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We previously showed decreased antibody response following SARS\u2010CoV\u20102 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti\u2010spike (S) IgG1 glycosylation patterns following SARS\u2010CoV\u20102 vaccination in DS and healthy controls (HC). Total and anti\u2010Spike IgG1 Fc N<jats:italic>\u2010<\/jats:italic>glycan glycoprofiles were measured in non\u2010exposed adults with DS and controls before and after SARS\u2010CoV\u20102 vaccination by liquid chromatography\u2013mass spectrometry (LC\u2013MS) of Fc glycopeptides. We recruited <jats:italic>N<\/jats:italic>\u2009=\u200944 patients and <jats:italic>N<\/jats:italic>\u2009=\u200940 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti\u2010S IgG1 with age. In contrast, anti\u2010S IgG1 of DS and HC showed highly comparable glycosylation profiles 28\u2009days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease Fc\u03b3RIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and\/or vaccination schedules.<\/jats:p>","DOI":"10.1111\/acel.14167","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T07:56:48Z","timestamp":1713167808000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>IgG1<\/scp> glycosylation highlights premature aging in Down syndrome"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4841-3180","authenticated-orcid":false,"given":"Bianca M. M.","family":"Streng","sequence":"first","affiliation":[{"name":"Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Van\u00a0Coillie","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Center, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne G.","family":"Wildenbeest","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob S.","family":"Binnendijk","sequence":"additional","affiliation":[{"name":"Centre for Immunology of Infectious Diseases and Vaccines National Institute of Public Health and the Environment  Bilthoven The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaby","family":"Smits","sequence":"additional","affiliation":[{"name":"Centre for Immunology of Infectious Diseases and Vaccines National Institute of Public Health and the Environment  Bilthoven The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerco","family":"den\u00a0Hartog","sequence":"additional","affiliation":[{"name":"Centre for Immunology of Infectious Diseases and Vaccines National Institute of Public Health and the Environment  Bilthoven The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center  Leiden 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":"Federica","family":"Linty","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Center, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remco","family":"Visser","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Center, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":"Gestur","family":"Vidarsson","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Center, University of Amsterdam  Amsterdam The 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