{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:14:34Z","timestamp":1793157274800,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"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>Idiopathic inflammatory myopathies (IIMs) frequently involve interstitial lung disease (ILD), a major contributor to morbidity and mortality. However, the immunological heterogeneity across radiologic ILD subtypes remains poorly defined. This study aimed to explore whether subclass-specific IgG N-glycopeptides could distinguish high-resolution computed tomography (HRCT)-based ILD patterns in IIM patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed plasma IgG subclass-specific N-glycopeptides in 145 IIM patients, including 98 with ILD (IIM-ILD), using intact glycopeptide mass spectrometry. Among IIM-ILD patients, 82 with available HRCT scans were classified into the three predominant subtypes: fibrotic nonspecific interstitial pneumonia (fNSIP, n=40), cellular NSIP (cNSIP, n=18), and organizing pneumonia (OP, n=24). A weighted multinomial logistic regression model was constructed using LASSO-selected glycopeptides and clinical variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifteen intact N-glycopeptides (IGPs) were quantified across all IIM patients. Compared to patients without ILD, IIM-ILD patients showed significant alterations in six IgG2-subclass IGPs. Crucially, distinct glycoform signatures were identified across the three HRCT subtypes: cNSIP was enriched in highly sialylated IgG2 forms; fNSIP showed elevated IgG1 and IgG3 glycoforms; and OP exhibited uniquely high IgG2-N5H4F1. These glycoforms correlated significantly with autoantibody profiles and clinical features. A multinomial logistic regression model integrating seven key IGPs and seven clinical variables achieved robust classification of the HRCT subtypes (macro-averaged AUC = 0.89).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Subclass-specific IgG N-glycosylation profiles reflect the immunological heterogeneity underlying IIM-ILD. Integrating these glycan signatures with routine clinical data creates a strong model for distinguishing HRCT-defined endotypes, supporting their potential to improve disease classification and guide future mechanistic research in autoimmune-related ILD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1696126","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:22:57Z","timestamp":1762150977000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IgG subclass-specific N-glycosylation differentiates HRCT subtypes in idiopathic inflammatory myopathies-associated ILD"],"prefix":"10.3389","volume":"16","author":[{"given":"Tong","family":"Wu","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":"Yubin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinlan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41572-021-00321-x","article-title":"Idiopathic inflammatory myopathies","volume":"7","author":"Lundberg","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(24)00267-4","article-title":"Idiopathic inflammatory myopathies related lung disease in adults","volume":"13","author":"Sehgal","year":"2025","journal-title":"Lancet Respir Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1164\/ajrccm.165.2.ats01","article-title":"This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001","volume":"165","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"220210","DOI":"10.1183\/16000617.0210-2022","article-title":"Prevalence, imaging patterns and risk factors of interstitial lung disease in connective tissue disease: a systematic review and meta-analysis","volume":"32","author":"Joy","year":"2023","journal-title":"Eur Respir review: an Off J Eur Respir Soc"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00520","article-title":"IgG subclasses and allotypes: from structure to effector functions","volume":"5","author":"Vidarsson","year":"2014","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1304365","article-title":"Impact of structural modifications of IgG antibodies on effector functions","volume":"14","author":"Damelang","year":"2023","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1538219","article-title":"N-glycosylation patterns of plasma immunoglobulin G in anti-synthetase syndrome disease","volume":"16","author":"Zhao","year":"2025","journal-title":"Front Immunol"},{"key":"B8","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":"B9","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13075-025-03505-y","article-title":"Profiling of IgG N-glycosylation for axial spondyloarthritis and other rheumatic diseases","volume":"27","author":"Xu","year":"2025","journal-title":"Arthritis Res Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(91)70153-S","article-title":"Amyopathic dermatomyositis (dermatomyositis sin\u00e9 myositis). 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