Frontiers in Immunology最新文献

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Corrigendum: State of play in the molecular presentation and recognition of anti-tumor lipid-based analogues.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1574591
T Praveena, Jérôme Le Nours
{"title":"Corrigendum: State of play in the molecular presentation and recognition of anti-tumor lipid-based analogues.","authors":"T Praveena, Jérôme Le Nours","doi":"10.3389/fimmu.2025.1574591","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1574591","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2024.1479382.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1574591"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Corrigendum: SARS-CoV2 infection during pregnancy causes persistent immune abnormalities in women without affecting the newborns.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1574788
Elena Vazquez-Alejo, Laura Tarancon-Diez, Itzíar Carrasco, Sara Vigil-Vázquez, Mar Muñoz-Chapuli, Elena Rincón-López, Jesús Saavedra-Lozano, Mar Santos-Sebastián, David Aguilera-Alonso, Alicia Hernanz-Lobo, Begoña Santiago-García, Juan Antonio de León-Luis, Patricia Muñoz, Manuel Sánchez-Luna, María Luisa Navarro, Mª Ángeles Muñoz-Fernández
{"title":"Corrigendum: SARS-CoV2 infection during pregnancy causes persistent immune abnormalities in women without affecting the newborns.","authors":"Elena Vazquez-Alejo, Laura Tarancon-Diez, Itzíar Carrasco, Sara Vigil-Vázquez, Mar Muñoz-Chapuli, Elena Rincón-López, Jesús Saavedra-Lozano, Mar Santos-Sebastián, David Aguilera-Alonso, Alicia Hernanz-Lobo, Begoña Santiago-García, Juan Antonio de León-Luis, Patricia Muñoz, Manuel Sánchez-Luna, María Luisa Navarro, Mª Ángeles Muñoz-Fernández","doi":"10.3389/fimmu.2025.1574788","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1574788","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2022.947549.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1574788"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Unilateral choroidal detachment in an elderly patient with Vogt-Koyanagi-Harada disease: a case report and literature review.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1514306
Chuzhi Peng, Yonghong Jiao, Chunli Chen
{"title":"Unilateral choroidal detachment in an elderly patient with Vogt-Koyanagi-Harada disease: a case report and literature review.","authors":"Chuzhi Peng, Yonghong Jiao, Chunli Chen","doi":"10.3389/fimmu.2025.1514306","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1514306","url":null,"abstract":"<p><strong>Purpose: </strong>To report an uncommon case of Vogt-Koyanagi-Harada (VKH) disease in an elderly patient with unilateral choroidal detachment and describe its multimodal imaging features and prognosis.</p><p><strong>Method: </strong>Case report and literature review of clinical features in VKH with choroidal detachment.</p><p><strong>Results: </strong>A 76-year-old woman presented with bilateral blurred vision and headache 6 months prior to visiting our hospital. She was diagnosed with iridocyclitis at another hospital and received local anti-inflammatory treatment without improvement. Slit-lamp examination showed bilateral mutton-fat and dust-like keratic precipitates, anterior chamber and vitreous cells, and posterior synechiae in the right eye. Fundus examination revealed bilateral optic disc swelling and choroidal detachment in the left eye. Fluorescein angiography revealed bilateral optic disc leakage, punctate hyperfluorescence in the posterior pole, and elevated fluorescence leakage in the left eye's temporal area. Indocyanine Green Angiography showed multiple of choroidal hypoperfusion areas in the left eye, with an elevated fluorescence blockage on the temporal side. Optical coherence tomography showed subretinal fluid, wavy retinal pigment epithelium, and choroidal thickening in both eyes. Based on ocular and neurological findings, the patient was diagnosed with bilateral VKH. After ruling out infectious factors, she received high-dose systemic corticosteroids and immunosuppressants. The choroidal detachment and serous retinal detachment gradually resolved.</p><p><strong>Conclusion: </strong>This case is the first report of unilateral choroidal detachment associated with VKH in an elderly patient. VKH patients with choroidal detachment reported in previous studies were predominantly elderly and Asian, characterized by optic disc hyperfluorescence and choroidal detachment. Multimodal imaging can help clinicians better diagnose and manage atypical types of VKH.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1514306"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Identification of immune subtypes associated with CD8+ T cell-related genes providing new treatment strategies of esophageal carcinoma.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1512230
Youyi Wu, Chen Lin, Yuchen Qian, Xiaowei Huang, Yajing Xu, Jiayi Li, Youdi He, Congying Xie, Huafang Su
{"title":"Identification of immune subtypes associated with CD8+ T cell-related genes providing new treatment strategies of esophageal carcinoma.","authors":"Youyi Wu, Chen Lin, Yuchen Qian, Xiaowei Huang, Yajing Xu, Jiayi Li, Youdi He, Congying Xie, Huafang Su","doi":"10.3389/fimmu.2025.1512230","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1512230","url":null,"abstract":"<p><strong>Background: </strong>CD8+ T lymphocytes greatly affect the efficacy of immunotherapy, displaying promising potential in various tumors. Here, we aimed to identify immune subtypes associated with CD8+ T cell-related genes to predict the efficacy of treatment in esophageal cancer (ESCA).</p><p><strong>Methods: </strong>We obtained 13 immune cell-related datasets from the Gene Expression Omnibus (GEO) database and removed batch effects. Weighted correlation network analysis (WGCNA) and co-expression analysis were performed to identify highly correlated CD8+ T cell genes. Cox analysis was used to process ESCA clinical information, and the immune clusters (ICs) were constructed through consensus cluster analysis. Furthermore, we constructed an immune risk score model to predict the prognosis of ESCA based on these CD8+ T cell genes. This model was verified using the IMvigor210 dataset, and we functionally validated the immune risk score model <i>in vitro</i>.</p><p><strong>Results: </strong>The results revealed significant correlations between CD8+ T cell-related genes and immune-related pathways. Three ICs were identified in ESCA, with IC3 demonstrating the most favorable prognosis. The final 6-gene prognostic risk model exhibited stable predictive performance in datasets across different platforms. Compared with that in normal esophageal epithelial (HEEC cells), CHMP7 in the 6-gene prognostic risk model was upregulated in KYSE150 and TE-1 cells. Si-CHMP7 transfection led to a decrease in tumor cell migration, invasion, and proliferation, accompanied by an accelerated apoptotic process.</p><p><strong>Conclusions: </strong>Collectively, we identified the immune subtypes of CD8+ T cell-related genes with different prognostic significance. We designated CHMP7 in the 6-gene prognostic risk model as a potential target to improve tumor cell prognosis. These insights provide a strong basis for improving prognosis and facilitating more personalized and accurate treatment decisions for the immunotherapy of ESCA.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1512230"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Identify the potential target of efferocytosis in knee osteoarthritis synovial tissue: a bioinformatics and machine learning-based study.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1550794
Shangbo Niu, Mengmeng Li, Jinling Wang, Peirui Zhong, Xing Wen, Fujin Huang, Linwei Yin, Yang Liao, Jun Zhou
{"title":"Identify the potential target of efferocytosis in knee osteoarthritis synovial tissue: a bioinformatics and machine learning-based study.","authors":"Shangbo Niu, Mengmeng Li, Jinling Wang, Peirui Zhong, Xing Wen, Fujin Huang, Linwei Yin, Yang Liao, Jun Zhou","doi":"10.3389/fimmu.2025.1550794","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1550794","url":null,"abstract":"<p><strong>Introduction: </strong>Knee osteoarthritis (KOA) is a degenerative joint disease characterized by the progressive deterioration of cartilage and synovial inflammation. A critical mechanism in the pathogenesis of KOA is impaired efferocytosis in synovial tissue. The present study aimed to identify and validate key efferocytosis-related genes (EFRGs) in KOA synovial tissue by using comprehensive bioinformatics and machine learning approaches.</p><p><strong>Methods: </strong>We integrated three datasets (GSE55235, GSE55457, and GSE12021) from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) associated with efferocytosis and performed weighted gene co-expression network analysis. Subsequently, we utilized univariate logistic regression analysis, least absolute shrinkage and selection operator regression, support vector machine, and random forest algorithms to further refine these genes. The results were then inputted into multivariate logistic regression analysis to construct a diagnostic nomogram. Public datasets and quantitative real-time PCR experiments were employed for validation. Additionally, immune infiltration analysis was conducted with CIBERSORT using the combined datasets.</p><p><strong>Results: </strong>Analysis of the intersection between DEGs and EFRGs identified 12 KOA-related efferocytosis DEGs. Further refinement through machine learning algorithms and multivariate logistic regression revealed UCP2, CX3CR1, and CEBPB as hub genes. Immune infiltration analysis demonstrated significant correlations between immune cell components and the expression levels of these hub genes. Validation using independent datasets and experimental approaches confirmed the robustness of these findings.</p><p><strong>Conclusions: </strong>This study successfully identified three hub genes (UCP2, CX3CR1, and CEBPB) with significant expression alterations in KOA, demonstrating high diagnostic potential and close associations with impaired efferocytosis. These targets may modulate synovial efferocytosis-related immune processes, offering novel therapeutic avenues for KOA intervention.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1550794"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The gut-brain-axis one year after treatment with cladribine tablets in patients with relapsing remitting multiple sclerosis: a pilot study.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1514762
Jeske van Pamelen, Carla Rodriguez-Mogeda, Lynn van Olst, Susanne M A van der Pol, Maarten L Boon, Janet de Beukelaar, Oliver H H Gerlach, Andries E Budding, Joep Killestein, Helga E de Vries, Leo H Visser
{"title":"The gut-brain-axis one year after treatment with cladribine tablets in patients with relapsing remitting multiple sclerosis: a pilot study.","authors":"Jeske van Pamelen, Carla Rodriguez-Mogeda, Lynn van Olst, Susanne M A van der Pol, Maarten L Boon, Janet de Beukelaar, Oliver H H Gerlach, Andries E Budding, Joep Killestein, Helga E de Vries, Leo H Visser","doi":"10.3389/fimmu.2025.1514762","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1514762","url":null,"abstract":"<p><strong>Introduction: </strong>Cladribine tablets are an effective treatment for relapsing remitting multiple sclerosis (RRMS). However, almost half of the treated patients are not free of disease activity after two years. The aim of this study was to describe the changes that cladribine tablets effectuate in the gut and oral microbiota and the peripheral immunological profile between responders and non-responders.</p><p><strong>Methods: </strong>In this pilot study of the multicenter, prospective, observational BIA (Brain-Immune-Intestine Axis) study, we included patients aged 18 to 55 years with RRMS who were scheduled to start treatment with cladribine tablets. We assessed the clinical status and the immunological and microbiological profile prior to the start of the treatment and after three and twelve months. At twelve months, we assessed the response status, based on clinical relapses, radiological activity and disability progression on the Expanded Disability Status Scale.</p><p><strong>Results: </strong>The first twenty-five patients of the BIA study were included in this analysis. Ten patients (40%) were responders twelve months after treatment. Three months after treatment we found a significant decline of naïve and transitional B cells and memory B cells, and of CD57<sup>+</sup> CD56<sup>dim</sup> NK cells. After twelve months the values recovered to baseline levels, except for the memory B cells. We did not find significant changes of the microbiological profile over time, except for a decline of the phylum <i>Bacteroidetes</i> in the oral samples twelve months after treatment. Baseline values and changes over time did not significantly differ between responders and non-responders. However, several phyla, genera or species (<i>Bacteroidetes, Prevotella, Faecalibacterium prausnitzii)</i> showed a higher relative abundance, and several phyla, genera or species (<i>Proteobacteria, Escherichia coli)</i> had a lower relative abundance in responders compared to non-responders.</p><p><strong>Discussion: </strong>After treatment with cladribine tablets, we found significant changes in the immunological landscape. Also, the microbiological profile showed several differences in microbes with known anti- or pro-inflammatory properties between responders and non-responders. Overall, we showed that we can measure a treatment effect from cladribine tablets with our analyses. Future research on data from the BIA study, with a larger sample size and extended follow-up, can possibly confirm the reliability of our findings.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1514762"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Growth arrest and DNA damage-inducible 45: a new player on inflammatory diseases.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1513069
Yanmei Ma, Md Munnaf Hossen, Jennifer Jin Huang, Zhihua Yin, Jing Du, Zhizhong Ye, Miaoyu Zeng, Zhong Huang
{"title":"Growth arrest and DNA damage-inducible 45: a new player on inflammatory diseases.","authors":"Yanmei Ma, Md Munnaf Hossen, Jennifer Jin Huang, Zhihua Yin, Jing Du, Zhizhong Ye, Miaoyu Zeng, Zhong Huang","doi":"10.3389/fimmu.2025.1513069","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1513069","url":null,"abstract":"<p><p>Growth arrest and DNA damage-inducible 45 (GADD45) proteins are critical stress sensors rapidly induced in response to genotoxic/physiological stress and regulate many cellular functions. Even though the primary function of the proteins is to block the cell cycle, inhibit cell proliferation, promote cell apoptosis, and repair DNA damage to cope with the damage caused by internal and external stress on the body, evidence has shown that GADD45 also has the function to modulate innate and adaptive immunity and plays a broader role in inflammatory and autoimmune diseases. In this review, we focus on the immunomodulatory role of GADD45 in inflammatory and autoimmune diseases. First, we describe the regulatory factors that affect the expression of GADD45. Then, we introduce its immunoregulatory roles on immune cells and the critical signaling pathways mediated by GADD45. Finally, we discuss its immunomodulatory effects in various inflammatory and autoimmune diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1513069"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The various roles of TREM2 in cardiovascular disease.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1462508
Shuai Wang, Chenghui Cao, Daoquan Peng
{"title":"The various roles of TREM2 in cardiovascular disease.","authors":"Shuai Wang, Chenghui Cao, Daoquan Peng","doi":"10.3389/fimmu.2025.1462508","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1462508","url":null,"abstract":"<p><p>Triggering receptor expressed on myeloid cells-2 (TREM2) is a transmembrane immune receptor that is expressed mainly on macrophages. As a pathology-induced immune signaling hub, TREM2 senses tissue damage and activates immune remodeling in response. Previous studies have predominantly focused on the TREM2 signaling pathway in Alzheimer's disease, metabolic syndrome, and cancer. Recent research has indicated that TREM2 signaling is also activated in various cardiovascular diseases. In this review, we summarize the current understanding and the unanswered questions regarding the role of TREM2 signaling in mediating the metabolism and function of macrophages in atherosclerosis and various models of heart failure. In the context of atherosclerosis, TREM2 signaling promotes foam cell formation and is crucial for maintaining macrophage survival and plaque stability through efferocytosis and cholesterol efflux. Recent studies on myocardial infarction, sepsis-induced cardiomyopathy, and hypertensive heart failure also implicated the protective role of TREM2 signaling in cardiac macrophages through efferocytosis and paracrine functions. Additionally, we discuss the clinical significance of elevated soluble TREM2 (sTREM2) in cardiovascular disease and propose potential therapies targeting TREM2. The overall aim of this review is to highlight the various roles of TREM2 in cardiovascular diseases and to provide a framework for therapeutic strategies targeting TREM2.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1462508"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1520619
Paolo Durigutto, Maria Cristina Grimaldi, Sara Bozzer, Elena Raschi, Pierluigi Meroni, Francesco Tedesco, Paolo Macor
{"title":"β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model.","authors":"Paolo Durigutto, Maria Cristina Grimaldi, Sara Bozzer, Elena Raschi, Pierluigi Meroni, Francesco Tedesco, Paolo Macor","doi":"10.3389/fimmu.2025.1520619","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1520619","url":null,"abstract":"<p><p>Anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic vascular occlusion and maternal morbidity. Anti-coagulants remain pivotal drugs for the management of APS, but a significant proportion of patients do not benefit from long-term anti-coagulation and may require an alternative therapy to prevent antibody deposition and vascular thrombosis. We have developed a therapeutic approach based on the use of safe polymeric nanoparticles that selectively target beta2-glycoprotein I (β2GPI) deposited on endothelial cells (tNPs). Their efficacy was tested in a rat model of APS developed by infusing patients' sera containing medium-high titer antibodies against domain I of β2GPI. The tNPs bearing a CH2-deleted anti-β2GPI recombinant antibody as a targeting agent recognize β2GPI deposited on endothelial cells but failed to induce blood clot formation. The tNPs infused into rats immediately before APS sera competed with patients' antibodies, preventing their binding to deposited β2GPI and, as a consequence, resulted in thrombus formations and occlusion of mesenteric vessels. Similar results were obtained by injecting tNPs 24 hours before the administration of patients' sera to induce blood clot formation. Our findings suggest that β2GPI-targeted polymeric nanoparticles represent a stable and safe approach to prevent thrombus formation and vessel occlusion in a rat model of APS and may be used to control thrombosis developing in APS patients as a result of acute triggering events.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1520619"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Gut microbiota is associated with persistence of longer-term BNT162b2 vaccine immunogenicity.
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2025-02-27 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1534787
Ho Yu Ng, Yunshi Liao, Ching Lung Cheung, Ruiqi Zhang, Kwok Hung Chan, Wai-Kay Seto, Wai K Leung, Ivan F N Hung, Tommy T Y Lam, Ka Shing Cheung
{"title":"Gut microbiota is associated with persistence of longer-term BNT162b2 vaccine immunogenicity.","authors":"Ho Yu Ng, Yunshi Liao, Ching Lung Cheung, Ruiqi Zhang, Kwok Hung Chan, Wai-Kay Seto, Wai K Leung, Ivan F N Hung, Tommy T Y Lam, Ka Shing Cheung","doi":"10.3389/fimmu.2025.1534787","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1534787","url":null,"abstract":"<p><strong>Introduction: </strong>BNT162b2 immunogenicity wanes with time and we investigated association between gut microbiota and longer-term immunogenicity.</p><p><strong>Methods: </strong>This cohort study prospectively recruited adult BNT162b2 two-dose recipients from three vaccination centers in Hong Kong. Blood samples were collected at baseline and day 180 after first dose, and tested for neutralizing antibodies (NAb) against receptor-binding domain (RBD) of wild type SARS-CoV-2 virus using chemiluminescence immunoassay. Shotgun DNA metagenomic sequencing was performed to characterize baseline stool microbiome. Baseline metabolites were measured by gas and liquid chromatography-tandem mass spectrometry (GC-MS/MS and LC-MS/MS). Primary outcome was persistent high NAb response (defined as top 25% of NAb level) at day 180. Putative bacterial species and metabolic pathways were identified using linear discriminant analysis [LDA] effect size analysis. Multivariable logistic regression adjusting for clinical factors was used to derive adjusted odds ratio (aOR) of outcome with bacterial species and metabolites.</p><p><strong>Results: </strong>Of 242 subjects (median age: 50.2 years [IQR:42.5-55.6]; male:85 [35.1%]), 61 (25.2%) were high-responders while 33 (13.6%) were extreme-high responders (defined as NAb≥200AU/mL). None had COVID-19 at end of study. <i>Ruminococcus bicirculans</i> (log<sub>10</sub>LDA score=3.65), <i>Parasutterella excrementihominis</i> (score=2.82) and <i>Streptococcus salivarius</i> (score=2.31) were enriched in high-responders, while <i>Bacteroides thetaiotaomicron</i> was enriched in low-responders (score=-3.70). On multivariable analysis, bacterial species (<i>R. bicirculans</i>-aOR: 1.87, 95% CI: 1.02-3.51; <i>P. excrementihominis</i>-aOR: 2.2, 95% CI: 1.18-4.18; S. <i>salivarius</i>-aOR: 2.09, 95% CI: 1.13-3.94) but not clinical factors associated with high response. <i>R. bicirculans</i> positively correlated with most metabolic pathways enriched in high-responders, including superpathway of L-cysteine biosynthesis (score=2.25) and L-isoleucine biosynthesis I pathway (score=2.16) known to benefit immune system. Baseline serum butyrate (aOR:10.00, 95% CI:1.81-107.2) and isoleucine (aOR:1.17, 95% CI:1.04-1.35) significantly associated with extreme-high vaccine response.</p><p><strong>Conclusion: </strong>Certain gut bacterial species, metabolic pathways and metabolites associate with longer-term COVID-19 vaccine immunogenicity.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1534787"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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