{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:29:05Z","timestamp":1792459745062,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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. <jats:italic>Escherichia coli<\/jats:italic> is a common pathogen that causes sepsis. The role of immunoglobulin G <jats:italic>N<\/jats:italic>-glycome in estimating the mortality in patients with sepsis remains unknown. This study aims to reveal the clinical application of immunoglobulin G <jats:italic>N<\/jats:italic>-glycome as a potentially novel biomarker to predict mortality risk in <jats:italic>Escherichia coli<\/jats:italic>-induced sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The serum immunoglobulin G <jats:italic>N<\/jats:italic>-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 <jats:italic>N<\/jats:italic>-glycome was compared with existing risk scores on predicting in-hospital death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Immunoglobulin G <jats:italic>N<\/jats:italic>-glycome concentrations at ICU admission are valuable for predicting the in-hospital mortality risk of patients with sepsis, suggesting that immunoglobulin G <jats:italic>N<\/jats:italic>-glycome may be a novel biomarker.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1532145","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:18:10Z","timestamp":1742195890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunoglobulin G N-Glycome as a biomarker of mortality risk in Escherichia coli induced sepsis"],"prefix":"10.3389","volume":"16","author":[{"given":"Huachen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongda","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/S1473-3099(15)70112-X","article-title":"Sepsis: a roadmap for future research","volume":"15","author":"Cohen","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1039\/D3TB02220J","article-title":"Recent advances and prospects in nanomaterials for bacterial sepsis management","volume":"11","author":"Zhou","year":"2023","journal-title":"J Mater Chem B"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.2c02560","article-title":"Macrophage-Membrane-Camouflaged nonviral gene vectors for the treatment of multidrug-resistant bacterial sepsis","volume":"22","author":"Cao","year":"2022","journal-title":"Nano Lett"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0781OC","article-title":"Assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations","volume":"193","author":"Fleischmann","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30080-1","article-title":"Immunomodulation by macrolides: therapeutic potential for critical care","volume":"8","author":"Reijnders","year":"2020","journal-title":"Lancet Respir Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41590-023-01660-5","article-title":"The pathophysiology of sepsis and precision-medicine-based immunotherapy","volume":"25","author":"Giamarellos-Bourboulis","year":"2024","journal-title":"Nat Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1953220","DOI":"10.1080\/19420862.2021.1953220","article-title":"The therapeutic potential of sialylated Fc domains of human IgG","volume":"13","author":"Pleass","year":"2021","journal-title":"MAbs"},{"key":"B8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.chom.2020.12.017","article-title":"Loss of \u03b1-gal during primate evolution enhanced antibody-effector function and resistance to bacterial sepsis","volume":"29","author":"Singh","year":"2021","journal-title":"Cell Host Microbe"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011616","article-title":"DENV-specific IgA contributes protective and non-pathologic function during antibody-dependent enhancement of DENV infection","volume":"19","author":"Wegman","year":"2023","journal-title":"PloS Pathog"},{"key":"B10","doi-asserted-by":"publisher","first-page":"104101","DOI":"10.1016\/j.ebiom.2022.104101","article-title":"IgG N-glycome changes during the course of severe COVID-19: An observational study","volume":"81","author":"Petrovi\u0107","year":"2022","journal-title":"EBioMedicine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188838","article-title":"The role of N-glycosylation in B-cell biology and IgG activity. The aspects of autoimmunity and anti-inflammatory therapy","volume":"14","author":"Trzos","year":"2023","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1053\/j.gastro.2019.08.060","article-title":"Protein glycosylation as a diagnostic and prognostic marker of chronic inflammatory gastrointestinal and liver diseases","volume":"158","author":"Verhelst","year":"2020","journal-title":"Gastroenterology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.jaci.2019.10.012","article-title":"IgG Fc glycosylation as an axis of humoral immunity in childhood","volume":"145","author":"Cheng","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1146\/annurev.immunol.25.022106.141702","article-title":"The impact of glycosylation on the biological function and structure of human immunoglobulins","volume":"25","author":"Arnold","year":"2007","journal-title":"Annu Rev Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.21408","article-title":"Human plasma IgG N-Glycome profiles reveal a proinflammatory phenotype in chronic thromboembolic pulmonary hypertension","volume":"80","author":"Zhang","year":"2023","journal-title":"Hypertension"},{"key":"B16","doi-asserted-by":"publisher","first-page":"108201","DOI":"10.1016\/j.biotechadv.2023.108201","article-title":"Modulating antibody effector functions by Fc glycoengineering","volume":"67","author":"Garc\u00eda-Alija","year":"2023","journal-title":"Biotechnol Adv"},{"key":"B17","doi-asserted-by":"publisher","first-page":"108169","DOI":"10.1016\/j.biotechadv.2023.108169","article-title":"IgG glycans in health and disease: Prediction, intervention, prognosis, and therapy","volume":"67","author":"Shkunnikova","year":"2023","journal-title":"Biotechnol Adv"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053","article-title":"World medical association declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"Jama"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama"},{"key":"B20","doi-asserted-by":"publisher","first-page":"M111.010090","DOI":"10.1074\/mcp.M111.010090","article-title":"High throughput isolation and glycosylation analysis of IgG-variability and heritability of the IgG glycome in three isolated human populations","volume":"10","author":"Puci\u0107","year":"2011","journal-title":"Mol Cell Proteomics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3791\/60104","article-title":"Immunoglobulin G N-Glycan analysis by ultra-performance liquid chromatography","volume":"155","author":"Liu","year":"2020","journal-title":"J Vis Exp"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01121-z","article-title":"Identification of shared and disease-specific host gene-microbiome associations across human diseases using multi-omic integration","volume":"7","author":"Priya","year":"2022","journal-title":"Nat Microbiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1186\/1471-2458-13-936","article-title":"Rationale, design and methods for a community-based study of clustering and cumulative effects of chronic disease processes and their effects on ageing: the Busselton healthy ageing study","volume":"13","author":"James","year":"2013","journal-title":"BMC Public Health"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2019.0075","article-title":"Type 2 Diabetes Mellitus is associated with the immunoglobulin G N-Glycome through putative proinflammatory mechanisms in an Australian Population","volume":"23","author":"Li","year":"2019","journal-title":"Omics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"119891","DOI":"10.1016\/j.cca.2024.119891","article-title":"Biomarkers in sepsis","volume":"562","author":"Saxena","year":"2024","journal-title":"Clinica Chimica Acta; Int J Clin Chem"},{"key":"B26","doi-asserted-by":"publisher","first-page":"101890","DOI":"10.1016\/j.smim.2024.101890","article-title":"High-throughput N-glycan analysis in aging and inflammaging: State of the art and future directions","volume":"73","author":"Cindri\u0107","year":"2024","journal-title":"Semin In Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(23)00330-2","article-title":"Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine","volume":"12","author":"Cajander","year":"2024","journal-title":"Lancet Respir Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149491","article-title":"Altered IgG glycosylation at COVID-19 diagnosis predicts disease severity","volume":"52","author":"Vicente","year":"2022","journal-title":"Eur J Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13061016","article-title":"IgG N-glycan signatures as potential diagnostic and prognostic biomarkers","volume":"13","author":"Haslund-Gourley","year":"2023","journal-title":"Diagn (Basel)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax0301","article-title":"Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases","volume":"6","author":"Klari\u0107","year":"2020","journal-title":"Sci Adv"},{"key":"B31","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.eng.2022.08.007","article-title":"Differences in Immunoglobulin G glycosylation between influenza and COVID-19 patients","volume":"26","author":"Kljakovi\u0107-Ga\u0161pi\u0107-Batinjan","year":"2022","journal-title":"Engineering"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.146","article-title":"Differential antibody glycosylation in autoimmunity: sweet biomarker or modulator of disease activity","volume":"13","author":"Seeling","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1257906","article-title":"Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study","volume":"14","author":"Lu","year":"2023","journal-title":"Front In Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41590-020-00828-7","article-title":"Proinflammatory IgG Fc structures in patients with severe COVID-19","volume":"22","author":"Chakraborty","year":"2021","journal-title":"Nat Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2024.05.077","article-title":"Prognostic value of plasma immunoglobulin G N-Glycome traits in pulmonary arterial hypertension","volume":"84","author":"Zhang","year":"2024","journal-title":"J Am Coll Cardiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000006135","article-title":"Surviving sepsis campaign research priorities 2023","volume":"52","author":"De Backer","year":"2024","journal-title":"Crit Care Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/s13054-024-04943-x","article-title":"Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis","volume":"28","author":"Evrard","year":"2024","journal-title":"Crit Care (London England)"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/biom13060954","article-title":"Anti-TNF biologicals enhance the anti-inflammatory properties of IgG N-Glycome in Crohn\u2019s Disease","volume":"13","author":"Hani\u0107","year":"2023","journal-title":"Biomolecules"},{"key":"B39","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1186\/s13054-023-04777-z","article-title":"Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis","volume":"27","author":"Wang","year":"2023","journal-title":"Crit Care (London England)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/nicc.13016","article-title":"Prognostic accuracy of SOFA, MEWS, and SIRS criteria in predicting the mortality rate of patients with sepsis: A Meta-analysis","volume":"29","author":"Lan","year":"2023","journal-title":"Nurs In Crit Care"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1532145\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:18:14Z","timestamp":1742195894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1532145\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":40,"alternative-id":["10.3389\/fimmu.2025.1532145"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1532145","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"article-number":"1532145"}}