Clinical and experimental immunology最新文献

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Type I interferon signature: a quantitative standardized method for clinical application. I型干扰素标记:临床应用的定量标准化方法。
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxaf018
Alessandra Tesser, Paola Bocca, Massimo Ulivi, Alessia Pin, Claudia Pastorino, Davide Cangelosi, Elettra Santori, Enrico Drago, Roberta Caorsi, Fabio Candotti, Marco Gattorno, Alberto Tommasini, Stefano Volpi
{"title":"Type I interferon signature: a quantitative standardized method for clinical application.","authors":"Alessandra Tesser, Paola Bocca, Massimo Ulivi, Alessia Pin, Claudia Pastorino, Davide Cangelosi, Elettra Santori, Enrico Drago, Roberta Caorsi, Fabio Candotti, Marco Gattorno, Alberto Tommasini, Stefano Volpi","doi":"10.1093/cei/uxaf018","DOIUrl":"10.1093/cei/uxaf018","url":null,"abstract":"<p><p>Type I Interferon (IFN) induced gene expression analysis (\"IFN signature\") is employed to categorize pathological conditions that exhibit Type I IFN dysregulation and to direct customized therapeutic strategies. For instance, it is used to differentiate patients with IFN-related inflammation from those with conditions primarily mediated by other cytokines, such as juvenile idiopathic arthritis and periodic fevers. Nevertheless, there is currently no standardized method available for clinical practice, and comparing values at different time points or between centers poses a challenge. In this work, we described a standardized method based on the development and validation of a synthetic control to solve the problem of test comparison. Inter-assay and inter-laboratory variability were assessed by multiple repeated analyses within the same laboratory, and between two different laboratories involved in the study. The method has been validated by evaluating the IFN signature of 39 patients with inflammatory disorders known to be related or not to Type I IFN (i.e. monogenic interferonopathies, systemic lupus erythematosus, juvenile dermatomyositis, periodic fevers, and juvenile idiopathic arthritis). The proposed method proved to be highly reproducible among centers and able to discriminate among IFN-related or non-IFN-related inflammation. The use of a synthetic control minimized the inter-assay and inter-laboratory variability, and thus facilitate data sharing among centers to improve knowledge of IFN-related inflammation and patient's care.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From acute lung injury to cerebral ischemia: a unified concept involving intercellular communication through extracellular vesicle-associated miRNAs released by macrophages/microglia. 从急性肺损伤到脑缺血:通过巨噬细胞/小胶质细胞释放的细胞外囊泡相关mirna进行细胞间通讯的统一概念。
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxae105
Xianbin Wang, Ting Wang, Dong Zhu, Jing Wang, Weijie Han
{"title":"From acute lung injury to cerebral ischemia: a unified concept involving intercellular communication through extracellular vesicle-associated miRNAs released by macrophages/microglia.","authors":"Xianbin Wang, Ting Wang, Dong Zhu, Jing Wang, Weijie Han","doi":"10.1093/cei/uxae105","DOIUrl":"10.1093/cei/uxae105","url":null,"abstract":"<p><p>Ischemic stroke and acute lung injury are prevalent life-threatening conditions marked by intricate molecular mechanisms and elevated mortality rates. Despite evident pathophysiological distinctions, a notable similarity exists in the gene responses to tissue injury observed in both pathologies. This similarity extends to both protein-encoding RNAs and non-coding RNAs. Extracellular vesicles (EVs) are nano-scale vesicles derived through cell secretion, possessing unique advantages such as high biocompatibility, low immunogenicity, intrinsic cell targeting, and facile chemical and genetic manipulation. Importantly, miRNAs, the most prevalent non-coding RNAs, are selectively concentrated within EVs. Macrophages/microglia serve as immune defense and homeostatic cells, deriving from progenitor cells in the bone marrow. They can be classified into two contrasting types: classical proinflammatory M1 phenotype or alternative anti-inflammatory M2 phenotype. However, there exists a continuum of various intermediate phenotypes between M1 and M2, and macrophages/microglia can transition from one phenotype to another. This review will investigate recent discoveries concerning the impact of EVs derived from macrophages/microglia under various states on the progression of ischemic stroke and acute lung injury. The focus will be on the involvement of miRNAs within these vesicles. The concluding remarks of this review will underscore the clinical possibilities linked to EV-miRNAs, accentuating their potential as both biomarkers and therapeutic targets.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century. 第三阶段疫苗试验设计的过去、现在和未来:重新思考 21 世纪的统计学。
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxae104
Leila Janani, Rachel Phillips, Ellie Van Vogt, Xinxue Liu, Claire Waddington, Suzie Cro
{"title":"Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century.","authors":"Leila Janani, Rachel Phillips, Ellie Van Vogt, Xinxue Liu, Claire Waddington, Suzie Cro","doi":"10.1093/cei/uxae104","DOIUrl":"10.1093/cei/uxae104","url":null,"abstract":"<p><p>Vaccines are crucial for protecting health globally; however, their widespread use relies on rigorous clinical development programmes. This includes Phase 3 randomized controlled trials (RCTs) to confirm their safety, immunogenicity, and efficacy. Traditionally, such trials used fixed designs with predetermined assumptions, lacking the flexibility to change during the trial or stop early due to overwhelming evidence of either efficacy or futility. Modern vaccine trials benefit from innovative approaches like adaptive designs, allowing for planned trial adaptations based on accumulating data. Here, we provide an overview of the evolution of Phase 3 vaccine trial design and statistical analysis methods from traditional to more innovative contemporary methods. This includes adaptive trial designs, which offer ethical advantages and enable early termination if indicated; Bayesian methods, which combine prior knowledge and observed trial data to increase efficiency and enhance result interpretation; modern statistical analysis methods, which enable more accurate and precise inferences; the estimand framework, which ensures the primary question of interest is addressed in a trial; novel approaches using machine learning methods to assess heterogeneity of treatment effects; and statistical advances in safety analysis to evaluate reactogenicity and clinical adverse events. We conclude with insights into the future direction of vaccine trials, aiming to inform clinicians and researchers about conventional and novel RCT design and analysis approaches to facilitate the conduct of efficient, timely trials.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease. Amlexanox靶向抑制TBK1可调节免疫细胞功能,从而加剧DSS诱发的炎症性肠病。
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxae082
Lu Hui, Meng-Ke Huang, Qing-Kai Dai, Cheng-Lin Miao, Yun-Long Yang, Chen-Xi Liu, Ting Liu, Yong-Mei Jiang
{"title":"Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease.","authors":"Lu Hui, Meng-Ke Huang, Qing-Kai Dai, Cheng-Lin Miao, Yun-Long Yang, Chen-Xi Liu, Ting Liu, Yong-Mei Jiang","doi":"10.1093/cei/uxae082","DOIUrl":"10.1093/cei/uxae082","url":null,"abstract":"<p><p>Amlexanox (ALX) is a small-molecule drug for the treatment of inflammatory, autoimmune, metabolic, and tumor diseases. At present, there are no studies on whether ALX has a therapeutic effect on inflammatory bowel disease (IBD). In this study, we used a mouse model of dextran sulfate sodium-induced colitis to investigate the effect of ALX-targeted inhibition of TBK1 on colitis. We found that the severity of colitis in mice was correlated with TBK1 expression. Notably, although ALX inhibited the activation of the TBK1-NF-κB/TBK1-IRF3 pro-inflammatory signaling pathway, it exacerbated colitis and reduced survival in mice. The results of drug safety experiments ruled out a relationship between this exacerbating effect and drug toxicity. In addition, ELISA results showed that ALX promoted the secretion of IL-1β and IFN-α, and inhibited the production of cytokines IL-6, TNF-α, IL-10, TGF-β, and secretory IgA. Flow cytometry results further showed that ALX promoted T-cell proliferation, activation, and differentiation, and thus played a pro-inflammatory role; also, ALX inhibited the generation of dendritic cells and the polarization of macrophages to M1 type, thus exerting anti-inflammatory effect. These data suggest that the regulation of ALX on the function of different immune cells is different, so the effect on the inflammatory response is bidirectional. In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation of the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study. lenolisib (CDZ173)与标准护理对活化磷酸肌肽3-激酶δ (PI3Kδ)综合征(APDS)患者呼吸道感染率和血清免疫球蛋白M (IgM)水平的比较疗效:一项外部对照研究。
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxae107
John Whalen, Anita Chandra, Sven Kracker, Stephan Ehl, Markus G Seidel, Ioana Gulas, Louis Dron, Russanthy Velummailum, Chenthila Nagamuthu, Sichen Liu, Joanne Tutein Nolthenius, Maria Elena Maccari
{"title":"Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study.","authors":"John Whalen, Anita Chandra, Sven Kracker, Stephan Ehl, Markus G Seidel, Ioana Gulas, Louis Dron, Russanthy Velummailum, Chenthila Nagamuthu, Sichen Liu, Joanne Tutein Nolthenius, Maria Elena Maccari","doi":"10.1093/cei/uxae107","DOIUrl":"10.1093/cei/uxae107","url":null,"abstract":"<p><p>Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: -1.09 g/L; 95% CI: -1.78, -0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
C/EBPε and its acetylation in PMN enhance the tolerance to trauma. PMN 中的 C/EBPε 及其乙酰化可增强对创伤的耐受性。
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxae061
Shaowen Cheng, Junyu Zhu, Yangyang Bian, Jiangling Yao, Wei Zhang, Shuangqin Yin, Tianyin Kuang, Lina Xian, Huaping Liang
{"title":"C/EBPε and its acetylation in PMN enhance the tolerance to trauma.","authors":"Shaowen Cheng, Junyu Zhu, Yangyang Bian, Jiangling Yao, Wei Zhang, Shuangqin Yin, Tianyin Kuang, Lina Xian, Huaping Liang","doi":"10.1093/cei/uxae061","DOIUrl":"10.1093/cei/uxae061","url":null,"abstract":"<p><p>Severe trauma can lead to numerous serious complications, threating the well-being and vitality of the afflicted. The quantity and functionality of polymorphonuclear neutrophils (PMNs) undergo rapid transformations in response to severe trauma, playing a pivotal role in the trauma response. The absence of CCAAT/enhancer-binding protein ε (C/EBPε) profoundly impairs the functionality of PMNs, a function of paramount importance in trauma. In this study, by generating mice with C/EBPε knocked out or overexpressed, we substantiate that C/EBPε ensures the restoration of PMN function, enhancing the expression of antimicrobial proteins and thereby promoting trauma recovery. Furthermore, diminished expression of C/EBPε is observed in trauma patients, with levels displaying a negative correlation with ISS and APACHE II scores, suggesting its potential as a prognostic indicator for clinical treatment. Mechanistically, we uncover the upregulation of SIRT1 and the inhibition of P300 participating in the suppression of C/EBPε acetylation, consequently reducing the resilience of mice to trauma. Therapeutic interventions, whether through the sole administration of PMN, nicotinamide (NAM) treatment, or their combination, all result in an increased survival rate in traumatic mice. In conclusion, our study elucidates the role of C/EBPε in enhancing the resilience to trauma and identifies C/EBPε acetylation as a critical regulatory mechanism, offering potential therapeutic approaches involving PMN transfusion and NAM treatment.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency. 一项基于英国的多中心调查,研究继发于获得性C1抑制剂缺乏的血管性水肿。
IF 3.8 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxae121
Hadeil Morsi, Aarnoud Huissoon, Alexandros Grammatikos, Andrew F Whyte, Ania Manson, Anjali Ekbote, Anju Sivadasan, Anne Pacita Rosillo Boulton, Archana Herwadkar, Ariharan Anantharachagan, Arthur Price, Cathal Steele, Catherine Stroud, Charu Chopra, Dilani Arnold, Efrem Eren, Elizabeth Cleave, Elizabeth Drewe, Emily Moon, Emily Zinser, Grant Hayman, Hana Alachkar, Harichandana Ghanta, Helen Bourne, Intisar Abdelhakam, John Dempster, Katie Townsend, Kavitha Sooriyakumar, Lorena Lorenzo, Magdalena Dziadzio, Manisha Ahuja, Maria Prasinou, Marina Frleta-Gilchrist, Michael Zhang, Moira Thomas, Pavaladurai Vijayadurai, Prashantha Madhuri Vaitla, Ravishankar Sargur, Richard Herriot, Robert L Yellon, Sai Hurng Kham Murng, Sara Drinkwater, Sarah Denness, Sarah Denman, Shuayb Elkhalifa, Sinisa Savic, Sorena Kiani-Alikhan, Tania I Coulter, Tariq El-Shanawany, Tasneem Rahman, Tomaz Garcez, Patrick F K Yong, Rashmi Jain
{"title":"A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.","authors":"Hadeil Morsi, Aarnoud Huissoon, Alexandros Grammatikos, Andrew F Whyte, Ania Manson, Anjali Ekbote, Anju Sivadasan, Anne Pacita Rosillo Boulton, Archana Herwadkar, Ariharan Anantharachagan, Arthur Price, Cathal Steele, Catherine Stroud, Charu Chopra, Dilani Arnold, Efrem Eren, Elizabeth Cleave, Elizabeth Drewe, Emily Moon, Emily Zinser, Grant Hayman, Hana Alachkar, Harichandana Ghanta, Helen Bourne, Intisar Abdelhakam, John Dempster, Katie Townsend, Kavitha Sooriyakumar, Lorena Lorenzo, Magdalena Dziadzio, Manisha Ahuja, Maria Prasinou, Marina Frleta-Gilchrist, Michael Zhang, Moira Thomas, Pavaladurai Vijayadurai, Prashantha Madhuri Vaitla, Ravishankar Sargur, Richard Herriot, Robert L Yellon, Sai Hurng Kham Murng, Sara Drinkwater, Sarah Denness, Sarah Denman, Shuayb Elkhalifa, Sinisa Savic, Sorena Kiani-Alikhan, Tania I Coulter, Tariq El-Shanawany, Tasneem Rahman, Tomaz Garcez, Patrick F K Yong, Rashmi Jain","doi":"10.1093/cei/uxae121","DOIUrl":"10.1093/cei/uxae121","url":null,"abstract":"<p><strong>Background: </strong>Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterization of the AAE-C1-INH cohort in the UK is required to inform management.</p><p><strong>Objectives: </strong>To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical, and treatment profiles of AAE-associated diseases in the UK.</p><p><strong>Method: </strong>Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in the UK. Other European cohorts were compared.</p><p><strong>Results: </strong>The median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was 1 year. Antifibrinolytics and attenuated androgens showed comparable efficacy to LTP, at 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% of AAE-C1-INH patients compared to 3.4% of autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited to 23.1%. Rituximab monotherapy was effective in treating 9/9 splenic marginal zone lymphoma and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients.</p><p><strong>Conclusion: </strong>The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by the propensity to side effects. B cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deletion of thymic myoid cells regulates the thymic microenvironment involved in the progression of tumor-associated myasthenia gravis. 胸腺肌样细胞缺失调控胸腺微环境参与肿瘤相关性重症肌无力的进展
IF 3.8 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxaf043
Bo Hu, Yang Luo, Xiangyu Ding, Min Sun, Li Niu
{"title":"Deletion of thymic myoid cells regulates the thymic microenvironment involved in the progression of tumor-associated myasthenia gravis.","authors":"Bo Hu, Yang Luo, Xiangyu Ding, Min Sun, Li Niu","doi":"10.1093/cei/uxaf043","DOIUrl":"10.1093/cei/uxaf043","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is an autoimmune disease commonly associated with immune disorders in thymoma. The role of thymus myoid cells (TMCs) in the pathogenesis of autoimmune diseases has attracted much attention. Therefore, the present study was designed to reveal the impact of TMCs on the pathophysiology of tumor-associated MG (TAMG). This study included clinical patients and healthy volunteers and validated the potential role of TMCs in TAMG progression using a TMCs-deficient mouse model. Correlative findings showed that TMCs deletion affected thymic architecture in MG patients, as evidenced by the expression of key myogenic factors as well as AChR and RyRs receptors in the thymus. Further experimental validation showed that TMCs deletion increased the levels of Th1 and Th17 cells, decreased the levels of Th2 and Treg cells, and altered the secretion of corresponding cytokines, including IL-2, IL-4, IL-17, IL-22, and TGF-β concentrations. Co-culture of CD4+ T cells with Thy0517 cells or CD4+ T cells with a myoblastoid cell line using the Transwell system demonstrated that deletion of TMC inhibited the differentiation of CD4+ T cells to Treg cells. In this study, we hypothesized that TMCs are involved in TAMG progression by regulating CD4+ T cell differentiation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating T-cell-derived extracellular vesicles as biomarkers of disease activity, axonal injury, and disability in multiple sclerosis. 研究T细胞来源的细胞外囊泡作为多发性硬化症疾病活动、轴突损伤和残疾的生物标志物。
IF 3.8 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxaf003
Jennifer L Zagrodnik, Stephanie N Blandford, Neva J Fudge, Shane T Arsenault, Sarah Anthony, Lillian McGrath, Fraser Clift, Mark Stefanelli, Craig S Moore
{"title":"Investigating T-cell-derived extracellular vesicles as biomarkers of disease activity, axonal injury, and disability in multiple sclerosis.","authors":"Jennifer L Zagrodnik, Stephanie N Blandford, Neva J Fudge, Shane T Arsenault, Sarah Anthony, Lillian McGrath, Fraser Clift, Mark Stefanelli, Craig S Moore","doi":"10.1093/cei/uxaf003","DOIUrl":"10.1093/cei/uxaf003","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system, whereby clinical disease activity is primarily monitored by magnetic resonance imaging.</p><p><strong>Methods: </strong>Given the limitations associated with implementing and acquiring novel and emerging imaging biomarkers in routine clinical practice, the discovery of biofluid biomarkers may offer a more simple and cost-effective measure that would improve accessibility, standardization, and patient care. Extracellular vesicles (EVs) are nanoparticles secreted from cells under both homeostatic and pathological states, and have been recently investigated as biomarkers in MS. The objectives of this study were to longitudinally measure levels of specific immune cell-derived EVs in MS and provide evidence that EV sub-populations may serve as biomarkers of disease activity, axonal injury, and/or clinical disability.</p><p><strong>Results: </strong>Our results demonstrate that the rate of clinical disability in MS negatively correlates with changes in circulating CD3+ EVs within the plasma. Additionally, numbers of CD4+ EVs decrease in individuals with increasing pNfL levels overtime whereby the magnitude of the pNfL increase negatively correlates with changes in plasma CD4+ and CD8+ EVs. Finally, when applying NEDA-3 criteria to define active versus stable disease, individuals with active disease had significantly elevated CD4+ and CD8+ EVs compared to stable disease.</p><p><strong>Conclusion: </strong>In summary, the analysis of specific immune cell-derived EV subsets may provide a method to monitor disability accumulation, disease activity, and axonal injury in MS, while also providing insights into the pathophysiology and cellular/molecular mechanisms that influence progression.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Response to Letter to the Editor: Type 2 diabetes is associated with the accumulation of senescent T cells. 致编辑的信:2型糖尿病与衰老T细胞的积累有关。
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-21 DOI: 10.1093/cei/uxad078
Sian M Henson
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引用次数: 0
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