26rhk04210.3205/26rhk042urn:nbn:de:0183-26rhk0423Meeting AbstractChanges in glycosylation of anti-Ro52 IgG and total IgG are linked to autoimmune congenital heart blockStefanskiStefanskiAna-LuisaALDeutsches Rheumaforschungszentrum (DRFZ), Berlin, DeutschlandCharité – Universitätsmedizin Berlin, Rheumatology and Clinical Immunology, Berlin, DeutschlandauthorWenWenHuihongHLeiden University Medical Center, Department of Rheumatology, Leiden, NiederlandeauthorNoutaNoutaJanJLeiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, NiederlandeauthorDressler-SteinbachDressler-SteinbachIrisICharité – Universitätsmedizin Berlin, Department of Obstetrics, Berlin, DeutschlandauthorBedeiBedeiIvonneIJustus Liebig University Giessen, Department of Prenatal Medicine and Fetal Therapy, Gießen, DeutschlandauthorSachsSachsUlrichUJustus Liebig Universität, Institut für Klinische Immunologie, Transfusionsmedizin und Hämostaseologie, Gießen, DeutschlandauthorToesToesRene E. M.REMLeiden University Medical Center, Department of Rheumatology, Leiden, NiederlandeauthorKrönkeKrönkeGerhardGDeutsches Rheumaforschungszentrum (DRFZ), Berlin, DeutschlandCharité – Universitätsmedizin Berlin, Rheumatology and Clinical Immunology, Berlin, DeutschlandauthorHenrichHenrichWolfgangWCharité – Universitätsmedizin Berlin, Department of Obstetrics, Berlin, DeutschlandauthorSchererSchererHans UHULeiden University Medical Center, Department of Rheumatology, Leiden, NiederlandeauthorWuhrerWuhrerManfredMLeiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, NiederlandeauthorSuurmondSuurmondJolienJLeiden University Medical Center, Department of Rheumatology, Leiden, NiederlandeauthorDörnerDörnerThomasTCharité – Universitätsmedizin Berlin, Rheumatology and Clinical Immunology, Berlin, DeutschlandDeutsches Rheumaforschungszentrum (DRFZ), Berlin, DeutschlandauthorGerman Medical Science GMS Publishing House
Düsseldorf
61020260909englThis is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License.Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung).M0656042Deutsche Gesellschaft für RheumatologieDeutsche Gesellschaft für Orthopädische RheumatologieGesellschaft für Kinder- und Jugendrheumatologie54. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh), 36. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 40. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)Deutscher Rheumatologiekongress 2026Experimentelle & Translationale RheumatologieLeipzig2026090920260912ET.18TextIntroduction: Congenital autoimmune heart block (CHB) is a rare disorder caused by transplacental transfer of maternal anti-Ro/SSA and anti-La/SSB autoantibodies. Alterations in IgG Fc N-linked glycosylation, characteristic of many systemic autoimmune diseases, are markedly influenced by pregnancy . However, their role in congenital heart block in neonates of anti-SSA–positive women remains unclear.Methods: IgG Fc glycosylation composition (Figure 1A ) of antigen-specific (anti-Ro52-, anti-Ro60- and anti-La-IgG) as well as of total IgG was analyzed by an immunosorbent assay followed by liquid chromatography-mass spectrometry . Plasma from 12 pregnant women experiencing a CHB complication, 28 pregnancies positive for anti-Ro/SS-A antibodies without CHB (at-risk) and 18 healthy pregnant women were processed and analyzed accordingly.Results: Total IgG glycosylation in CHB pregnancies exhibited significantly lower galactosylation and sialylation levels compared with at-risk and healthy pregnancies (Figure 1B ). Regarding antigen-specific autoantibodies, anti-Ro52 IgG Fc glycosylation showed higher agalactosylated (G0) and lower GlcNAc bisection levels in CHB compared with at-risk pregnancies (Figure 1C ), while no changes were observed in anti-Ro60 and anti-La IgG Fc glycosylation. Interestingly, while for total IgG the Fc glycosylation differences persisted also postpartum between the groups, this was not the case with respect to antigen-specific anti-Ro52 IgG.Conclusion: This study provides the first evidence linking CHB to Fc glycosylation profiles of maternal anti-Ro52 IgG and total IgG during pregnancy. Although IgG glycosylation is complex and poorly understood, these findings provide new insights into CHB pathogenesis and may help identify high-risk pregnancies and guide targeted interventions. Future mechanistic studies are needed to elucidate the specific pregnancy-associated tolerogenic mechanisms that may influence the composition of Fc glycopeptides.Bondt ARombouts YSelman MHHensbergen PJReiding KRHazes JMDolhain RJWuhrer MImmunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes2014Mol Cell Proteomics3029-39Bondt A, Rombouts Y, Selman MH, Hensbergen PJ, Reiding KR, Hazes JM, Dolhain RJ, Wuhrer M. Immunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes. Mol Cell Proteomics. 2014 Nov;13(11):3029-39. DOI: 10.1074/mcp.M114.039537http://dx.doi.org/10.1074/mcp.M114.039537Falck DWuhrer MGlYcoLISA: antigen-specific and subclass-specific IgG Fc glycosylation analysis based on an immunosorbent assay with an LC-MS readout2024Nat Protoc1887-1909Falck D, Wuhrer M. GlYcoLISA: antigen-specific and subclass-specific IgG Fc glycosylation analysis based on an immunosorbent assay with an LC-MS readout. Nat Protoc. 2024 Jun;19(6):1887-1909. DOI: 10.1038/s41596-024-00963-7http://dx.doi.org/10.1038/s41596-024-00963-7011
Figure 1: (A) Schematic glycosylation composition of IgG Fc part. (B) Significant changes in glycosylation of total IgG and (C) anti-Ro52-Ab between at-risk and CHB pregnancies.AR = at-risk, CHB = congenital heart block. G0 = agalactosylated