{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T14:56:05Z","timestamp":1793804165668,"version":"4.6.1"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office","award":["K 119459"],"award-info":[{"award-number":["K 119459"]}]},{"name":"National Research, Development and Innovation Office","award":["K 128546"],"award-info":[{"award-number":["K 128546"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their capability of inducing TNF\u03b1 production, and furthermore, to analyze the correlations between the composition of Fc glycans and inflammatory markers in RA. We isolated IgG from sera of healthy volunteers and RA patients, and purified ACPAs on a citrulline-peptide column. Immunocomplexes (IC) were formed by adding an F(ab)2 fragment of anti-human IgG. U937 cells were used to monitor the binding of IC to Fc\u03b3R and to trigger TNF\u03b1 release determined by ELISA. To analyze glycan profiles, control IgG and ACPA-IgG were digested with trypsin and the glycosylation patterns of glycopeptides were analyzed by determining site-specific N-glycosylation using nano-UHPLC-MS\/MS. We found that both sialylation and galactosylation levels of ACPA-IgG negatively correlate with inflammation-related parameters such as CRP, ESR, and RF. Functional assays show that dimerized ACPA-IgG significantly enhances TNF\u03b1 release in an Fc\u03b3RI-dependent manner, whereas healthy IgG does not. TNF\u03b1 production inversely correlates with the relative intensities of the G0 glycoform, which lacks galactose and terminal sialic acid moieties.<\/jats:p>","DOI":"10.3390\/ijms23105828","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T22:57:22Z","timestamp":1653346642000},"page":"5828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3809-6541","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Gyebrovszki","sequence":"first","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"\u00c1cs","sequence":"additional","affiliation":[{"name":"MS Proteomics Research Group, Research Centre for Natural Sciences, E\u00f6tv\u00f6s Lor\u00e1nd Research Network, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-395X","authenticated-orcid":false,"given":"D\u00e1niel","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"MS Proteomics Research Group, Research Centre for Natural Sciences, E\u00f6tv\u00f6s Lor\u00e1nd Research Network, 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"}]},{"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, Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, 8200 Veszpr\u00e9m, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soma","family":"Novoz\u00e1nszki","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University, 1117 Budapest, Hungary"},{"name":"Central Laboratory-Microbiology Profile, Molecular Department, National Institute of Hematology and Infectious Diseases, Central Hospital of Southern Pest, 1097 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Rojkovich","sequence":"additional","affiliation":[{"name":"Rheumatology Department III, Polyclinic of the Hospitaller Brothers of St. John of God, 1027 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Magyar","sequence":"additional","affiliation":[{"name":"ELKH-ELTE Research Group of Peptide Chemistry, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Hudecz","sequence":"additional","affiliation":[{"name":"ELKH-ELTE Research Group of Peptide Chemistry, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1roly","family":"V\u00e9key","sequence":"additional","affiliation":[{"name":"MS Proteomics Research Group, Research Centre for Natural Sciences, E\u00f6tv\u00f6s Lor\u00e1nd Research Network, 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, Research Centre for Natural Sciences, E\u00f6tv\u00f6s Lor\u00e1nd Research Network, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3066-7768","authenticated-orcid":false,"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":[[2022,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ITC1","DOI":"10.7326\/AITC201901010","article-title":"Rheumatoid Arthritis","volume":"170","author":"Sparks","year":"2019","journal-title":"Ann. 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A"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/10\/5828\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:16:50Z","timestamp":1760138210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/10\/5828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,23]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23105828"],"URL":"https:\/\/doi.org\/10.3390\/ijms23105828","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,23]]}}}