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Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns in a prospective cohort of patients with IgG4\u2010RD and the relationship with disease activity and response to treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed IgG Fc\u2010tail and Fab\u2010arm glycosylation status in patients with IgG4\u2010RD (<jats:italic>n<\/jats:italic>\u00a0=\u00a022), disease controls with primary sclerosing cholangitis (PSC) (<jats:italic>n<\/jats:italic>\u00a0=\u00a022), and healthy controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a022). Serum IgG and subclasses were quantified using ELISA. Fc and Fab glycosylation were analyzed by mass spectrometry and lectin affinity chromatography, respectively. Disease activity, organ damage, and response to treatment were assessed using the IgG4 Responder Index.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunoglobulin G Fab sialylation was increased in IgG4\u2010RD compared with PSC and healthy control (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01), with a preferential increase in IgG4\u2010specific Fab sialylation, which was independent of IgG4 Fab\u2010arm exchange. There was a reduction in IgG1\u2010specific Fc bisection and hybrid structures in IgG4\u2010RD (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), which recovered upon steroid treatment and correlated with disease activity. Overall, IgG Fc galactosylation was reduced in both IgG4\u2010RD and PSC (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), with a preferential reduction in IgG1\u2010specific sialylation and enhancement of IgG4\u2010specific bisection in PSC. IgG4 fucosylation and IgG1\/2\/3 hybrid structures negatively correlated with complement C3 and C4 levels in IgG4\u2010RD (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), but not PSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report the first study showing unique antibody glycosylation status in a prospective cohort of IgG4\u2010RD and PSC patients, which may determine modulation of the immune system and contribute to disease pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14512","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T04:30:01Z","timestamp":1540182601000},"page":"1878-1886","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Unique patterns of glycosylation in immunoglobulin subclass G4\u2010related disease and primary sclerosing cholangitis"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-8392","authenticated-orcid":false,"given":"Emma L","family":"Culver","sequence":"first","affiliation":[{"name":"Translational Gastroenterology Unit and Oxford NIHR Biomedical Research Centre John Radcliffe Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fleur S","family":"van de Bovenkamp","sequence":"additional","affiliation":[{"name":"Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninotska I L","family":"Derksen","sequence":"additional","affiliation":[{"name":"Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Koers","sequence":"additional","affiliation":[{"name":"Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamsin","family":"Cargill","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit and Oxford NIHR Biomedical Research Centre John Radcliffe Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Barnes","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology Unit and Oxford NIHR Biomedical Research Centre John Radcliffe Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A","family":"de Neef","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolien A M","family":"Koeleman","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob C","family":"Aalberse","sequence":"additional","affiliation":[{"name":"Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Wuhrer","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Rispens","sequence":"additional","affiliation":[{"name":"Sanquin Research, Department of 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