Frontiers in Immunology最新文献

{"title":"<i>Clonorchis sinensis-</i>infected hepatocellular carcinoma exhibits distinct tumor microenvironment and molecular features.","authors":"Junxian Chen, Caibiao Wei, Wencheng Huang, Taijun Huang, Lingling Zhou, Yulong Xu, Yuling Qin, Qiumei Lin, Fengfei Liu, Xiaolan Pan, Zeli Tang, Weilong Yang, Min Fang","doi":"10.3389/fimmu.2025.1526699","DOIUrl":"10.3389/fimmu.2025.1526699","url":null,"abstract":"<p><strong>Objectives: </strong><i>Clonorchis sinensis</i> (<i>Cs</i>)-infected hepatocellular carcinoma (HCC) patients have a poorer prognosis than non-<i>Cs</i>-infected HCCs. However, the molecular mechanisms of <i>Cs</i>-infected HCC remain unclear. To address this, this study aims to uncover the tumor microenvironment and molecular features that may contribute to these poor outcomes.</p><p><strong>Methods: </strong>The research involved bulk RNA sequencing of paired tumor and adjacent tissue samples from 10 <i>Cs</i> ⁺ HCC and 10 <i>Cs</i> ^- HCC patients. Differentially expressed genes were identified, followed by enrichment analyses to reveal functional changes. Survival analysis of the top 10 up- and down-regulated genes in <i>Cs</i> ⁺ HCC tumors was performed using TCGA database. Additionally, clinical data from 1,461 HCC patients were retrospectively analyzed to assess the impact of <i>Cs</i> infection on microvascular invasion and metastasis rates. <i>In vitro</i> assays were also conducted using <i>Cs</i> excretory/secretory products (<i>Cs</i>ESPs) to examine their effect on HCC cells and HUVECs.</p><p><strong>Results: </strong>We identified 785 up-regulated and 675 down-regulated genes in <i>Cs</i> ⁺ HCC tumors compared to <i>Cs</i> ^- HCC tumors, enriched in pathways related to extracellular matrix remodeling and immunosuppression. Survival analysis revealed that the top 10 up-regulated genes are associated with HCC poor prognosis. Clinical data from 1,461 HCC patients showed <i>Cs</i> infection increased microvascular invasion and metastasis rates. <i>In vitro</i>, <i>Cs</i>ESPs products enhanced migration and invasion in HCC cells and promoted tube formation in human umbilical vein endothelial cells.</p><p><strong>Conclusions: </strong>This study provides novel insights into the molecular landscape of <i>Cs</i>-infected HCC and underscores the <i>Cs</i> infection's role in enhancing tumor migration, invasion and angiogenesis. The findings contribute to the understanding of parasitic infections in cancer progression and suggest potential prognostic markers for <i>Cs</i> ⁺ HCC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1526699"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752103","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}

{"title":"<i>In silico</i> evidence of monkeypox F14 as a ligand for the human TLR1/2 dimer.","authors":"Ankita Chakraborty, Nabarun Chandra Das, Parth Sarthi Sen Gupta, Saroj Kumar Panda, Malay Kumar Rana, Srinivasa Reddy Bonam, Jagadeesh Bayry, Suprabhat Mukherjee","doi":"10.3389/fimmu.2025.1544443","DOIUrl":"10.3389/fimmu.2025.1544443","url":null,"abstract":"<p><p>Recent emergence of zoonotic monkeypox virus (Mpox) in human has triggered the virologists to develop plausible preventive measures. Hitherto, our understanding on the mechanism of immunopathogenesis of Mpox infection is elusive. However, available experimental evidences suggest induction of inflammation as the main cause of pathogenesis. Toll-like receptors (TLRs) are critical in initiating and modulating the host immune response to pathogens. Inflammatory responses observed in various poxvirus infections have, in fact, been shown to be mediated through TLR activation. Therefore, by in silico approaches, this study seeks to identify the Mpox antigen(s) (MAg) that are most likely to interact with human cell-surface TLRs. The Mpox proteomics data available in UniProt database contain 174 protein sequences, among which 105 immunoreactive proteins were modeled for 3D structure and examined for comparative protein-protein interactions with the TLRs through molecular docking and molecular dynamics simulation. F14, an 8.28 kDa infective protein of Mpox, was found to exhibit strong binding affinity (ΔG=-12.5 Kcal mol^-1) to TLR1/2 dimer to form a compact thermodynamically stable protein complex. Interestingly, a significant level of conformational change was also observed in both F14 and TLR6 while forming F14-TLR1/2 complex. Based on these data we propose F14 as a putative ligand of human TLR1/2 to initiate proinflammatory signaling in the Mpox-infected host.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1544443"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752107","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}

{"title":"Healthy and premature aging of monocytes and macrophages.","authors":"Syamantak Basu, Ying Ulbricht, Manuela Rossol","doi":"10.3389/fimmu.2025.1506165","DOIUrl":"10.3389/fimmu.2025.1506165","url":null,"abstract":"<p><p>Aging is associated with immunosenescence, a decline in immune functions, but also with inflammaging, a chronic, low-grade inflammation, contributing to immunosenescence. Monocytes and macrophages belong to the innate immune system and aging has a profound impact on these cells, leading to functional changes and most importantly, to the secretion of pro-inflammatory cytokines and thereby contributing to inflammaging. Rheumatoid arthritis (RA) is an autoimmune disease and age is an important risk factor for developing RA. RA is associated with the early development of age-related co-morbidities like cardiovascular manifestations and osteoporosis. The immune system of RA patients shows signs of premature aging like age-inappropriate increased production of myeloid cells, accelerated telomeric erosion, and the uncontrolled production of pro-inflammatory cytokines. In this review we discuss the influence of aging on monocytes and macrophages during healthy aging and premature aging in rheumatoid arthritis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1506165"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752040","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}

{"title":"High tumor CD161 expression predicts a survival advantage and marks a Th1-skewed microenvironment.","authors":"Briana Amicarella Burns, Manasvi Chandra, Vanaja Konduri, William K Decker","doi":"10.3389/fimmu.2025.1522755","DOIUrl":"10.3389/fimmu.2025.1522755","url":null,"abstract":"<p><p>CD8⁺CD161⁺ T-cells exhibit augmented memory and cytolytic properties, mediating enhanced immunity in murine tumor models and improved survival in human non-small cell lung cancer. This T-cell subset might serve as a biomarker of positive response to therapy or even be isolated to augment current immunotherapeutic approaches yet limited knowledge of CD161 expression in human cancers restricts practical application. Here we bioinformatically tested the hypothesis that CD161 expression may be associated with positive outcomes in human cancers and investigated mechanisms underlying any observed advantages. Using TCGA-PANCAN dataset, we analyzed expression of CD161 in over 10,000 human tumors, correlating expression levels with survival. CD161 expression was highly correlated and largely co-expressed with CD8, indicating that observed benefits could be attributed to CD8⁺CD161⁺ T-cells. While patients with high CD161 expression exhibited a clear survival advantage over those with low expression, this survival advantage was highly dependent on co-expression of CD11c, indicating a reliance on dendritic cells (DC). To further explore the mechanism by which high CD161 expression confers a survival advantage in cancer, we analyzed available scRNA-sequencing data derived from 31 melanoma tumors. Tumors exhibiting high CD8⁺CD161⁺ infiltration also exhibited greater expression of cDC1 and T_H1 transcription factors along with higher levels of inflammatory cytokine transcripts. CD8⁺CD161⁺ cells themselves displayed enhanced cytotoxicity markers and reduced exhaustion markers compared to CD8⁺CD161^neg T-cells. The data suggest that CD161 could serve as a biomarker for positive outcomes and that DC play a critical <i>in vivo</i> role in the propagation of CD161⁺ T-cell responses.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1522755"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752151","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}

{"title":"The relationship between vitamin D levels, D-dimer and platelet parameter levels in patients with gestational hypertension.","authors":"Pingping Wang, Jin Yao, Yaqiong Li, Zhanjun Zhang, Ruiling Zhang, Shouting Lu, Meixia Sun, Xiaorong Huang","doi":"10.3389/fimmu.2025.1509719","DOIUrl":"10.3389/fimmu.2025.1509719","url":null,"abstract":"<p><strong>Introduction: </strong>Hypertension during pregnancy is a common pregnancy complication that has an important impact on maternal and fetal health. In recent years, studies have shown that vitamin D, D dimers and platelet parameters may play a key role in the occurrence and development of gestational hypertension.</p><p><strong>Objective: </strong>This study aimed to explore the relationship between vitamin D levels, D dimers and platelet parameters in patients with gestational hypertension.</p><p><strong>Material and methods: </strong>This study retrospectively analyzed the clinical data of 90 patients with gestational hypertension and 90 normal pregnant women who were treated in our hospital from September 2022 to September 2023. We compared the blood routine indicators between the two groups, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), etc., as well as D dimer and vitamin D (Vit D) levels.</p><p><strong>Results: </strong>The results showed that the vitamin D level and PLT in the gestational hypertension group were significantly lower than those in the normal pregnant group, while MPV and PDW were significantly increased. In addition, vitamin D levels were significantly correlated with D dimer, MPV and PDW. Further statistical analysis showed that vitamin D, D dimer and platelet parameters were important predictors of gestational hypertension.</p><p><strong>Conclusion: </strong>This study found that patients with gestational hypertension have vitamin D deficiency and abnormal platelet function. Vitamin D may affect the development of the disease by regulating platelet activity and coagulation status, which may be closely related to its pathological mechanism. This suggests that improving vitamin D status may have potential value in the management of gestational hypertension.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1509719"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752156","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}

{"title":"Sodium citrate pretreatment enhances CAR-T cell persistence and anti-tumor efficacy through inhibition of calcium signaling.","authors":"Xuechen Yin, Wenwen Chen, Xudong Ao, Luxia Xu, Jiujiu Cao, Tinghui Huang, Junqing Liang, Jianhua Hu, Jiaqi Liu, Xinping Wang, Wenying Li, Muya Zhou, Lingfeng He, Zhigang Guo","doi":"10.3389/fimmu.2025.1540754","DOIUrl":"10.3389/fimmu.2025.1540754","url":null,"abstract":"<p><strong>Introduction: </strong>Chimeric antigen receptor T cell (CAR-T) therapy has shown success in treating hematological malignancies, but its effectiveness against solid tumors is hindered by T cell exhaustion. During <i>in vitro</i> expansion, tonic signaling induced by CAR expression contributes to CAR-T cell exhaustion, which can be mitigated by inhibiting calcium signaling. Given that sodium citrate can chelate calcium ions and inhibit calcium signaling, in this study, we investigated whether sodium citrate could reduce exhaustion and enhance CAR-T cell function.</p><p><strong>Methods: </strong>We constructed anti-CD70 CAR-T cells and cultured them in the presence of sodium citrate. The characteristics and functionality of sodium citrate-pretreated CAR-T cells were assessed through <i>in vitro</i> and <i>in vivo</i> experiments. To further validate our observation, we also treated anti-mesothelin (MSLN) CAR-T cells with sodium citrate and detected the phenotypes and anti-tumor function of CAR-T cells.</p><p><strong>Results: </strong>We found that sodium citrate-pretreated anti-CD70 CAR-T cells exhibited reduced exhaustion, increased memory T cell proportions, and enhanced anti-tumor efficacy both <i>in vitro</i> and <i>in vivo</i>. Notably, sodium citrate treatment improved the <i>in vivo</i> persistence of CAR-T cells and prevented tumor recurrence. These beneficial effects were also observed in anti-MSLN CAR-T cells. Transcriptomic and metabolite analyses revealed that sodium citrate inhibited calcium signaling, mTORC1 activity, and glycolysis pathways, thus modulating T cell exhaustion and differentiation.</p><p><strong>Discussion: </strong>Our findings suggest that sodium citrate supplementation during CAR-T cell expansion could be a promising strategy to improve CAR-T therapy for solid tumors by preventing exhaustion and promoting memory T cell formation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1540754"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752122","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}

{"title":"Nanoparticle platform preferentially targeting liver sinusoidal endothelial cells induces tolerance in CD4+ T cell-mediated disease models.","authors":"Shu-Hung Wang, Isabelle Serr, Reinaldo Digigow, Barbara Metzler, Alexey Surnov, Cornelia Gottwick, Muhammad Alsamman, Daria Krzikalla, Markus Heine, Miriam Zahlten, Agata Widera, Disha Mungalpara, Muharrem Şeleci, Marco Fanzutti, Lígia Margarida Marques Mesquita, Anna-Lisa Vocaturo, Johannes Herkel, Antonella Carambia, Christian Schröter, Dikran Sarko, Johannes Pohlner, Carolin Daniel, Cristina de Min, Sabine Fleischer","doi":"10.3389/fimmu.2025.1542380","DOIUrl":"10.3389/fimmu.2025.1542380","url":null,"abstract":"<p><strong>Introduction: </strong>Treating autoimmune diseases without nonspecific immunosuppression remains challenging. To prevent or treat these conditions through targeted immunotherapy, we developed a clinical-stage nanoparticle platform that leverages the tolerogenic capacity of liver sinusoidal endothelial cells (LSECs) to restore antigen-specific immune tolerance.</p><p><strong>Methods: </strong><i>In vivo</i> efficacy was evaluated in various CD4⁺ T cell-mediated disease models, including preventive and therapeutic models of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), ovalbumin-sensitized delayed-type hypersensitivity (DTH), and the spontaneous type 1 diabetes model. Nanoparticle-induced antigen-specific immune responses were also analyzed through adoptive transfers of 2D2 transgenic T cells into wild-type mice, followed by nanoparticle administration.</p><p><strong>Results: </strong>The peptide-conjugated nanoparticles displayed a uniform size distribution (25-30 nm). Their coupling efficiency for peptides with unfavorable physicochemical properties was significantly enhanced by a proprietary linker technology. Preferential LSEC targeting of nanoparticles coupled with fluorescently labeled peptides was confirmed via intravital microscopy and flow cytometry. Intravenous nanoparticle administration significantly reduced disease severity and demyelination in EAE, independent of prednisone at maintenance doses, and suppressed target tissue inflammation in the DTH model. Furthermore, prophylactic administration of a mixture of nanoparticles coupled with five autoantigenic peptides significantly lowered the hyperglycemia incidence of the non-obese diabetic mice. Mechanistically, the tolerizing effects were associated with the induction of antigen-specific regulatory T cells and T cell anergy, which counteract proinflammatory T cells in the target tissue.</p><p><strong>Conclusion: </strong>Our findings demonstrate that peptide-loaded nanoparticles preferentially deliver disease-relevant peptides to LSECs, thereby inducing antigen-specific immune tolerance. This versatile clinical-stage nanoparticle platform holds promise for clinical application across multiple autoimmune diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1542380"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751705","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}

{"title":"Non-neutralizing anti-type I interferon autoantibodies could increase thrombotic risk in critical COVID-19 patients.","authors":"Mario Framil, Lydia García-Serrano, Francisco Morandeira, Juan Francisco Luchoro, Arnau Antolí, Jose Luis Gomez-Vazquez, Àngels Sierra-Fortuny, Xavier Solanich","doi":"10.3389/fimmu.2025.1556731","DOIUrl":"10.3389/fimmu.2025.1556731","url":null,"abstract":"<p><p>During the COVID-19 pandemic, approximately 15% of patients with severe COVID-19 pneumonia were reported to have neutralizing anti-type I interferon (IFN) autoantibodies, which impaired the antiviral response and led to a poorer prognosis. However, the physiological impact of non-neutralizing autoantibodies remains unclear. In our cohort of COVID-19 patients admitted to intensive care, the presence of non-neutralizing anti-type I IFN autoantibodies increased the risk of thrombotic complications, likely via a cytokine carrier mechanism, prolonging the half-life of cytokines and dysregulating vascular endothelial function. Previous studies have associated non-neutralizing anti-type I IFN autoantibodies with an increased risk of cardiovascular complications in autoimmune diseases like systemic lupus erythematosus, but their relevance in infectious diseases remains uncertain. Stratifying anti-type I IFN autoantibodies based on their neutralizing capacity may have clinical significance not only in terms of susceptibility to infectious diseases but also in predicting cardiovascular and thrombotic events.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1556731"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752069","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}

{"title":"The communication role of extracellular vesicles in the osteoarthritis microenvironment.","authors":"Pu Chen, Lingfeng Zeng, Ting Wang, Jianbo He, Shuai Xiong, Gang Chen, Qingfu Wang, Haiyun Chen, Jiewei Xie","doi":"10.3389/fimmu.2025.1549833","DOIUrl":"10.3389/fimmu.2025.1549833","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common degenerative joint disease worldwide, characterized by synovial inflammation, cartilage loss, and reactive hyperplasia of subchondral bone, affecting the quality of life of hundreds of millions of people. However, the molecular mechanisms underlying the occurrence and progression of OA remain unclear, and there is no therapy can substantially interrupt or reverse the destructive process of OA. More insight into the pathogenesis of OA may result in innovative therapeutics. The OA microenvironment plays a pivotal role in the development and progression of OA, which encompasses chondrocytes, adipocytes, synovial fibroblasts, endothelial cells, and immune cells. Extracellular vesicles (EVs) have emerged as a novel form of intercellular communication, mediating the transfer of a range of bioactive molecules to create a specific microenvironment. Recent studies have reported that the cargos of EVs play a crucial role in the pathogenesis of OA, including noncoding RNAs (ncRNAs), proteins, and lipids. This review systematically analyzes and summarizes the biological characteristics and functionalities of EVs derived from diverse cellular sources, especially how EVs mediate communication between different cells in the OA microenvironment, with a view to providing new insights into the pathogenesis of OA.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1549833"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752152","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}

{"title":"Immunoglobulin G <i>N</i>-Glycome as a biomarker of mortality risk in <i>Escherichia coli</i> induced sepsis.","authors":"Huachen Wang, Houqiang Li, Zheng Guo, Hongda Hou, Haifeng Hou, Bing Chen","doi":"10.3389/fimmu.2025.1532145","DOIUrl":"10.3389/fimmu.2025.1532145","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening syndrome caused by an imbalance in the inflammatory response to an infection that can lead to a high mortality rate. <i>Escherichia coli</i> is a common pathogen that causes sepsis. The role of immunoglobulin G <i>N</i>-glycome in estimating the mortality in patients with sepsis remains unknown. This study aims to reveal the clinical application of immunoglobulin G <i>N</i>-glycome as a potentially novel biomarker to predict mortality risk in <i>Escherichia coli</i>-induced sepsis.</p><p><strong>Methods: </strong>The serum immunoglobulin G <i>N</i>-glycome levels in 100 adult septic patient serum samples on the day of intensive care unit (ICU) admission, and 100 healthy volunteers were measured and analyzed. Immunoglobulin G <i>N</i>-glycome was compared with existing risk scores on predicting in-hospital death.</p><p><strong>Results: </strong>We identified that the fucosylation level was significantly decreased in patients. Importantly, bisecting GlcNAc, sialylation, and galactosylation have different levels between sepsis and control groups. In addition, the AUC values of the SOFA score combined with GP4, GP5, and GP9 were 0.76 (95%CI: 0.61 to 0.90), 0.58 (95%CI: 0.40 to 0.7) and 0.57 (95%CI: 0.38 to 0.76). The AUC value of the SOFA score combined with GP4 and GP7 was 0.85 (95%CI: 0.76 to 0.93) in predicting in-hospital mortality in patients with sepsis.</p><p><strong>Conclusions: </strong>Immunoglobulin G <i>N</i>-glycome concentrations at ICU admission are valuable for predicting the in-hospital mortality risk of patients with sepsis, suggesting that immunoglobulin G <i>N</i>-glycome may be a novel biomarker.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1532145"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752153","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}