{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:51:04Z","timestamp":1777866664095,"version":"3.51.4"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430362220003"],"award-info":[{"award-number":["10430362220003"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n N<\/jats:italic>\n \u2010glycosylation drives immunoglobulin G (IgG) stability and function, directly affecting immune response. However, the effect of demographic and modifiable lifestyle factors on IgG\n N<\/jats:italic>\n \u2010glycosylation in the general population remains poorly characterized.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This study investigated the effects of age, sex, smoking, alcohol, body mass index (BMI), and time on IgG Fc\n N<\/jats:italic>\n \u2010glycosylation patterns in the population\u2010based Rotterdam Study. IgG1\u20134 compositions were quantified by nanoflow liquid chromatography\u2013electrospray ionization\u2013mass spectrometry (nano\u2013LC\u2013ESI\u2013MS) and expressed as percentages of the total signal. Cross\u2010sectional associations were assessed using the confounder\u2010adjusted multiple linear regression, while longitudinal changes were evaluated using the mixed effects models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This study included 8242 participants (mean age\u2009=\u200964.2\u2009years) with repeated measurements for 448 participants (mean follow\u2010up\u2009=\u20095.6\u2009years). Age and BMI were associated with increased bisection and fucosylation (\u03b2\u2009=\u20090.007\u20130.030 SD\/unit increase) and decreased galactosylation and sialylation (\u03b2\u2009=\u2009\u22120.007 to \u22120.057 SD). Women demonstrated higher bisection (\u03b2\u2009=\u20090.102\u20130.329 SD) across all subclasses, lower galactosylation, and sialylation in IgG\n 1<\/jats:sub>\n \u2010\n 3<\/jats:sub>\n (\u03b2\u2009=\u2009\u22120.042 to \u22120.138 SD), but higher levels in IgG\n 4<\/jats:sub>\n (\u03b2\u2009=\u20090.062\u20130.070 SD), and pronounced changes between 45 to 55\u2009years. Smoking (\u03b2\u2009=\u20090.621 to 0.825 SD) and alcohol were associated with increased bisection, with a gradient effect in smoking status. With time, galactosylation and sialylation declined (\u03b2\u2009=\u2009\u22120.055 to \u22120.087 SD\/year), while bisection increased (\u03b2\u2009=\u20090.030 to 0.050 SD\/year).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Aging, higher BMI, female sex, smoking, and heavy alcohol consumption are key determinants of IgG\n N<\/jats:italic>\n \u2010glycome patterns, which are indicative of inflammation. Over time, glycan compositions demonstrate a gradual change toward a pro\u2010inflammatory phenotype in a sex\u2010related manner.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/all.70361","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:06:27Z","timestamp":1777539987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determinants of Immunoglobulin\u2010G N\u2010Glycan Patterns in the Aging General Population"],"prefix":"10.1111","author":[{"given":"Samantha","family":"Leonard","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Allergy & Clinical Immunology Erasmus MC University Medical Center Rotterdam the Netherlands"},{"name":"Department of Epidemiology Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Heijmans","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Allergy & Clinical Immunology Erasmus MC University Medical Center Rotterdam the Netherlands"},{"name":"Department of Epidemiology Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virgil A. S. H.","family":"Dalm","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Allergy & Clinical Immunology Erasmus MC University Medical Center Rotterdam the Netherlands"},{"name":"Department of Immunology Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvan","family":"Licher","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus MC University Medical Center Rotterdam the Netherlands"},{"name":"Department of Primary Care Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Nouta","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steinar","family":"Gijze","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Falck","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Martin","family":"van Hagen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Allergy & Clinical Immunology Erasmus MC University Medical Center Rotterdam the Netherlands"},{"name":"Department of Immunology Erasmus MC University Medical Center Rotterdam the Netherlands"},{"name":"Center of Excellence for Allergy and Clinical Immunology, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Faculty of Medicine Chulalongkorn University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Peeters","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-4995","authenticated-orcid":false,"given":"Manfred","family":"Wuhrer","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Layal","family":"Chaker","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus MC University Medical Center Rotterdam the Netherlands"},{"name":"Department of Internal Medicine, Division of Endocrinology Erasmus MC University Medical Center Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biotechadv.2023.108169","article-title":"IgG Glycans in Health and Disease: Prediction, Intervention, Prognosis, and Therapy","volume":"67","author":"Shkunnikova S.","year":"2023","journal-title":"Biotechnology Advances"},{"issue":"4","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.coi.2008.06.007","article-title":"Terminal Sugars of Fc Glycans Influence Antibody Effector Functions of IgGs","volume":"20","author":"Raju T. 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