9 %; OR: 2.66, 95 %CI: 2.51–2.80; P < 0.001). Larger hospitals accounted for more AAV episodes, longer hospital stays, and higher costs. MPA had the highest mortality rate (7.2 % vs. 4.9 %; OR: 1.52, 95 % CI: 1.27–1.79; P < 0.001), particularly in patients over 65 years (83.1 % vs. 61.8 %; OR: 3.04, 95 % CI: 2.47–3.75; P < 0.001) compared with the other AAV. In the GPA group, renal involvement significantly increased mortality compared to GPA cases without renal involvement (6.6 % vs. 4.6 %; OR: 1.46, 95 % CI: 1.16–1.83; P = 0.011). Notably, the relative risk of AAV-related deaths increased over the study period (Z = 2.77, P < 0.01).
Conclusion
AAV, particularly MPA, is associated with increased hospital mortality, particularly among older adults and patients with renal involvement.
anca相关性血管炎（AAV），包括肉芽肿病合并多血管炎（GPA）、显微多血管炎（MPA）和嗜酸性肉芽肿病合并多血管炎（EGPA），是一种全身性自身免疫性疾病。该研究首次对西班牙AAV住院率和住院死亡率趋势进行了大规模分析。方法采用西班牙国家卫生系统最低基本数据集（MBDS）的ICD-10代码，对2016 - 2022年aav相关住院病例进行回顾性纵向分析。进行统计分析，包括优势比、学生t检验和Mantel-Haenszel趋势检验。结果5753例AAV发作中，GPA亚型最多（53.9%），MPA亚型次之（31.5%），EGPA亚型次之（14.6%）。AAV发作在老年患者中更为频繁(>；65岁)比其他医院发作(62.9%对38.9%；Or: 2.66, 95% ci: 2.51-2.80；P & lt;0.001)。大型医院的AAV发作次数更多，住院时间更长，费用更高。MPA的死亡率最高(7.2% vs. 4.9%；Or: 1.52, 95% ci: 1.27-1.79；P & lt;0.001)，尤其是65岁以上的患者(83.1% vs. 61.8%；Or: 3.04, 95% ci: 2.47-3.75；P & lt;0.001)，与其他AAV相比。在GPA组中，与没有肾脏受累的GPA患者相比，肾脏受累的死亡率显著增加(6.6% vs. 4.6%；Or: 1.46, 95% ci: 1.16-1.83；p = 0.011)。值得注意的是，在研究期间，aav相关死亡的相对风险增加(Z = 2.77, P <；0.01)。结论：aav，特别是MPA，与医院死亡率增加有关，特别是在老年人和肾脏受累患者中。
{"title":"Epidemiological patterns and in-hospital mortality in ANCA-associated vasculitis: Insights from Spain's National Health Data (2016–2022)","authors":"Francisco-Josué Cordero-Pérez , Pablo Martínez-Rodríguez , Luis Arribas-Pérez , David Puertas-Miranda , Carlos-Rafael Pires-Baltazar , Leticia Salcedo-Martín , Juan Antonio Sánchez-Villoria , Erik Gabriel Díaz-Ávila , Hugo-Guillermo Ternavasio-De La Vega , Miguel Marcos , Antonio-Javier Chamorro","doi":"10.1016/j.autrev.2025.103863","DOIUrl":"10.1016/j.autrev.2025.103863","url":null,"abstract":"<div><h3>Background</h3><div>ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), is a systemic autoimmune disease. This study represents the first large-scale analysis of AAV hospitalisation rates and in-hospital mortality trends in Spain.</div></div><div><h3>Methods</h3><div>A retrospective longitudinal analysis of AAV-related hospital admissions between 2016 and 2022 was conducted using the ICD-10 codes from the Minimum Basic Dataset (MBDS) of the Spanish National Health System. Statistical analyses were performed, including odds ratios, Student's <em>t</em>-tests, and Mantel-Haenszel trend tests.</div></div><div><h3>Results</h3><div>Among 5753 AAV episodes, GPA was the most frequent subtype (53.9 %), followed by MPA (31.5 %) and EGPA (14.6 %). AAV episodes were more frequent in older patients (> 65 years) than in other hospital episodes (62.9 % vs. 38.9 %; OR: 2.66, 95 %CI: 2.51–2.80; <em>P</em> < 0.001). Larger hospitals accounted for more AAV episodes, longer hospital stays, and higher costs. MPA had the highest mortality rate (7.2 % vs. 4.9 %; OR: 1.52, 95 % CI: 1.27–1.79; <em>P</em> < 0.001), particularly in patients over 65 years (83.1 % vs. 61.8 %; OR: 3.04, 95 % CI: 2.47–3.75; <em>P</em> < 0.001) compared with the other AAV. In the GPA group, renal involvement significantly increased mortality compared to GPA cases without renal involvement (6.6 % vs. 4.6 %; OR: 1.46, 95 % CI: 1.16–1.83; <em>P</em> = 0.011). Notably, the relative risk of AAV-related deaths increased over the study period (Z = 2.77, <em>P <</em> 0.01).</div></div><div><h3>Conclusion</h3><div>AAV, particularly MPA, is associated with increased hospital mortality, particularly among older adults and patients with renal involvement.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 9","pages":"Article 103863"},"PeriodicalIF":9.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534506","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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