Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy
Several chronic autoimmune diseases are characterized by elevated autoantibody Fab glycosylation. Whether Fab glycans link to disease state or development remains unclear, yet may serve as a marker thereof. Many autoimmune diseases are treated with B cell depletion therapies that particularly result in a decline of autoantibodies. The question arises whether B cell depletion therapy may have an impact on Fab glycosylation. Here, we investigated the longitudinal effects of B cell depletion therapy on Fab glycosylation of total IgG and IgG autoantibodies in rheumatoid arthritis (RA), pemphigus vulgaris (PV), ANCA-associated vasculitis (AAV), and multiple sclerosis (MS). Baseline Fab glycosylation was compared to 6-12 months into therapy by lectin affinity chromatography, determining Fab sialylation as an estimate of Fab glycosylation. We observed a modest decrease in Fab glycosylation of total IgG for RA (median 13.8%[IQR 11.7-16.3] - 9.1%[IQR8-11]) and PV (16.4%[IQR14.9-17.5] - 13.01%[IQR10.8-15.5]) after 6 months, whereas for AAV Fab glycosylation slightly increased (11.6%[IQR7.4-15] - 14.9%[IQR11.4-19.3]), and no changes were found for MS. Autoantibody titers (anti-CCP, anti-PR3, anti-Dsg3) had declined following B cell depletion therapy, yet their elevated Fab glycosylation levels were maintained. Taken together, Fab glycosylation levels of autoantibodies do not decrease upon B cell depletion therapy, thereby retaining their predictive potential as biomarker.
Authors
- S. Marieke van Ham (ORCID: https://orcid.org/0000-0003-1999-9494)
- Taco W. Kuijpers (ORCID: https://orcid.org/0000-0002-7421-3370)
- Diane van der Woude (ORCID: https://orcid.org/0000-0001-8121-5879)
- Jana Koers (ORCID: https://orcid.org/0000-0002-1451-9642)
- Anika M. Valk (ORCID: https://orcid.org/0009-0005-8712-8959)
- René E. M. Toes (ORCID: https://orcid.org/0000-0002-9618-6414)
- Theo Rispens (ORCID: https://orcid.org/0000-0001-9600-1312)
- Barbara Horváth (ORCID: https://orcid.org/0000-0001-8559-3674)
- Zoé van Kempen
- Peter Heeringa (ORCID: https://orcid.org/0000-0001-8684-763X)
- Abraham Rutgers (ORCID: https://orcid.org/0000-0002-1641-6890)
- Laura Hogenboom (ORCID: https://orcid.org/0009-0005-1230-1366)
- Nicolaas A. Bos (ORCID: https://orcid.org/0000-0002-8649-0455)
- Joep Killestein (ORCID: https://orcid.org/0000-0002-6347-5957)
- Anja ten Brinke (ORCID: https://orcid.org/0000-0002-0135-7496)
- Ninotska I. L. Derksen (ORCID: https://orcid.org/0000-0002-0189-2675)
Institutions
- University Medical Center Groningen (NL)
- University of Groningen (NL)
- Maastricht School of Management (NL)
- Leiden University Medical Center (NL)
- Maastricht University Medical Centre (NL)
- Erasmus MC (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Sanquin (NL)
- Maastricht University (NL)
- Emma Kinderziekenhuis (NL)
- National Institute for Public Health and the Environment (NL)
- Amsterdam Neuroscience (NL)
- Willem-Alexander Kinderziekenhuis (NL)
- Amsterdam University Medical Centers (NL)
- Vrije Universiteit Amsterdam (NL)
- University of Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-04-28
- DOI
- https://doi.org/10.1038/s41598-025-99226-y
- Citations
- 2
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 2.72
Funders
- Vasculitis Foundation
- Landsteiner Foundation for Blood Transfusion Research
- Universiteit van Amsterdam