{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:29Z","timestamp":1787034329335,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) characterized by immune dysregulation and kidney inflammation. Alterations in immunoglobulin G (IgG) glycosylation are known to influence immune responses and have been implicated in autoimmune diseases, including SLE and LN. This study aimed to investigate longitudinal changes in IgG glycosylation in patients with active LN, from before treatment to one year after immunosuppressive therapy initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum samples were collected from 17 patients with LN at two time points, i.e., at active LN, prior to treatment initiation (baseline), and after 12 months of therapy. IgG was purified and subjected to detailed glycosylation analysis (total and fragment-specific) by capillary gel electrophoresis (CGE). Changes in glycosylation patterns between the two time points were assessed using linear mixed effects and regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant alterations in IgG glycosylation were observed between the two time points. In total IgG, decreased sialylation and increased monogalactosylated structures were prominent. Fragment-specific analyses revealed divergent dynamics: the Fc region showed increased asialylation and a higher proportion of bisecting GlcNAc-containing glycans, consistent with a pro-inflammatory effector profile, while the Fab region exhibited increased digalactosylated glycans and decreased fucosylation, a pattern not mirrored in the Fc region or total IgG glycome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings indicate pro-inflammatory longitudinal shifts in IgG glycosylation during the transition of LN from an active to a treated disease state. The study underscores the relevance of IgG glycosylation in LN pathophysiology and suggests that IgG glycosylation patterns change following immunosuppressive therapy for active LN, potentially reflecting ongoing disease-related immune processes despite improvement in conventional clinical parameters.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1886381","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:37:36Z","timestamp":1787031456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IgG glycosylation dynamics in active lupus nephritis during the first year of immunosuppressive therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana","family":"Cindri\u0107","sequence":"first","affiliation":[{"name":"Genos Glycoscience Research Laboratory","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dionysis","family":"Nikolopoulos","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Centre for Molecular Medicine (CMM), Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Sherina","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Centre for Molecular Medicine (CMM), Karolinska Institutet","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frano","family":"Vu\u010dkovi\u0107","sequence":"additional","affiliation":[{"name":"Genos Glycoscience Research Laboratory","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Tamirou","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Cliniques Universitaires Saint-Luc, P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Patenaude","sequence":"additional","affiliation":[{"name":"Genos Glycoscience Research Laboratory","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Pu\u010di\u0107-Bakovi\u0107","sequence":"additional","affiliation":[{"name":"Genos Glycoscience Research Laboratory","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Radovani","family":"Trbojevi\u0107","sequence":"additional","affiliation":[{"name":"Genos Glycoscience Research Laboratory","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric A.","family":"Houssiau","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Cliniques Universitaires Saint-Luc, P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordan","family":"Lauc","sequence":"additional","affiliation":[{"name":"Genos Glycoscience Research Laboratory","place":["Zagreb, Croatia"]},{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Parodis","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Centre for Molecular Medicine (CMM), Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital","place":["Stockholm, Sweden"]},{"name":"Department of Rheumatology, Faculty of Medicine and Health, \u00d6rebro University","place":["\u00d6rebro, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203320932219","article-title":"Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression","volume":"29","author":"Mahajan","year":"2020","journal-title":"Lupus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41572-025-00653-y","article-title":"Lupus nephritis","volume":"11","author":"Parodis","year":"2025","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.5606\/ArchRheumatol.2017.6127","article-title":"A systematic review and meta-analysis of prevalence of biopsy-proven lupus nephritis","volume":"33","author":"Wang","year":"2018","journal-title":"Arch Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac218","article-title":"Survival analysis of mortality and development of lupus nephritis in patients with systemic lupus erythematosus up to 40 years of follow-up","volume":"62","author":"Luo","year":"2023","journal-title":"Rheumatology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/s41581-023-00722-z","article-title":"Pathogenic cellular and molecular mediators in lupus nephritis","volume":"19","author":"Mohan","year":"2023","journal-title":"Nat Rev Nephrol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e000389","DOI":"10.1136\/lupus-2020-000389","article-title":"Prediction of prognosis and renal outcome in lupus nephritis","volume":"7","author":"Parodis","year":"2020","journal-title":"Lupus Sci Med"},{"key":"B7","article-title":"N-glycans","volume-title":"Essentials of Glycobiology","author":"Stanley","year":"2022"},{"key":"B8","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/82_2019_152","article-title":"IgG Fc glycosylation in human immunity","volume":"423","author":"Wang","year":"2019","journal-title":"Curr Topics Microbiol Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13407","article-title":"The importance of IgG glycosylation\u2014What did we learn after analyzing over 100,000 individuals","volume":"328","author":"Kri\u0161ti\u0107","year":"2024","journal-title":"Immunol Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502136","article-title":"The emerging importance of IgG Fab glycosylation in immunity","volume":"196","author":"van de Bovenkamp","year":"2016","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1177\/0961203314558861","article-title":"Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus","volume":"24","author":"Sj\u00f6wall","year":"2015","journal-title":"Lupus"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/art.39273","article-title":"Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome","volume":"67","author":"Vu\u010dkovi\u0107","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147789","article-title":"Aberrantly glycosylated IgG elicits pathogenic signaling in podocytes and signifies lupus nephritis","volume":"6","author":"Bhargava","year":"2021","journal-title":"JCI Insight"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/art.43200","article-title":"Aberrant glycosylation of IgG in children with active lupus nephritis alters podocyte metabolism and causes podocyte injury","volume":"77","author":"Bhargava","year":"2025","journal-title":"Arthritis Rheumatol (Hoboken N.J.)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102804","article-title":"Antibody glycosylation in autoimmune diseases","volume":"20","author":"Zhou","year":"2021","journal-title":"Autoimmun Rev"},{"key":"B16","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 Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.eng.2023.01.006","article-title":"Serum IgG glycan hallmarks of systemic lupus erythematosus","volume":"26","author":"Pan","year":"2023","journal-title":"Engineering"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.037465","article-title":"Comparative performance of four methods for high-throughput glycosylation analysis of immunoglobulin G in genetic and epidemiological research","volume":"13","author":"Huffman","year":"2014","journal-title":"Mol Cell Proteomics"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01349-z","article-title":"Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome","author":"Vinicki","year":"2024","journal-title":"Geroscience"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13051206","article-title":"Altered IgG N-glycosylation at onset of type 1 diabetes in children is predominantly driven by changes in the Fab N-glycans","volume":"13","author":"Plav\u0161a","year":"2025","journal-title":"Biomedicines"},{"key":"B21","doi-asserted-by":"publisher","first-page":"14770","DOI":"10.1038\/s41598-025-99226-y","article-title":"Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy","volume":"15","author":"Valk","year":"2025","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.10.035","article-title":"Differences in IgG autoantibody Fab glycosylation across autoimmune diseases","volume":"151","author":"Koers","year":"2023","journal-title":"J Allergy Clin Immunol"},{"key":"B23","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":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.841710","article-title":"Changes of IgG N-glycosylation in thyroid autoimmunity: The modulatory effect of methimazole in Graves\u2019 disease and the association with the severity of inflammation in Hashimoto\u2019s thyroiditis","volume":"13","author":"Trzos","year":"2022","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-006-5409-0","article-title":"Galactosylation of IgG from rheumatoid arthritis (RA) patients--changes during therapy","volume":"23","author":"Pasek","year":"2006","journal-title":"Glycoconjugate J"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.20191","article-title":"Effect of infliximab on the glycosylation of IgG of patients with rheumatoid arthritis","volume":"21","author":"Croce","year":"2007","journal-title":"J Clin Lab Anal"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.089292","article-title":"Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory autoimmune arthritis","volume":"68","author":"Van Beneden","year":"2009","journal-title":"Ann Rheumatic Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket189","article-title":"Glycosylation status of serum in inflammatory arthritis in response to anti-TNF treatment","volume":"52","author":"Collins","year":"2013","journal-title":"Rheumatol (Oxford England)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.cellimm.2018.07.009","article-title":"Immunoglobulin G glycosylation in aging and diseases","volume":"333","author":"Gudelj","year":"2018","journal-title":"Cell Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01183","article-title":"Sialylated autoantigen-reactive IgG antibodies attenuate disease development in autoimmune mouse models of lupus nephritis and rheumatoid arthritis","volume":"9","author":"Bartsch","year":"2018","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.kint.2024.10.018","article-title":"Lupus nephritis: redefining the treatment goals","volume":"107","author":"Vriese","year":"2025","journal-title":"Kidney Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.1","article-title":"Long-lived autoreactive plasma cells drive persistent autoimmune inflammation","volume":"7","author":"Hiepe","year":"2011","journal-title":"Nat Rev Rheumatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203455","article-title":"Autoantibodies from long-lived \u2018memory\u2019 plasma cells of NZB\/W mice drive immune complex nephritis","volume":"72","author":"Cheng","year":"2013","journal-title":"Ann Rheumatic Dis"},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-70115-4","volume-title":"The Role of Glycosylation in Health and Disease","author":"Lauc","year":"2021"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glt190","article-title":"Glycans are a novel biomarker of chronological and biological ages","volume":"69","author":"Kri\u0161ti\u0107","year":"2014","journal-title":"J Gerontology - Ser A Biol Sci Med Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103884","article-title":"Global variability of the human IgG glycome","volume":"12","author":"\u0160tambuk","year":"2020","journal-title":"Aging"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/316452a0","article-title":"Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG","volume":"316","author":"Parekh","year":"1985","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"R193","DOI":"10.1186\/ar2892","article-title":"Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study","volume":"11","author":"van de Geijn","year":"2009","journal-title":"Arthritis Res Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1186\/s13075-016-1172-1","article-title":"Fab glycosylation of immunoglobulin G does not associate with improvement of rheumatoid arthritis during pregnancy","volume":"18","author":"Bondt","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"B40","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/s41467-020-14794-z","article-title":"Structural basis for substrate specificity and catalysis of \u03b11,6-fucosyltransferase","volume":"11","author":"Garc\u00eda-Garc\u00eda","year":"2020","journal-title":"Nat Commun"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1021\/ja208390n","article-title":"Chemoenzymatic synthesis and Fc\u03b3 receptor binding of homogeneous glycoforms of antibody Fc domain. Presence of a bisecting sugar moiety enhances the affinity of Fc to Fc\u03b3IIIa receptor","volume":"133","author":"Zou","year":"2011","journal-title":"J Am Chem Soc"},{"key":"B42","doi-asserted-by":"publisher","first-page":"12325","DOI":"10.1038\/s41598-017-12495-0","article-title":"Subclass-specific IgG glycosylation is associated with markers of inflammation and metabolic health","volume":"7","author":"Plomp","year":"2017","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxx025","article-title":"Diversification of IgG effector functions","volume":"29","author":"Bournazos","year":"2017","journal-title":"Int Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2025.101946","article-title":"Variable domain glycosylation as a marker and modulator of immune responses: Insights into autoimmunity and B-cell Malignancies","volume":"78","author":"Biersteker","year":"2025","journal-title":"Semin Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm1759","article-title":"Surface Ig variable domain glycosylation affects autoantigen binding and acts as threshold for human autoreactive B cell activation","volume":"8","author":"Kissel","year":"2022","journal-title":"Sci Adv"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.5929","article-title":"The variable domain glycosylation in a monoclonal antibody specific to GnRH modulates antigen binding","volume":"234","author":"Khurana","year":"1997","journal-title":"Biochem Biophys Res Commun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1886381\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:37:37Z","timestamp":1787031457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1886381\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2026.1886381"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1886381","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"article-number":"1886381"}}