{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:59:17Z","timestamp":1791237557524,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development, and Innovation Office","award":["NKFIH K-119459"],"award-info":[{"award-number":["NKFIH K-119459"]}]},{"name":"National Research, Development, and Innovation Office","award":["NKFIH K-128546"],"award-info":[{"award-number":["NKFIH K-128546"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis. In addition, 60\u201380% of patients express anti-citrullinated protein antibodies (ACPAs), which serve as a diagnostic marker for RA. The effector functions of these autoantibodies can be heavily affected by the N-glycosylation of their Fc region. Here we present a comparison of the Fc N-glycosylation of ACPA IgG to that of non-ACPA IgG from the same patients, and of healthy controls, in an IgG isoform-specific manner. We isolated ACPA and normal serum IgG, digested by trypsin, and separated the resulting peptide mixture by a reversed-phase nanoLC coupled to a Bruker Maxis II Q-TOF, and determined the relative abundance of glycoforms. The paired analysis of galactosylation and sialylation of the IgG subclasses of ACPA and non-ACPA IgG has shown a significant, moderate negative correlation with the inflammatory markers, the level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as with rheuma-factor (RF), but not with the disease activity score (DAS) or cyclic citrullinated peptide specific antibodies (anti-CCP). However, we detected a significant negative correlation between glycosylation and DAS in the non-ACPA IgG fractions. Furthermore, the isoform-specific analysis revealed additional insight into the changes of the glycosylation features of IgG in RA: changes in the frequencies of the bisecting GlcNAc unit between sample groups could be explained by only the IgG1 isoform; while invariance in fucosylation is the result of the superposition of two isoforms with opposite changes. These results highlight the importance of analyzing immunoglobulin glycosylation in an isoform-specific manner.<\/jats:p>","DOI":"10.3390\/ijms26199626","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:38:08Z","timestamp":1759397888000},"page":"9626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immunoglobulin G Subclass-Specific Glycosylation Changes in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-395X","authenticated-orcid":false,"given":"D\u00e1niel","family":"Szab\u00f3","sequence":"first","affiliation":[{"name":"MS Proteomics Research Group, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"},{"name":"Hevesy Gy\u00f6rgy PhD School of Chemistry, Faculty of Science, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3809-6541","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Gyebrovszki","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Szarka","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fel\u00edcia","family":"Auer","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"},{"name":"Translational Glycomics Research Group, University of Pannonia, 8200 Veszpr\u00e9m, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Rojkovich","sequence":"additional","affiliation":[{"name":"Rheumatology-Rehabilitation Department, Buda Hospital of the Hospitaller Order of Saint John of God, 1027 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Semmelweis University, 1085 Budapest, Hungary"},{"name":"Heart and Vascular Centre, Semmelweis University, 1085 Budapest, Hungary"},{"name":"Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Telekes","sequence":"additional","affiliation":[{"name":"Department of Oncology, St Lazarus County Hospital, 3100 Salg\u00f3tarj\u00e1n, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1roly","family":"V\u00e9key","sequence":"additional","affiliation":[{"name":"MS Proteomics Research Group, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-6652","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Drahos","sequence":"additional","affiliation":[{"name":"MS Proteomics Research Group, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"\u00c1cs","sequence":"additional","affiliation":[{"name":"MS Proteomics Research Group, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"S\u00e1rmay","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00296-020-04731-0","article-title":"The Global Prevalence of Rheumatoid Arthritis: A Meta-Analysis Based on a Systematic Review","volume":"41","author":"Almutairi","year":"2021","journal-title":"Rheumatol. 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