{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:14:38Z","timestamp":1793157278444,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"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>Introduction<\/jats:title><jats:p>Anti-synthetase syndrome (ASS) is a subtype of idiopathic inflammatory myopathy (IIM) characterized by characteristic rash, myositis, and interstitial lung disease (ILD). The etiology of ASS is unknown, and patients have a poor quality of life and are prone to pulmonary infection. Recent studies have elucidated the potential role of abnormal glycosylation of immunoglobulin G (IgG) in the pathogenesis of autoimmune diseases. However, the pattern of patient-specific IgG N-glycosylation in ASS has not been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>the GlycoQuant method was used to quantify the intact N-glycopeptides of IgG from 30 ASS patients and 30 healthy controls (HCs). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>Thirteen differentially expressed intact N-glycopeptides were identified (p&amp;lt;0.05). Notably, we observed increased fucosylation (p&amp;lt;0.0001) and decreased N-acetylneuraminic acid (p&amp;lt;0.05) in ASS patients. In addition, specific glycosylation patterns correlated with lung function parameters. Our study revealed the IgG glycosylation profile in ASS patients and provided a valuable reference for further investigation of its potential diagnostic and prognostic applications.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1538219","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T09:15:43Z","timestamp":1750238143000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["N-glycosylation patterns of plasma immunoglobulin G in anti-synthetase syndrome disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Jing","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinlan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00321-x","article-title":"Idiopathic inflammatory myopathies","author":"Lundberg","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/CPM.0000000000000171","article-title":"The diagnosis and treatment of antisynthetase syndrome","author":"Witt","year":"2016","journal-title":"Clin Pulm Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(90)90149-8","article-title":"Clinical manifestations in patients with antibody to PL-12 antigen (alanyl-tRNA synthetase)","author":"Targoff","year":"1990","journal-title":"Am J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.4.2315","article-title":"Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease","author":"Hirakata","year":"1999","journal-title":"J Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085062","article-title":"The multicenter study of a new assay for simultaneous detection of multiple anti-aminoacyl-tRNA synthetases in myositis and interstitial pneumonia","author":"Nakashima","year":"2014","journal-title":"PLoS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1170818","article-title":"Editorial: New methods, techniques and applications in clinical glycoproteomics","volume":"10","author":"Zhang","year":"2023","journal-title":"Front Mol Biosci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.v5.10","article-title":"Clinical glycoproteomics: methods and diseases","author":"Wang","year":"2024","journal-title":"MedComm (2020)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.O116.058503","article-title":"Recent advances in clinical glycoproteomics of immunoglobulins (Igs)","author":"Plomp","year":"2016","journal-title":"Mol Cell Proteomics"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.09.046","article-title":"Structure and function of immunoglobulins","author":"Schroeder","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1013990","article-title":"Site-specific N-glycosylation characterization of micro monoclonal immunoglobulins based on EThcD-sceHCD-MS\/MS","volume":"13","author":"Luo","year":"2022","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12014-024-09522-4","article-title":"Quantitative site-specific N-glycosylation analysis reveals IgG glyco-signatures for pancreatic cancer diagnosis","author":"Jin","year":"2024","journal-title":"Clin Proteomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.cell.2016.08.072","article-title":"A functional role for antibodies in tuberculosis","author":"Lu","year":"2016","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(96)90124-8","article-title":"Raised levels of agalactosyl IgG in childhood tuberculosis","author":"Pilkington","year":"1996","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"B14","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","author":"Sj\u00f6wall","year":"2015","journal-title":"Lupus"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.03.018","article-title":"Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up","author":"Gudelj","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1053\/j.gastro.2018.01.002","article-title":"Glycosylation of immunoglobulin G associates with clinical features of inflammatory bowel diseases","author":"\u0160imurina","year":"2018","journal-title":"Gastroenterology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000372","article-title":"Inflammatory bowel disease associates with proinflammatory potential of the immunoglobulin G glycome","author":"Trbojevi\u0107 Akma\u010di\u0107","year":"2015","journal-title":"Inflammation Bowel Dis"},{"key":"B18","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1006\/jaut.1996.0104","article-title":"A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in terminal galactose and N-acetylglucosamine","author":"Bond","year":"1997","journal-title":"J Autoimmun"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.01.033","article-title":"Galactosylation and sialylation levels of igG predict relapse in patients with PR3-ANCA associated vasculitis","volume":"17","author":"Kemna","year":"2017","journal-title":"EBioMedicine"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1021\/pr401213z","article-title":"IgG Fc N-glycosylation in Guillain-Barr\u00e9 syndrome treated with immunoglobulins","author":"Fokkink","year":"2014","journal-title":"J Proteome Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4105","article-title":"Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition","author":"Vaccari","year":"2016","journal-title":"Nat Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu388","article-title":"Aberrant serum immunoglobulin G glycosylation in chronic hepatitis B is associated with histological liver damage and reversible by antiviral therapy","author":"Ho","year":"2015","journal-title":"J Infect Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-024-00850-0","article-title":"The role of antibody glycosylation in autoimmune and alloimmune kidney diseases","author":"Beyze","year":"2024","journal-title":"Nat Rev Nephrol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.5c00253","article-title":"Deciphering N-glycosylation dynamics of serum monoclonal immunoglobulins in multiple myeloma via EThcD-sceHCD-MS\/MS","author":"Li","year":"2025","journal-title":"J Proteome Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"17958","DOI":"10.1038\/s41598-018-36395-z","article-title":"Patients with anti-Jo1 antibodies display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies","author":"Fernandes-Cerqueira","year":"2018","journal-title":"Sci Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1590\/S1806-37132011000100015","article-title":"Myositis-related interstitial lung disease and antisynthetase syndrome","author":"Solomon","year":"2011","journal-title":"J Bras Pneumol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1093\/ndt\/gfab204","article-title":"O-glycoforms of polymeric immunoglobulin A1 in the plasma of patients with IgA nephropathy are associated with pathological phenotypes","author":"Yu","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s43657-023-00150-w","article-title":"A novel integrated pipeline for site-specific quantification of N-glycosylation","author":"Zhao","year":"2024","journal-title":"Phenomics"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202069200","article-title":"Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity","author":"Shields","year":"2002","journal-title":"J Biol Chem"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00877","article-title":"Decoding the human immunoglobulin G-glycan repertoire reveals a spectrum of fc-receptor- and complement-mediated-effector activities","volume":"8","author":"Dekkers","year":"2017","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"339828","DOI":"10.1016\/j.aca.2022.339828","article-title":"N-Glycosylation of monoclonal antibody therapeutics: A comprehensive review on significance and characterization","volume":"1209","author":"Shrivastava","year":"2022","journal-title":"Anal Chim Acta"},{"key":"B32","doi-asserted-by":"publisher","first-page":"103883","DOI":"10.1016\/j.ebiom.2022.103883","article-title":"Fucosylation of anti-dsDNA IgG1 correlates with disease activity of treatment-na\u00efve systemic lupus erythematosus patients","volume":"77","author":"Han","year":"2022","journal-title":"EBioMedicine"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2012.10.028","article-title":"Enhanced expression and fucosylation of ficolin3 in plasma of RA patients","author":"Roy","year":"2013","journal-title":"Clin Biochem"},{"key":"B34","doi-asserted-by":"publisher","first-page":"17","DOI":"10.4161\/mabs.4.1.18347","article-title":"Disulfide bond structures of IgG molecules: structural variations, chemical modifications and possible impacts to stability and biological function","author":"Liu","year":"2012","journal-title":"MAbs"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830130312","article-title":"Simultaneous absence of the human IgG1, IgG2, IgG4 and IgA1 subclasses: immunological and immunogenetical considerations","author":"Lefranc","year":"1983","journal-title":"Eur J Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s12931-024-02851-w","article-title":"Clinical and prognostic associations of anti-Jo-1 antibody levels in patients with antisynthetase syndrome","author":"Yang","year":"2024","journal-title":"Respir Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/art.22865","article-title":"Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy","author":"Stone","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B38","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s41584-022-00867-4","article-title":"Glycobiology of rheumatic diseases","author":"Kissel","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200800760","article-title":"The development of retrosynthetic glycan libraries to profile and classify the human serum N-linked glycome","author":"Kronewitter","year":"2009","journal-title":"Proteomics"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1538219\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T09:15:50Z","timestamp":1750238150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1538219\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2025.1538219"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1538219","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,18]]},"article-number":"1538219"}}