Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy

Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy

Abstract 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 particular...

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Main Authors: Anika M. Valk, Jana Koers, Ninotska I. L. Derksen, Laura Hogenboom, Zoé van Kempen, Joep Killestein, Abraham Rutgers, Peter Heeringa, Barbara Horváth, Taco W. Kuijpers, S. Marieke van Ham, Anja ten Brinke, Diane van der Woude, René E. M. Toes, Nicolaas A. Bos, Theo Rispens, The T2B consortium
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
High Fab glycosylation of autoantibodies maintained during B cell depletion therapy
Changes in Fab glycosylation of total IgG compartment upon B cell depletion therapy in autoantibody-mediated chronic autoimmune diseases
Fab glycosylation autoantibodies
B cell depletion therapy
Chronic autoimmunity
Online Access:https://doi.org/10.1038/s41598-025-99226-y
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Summary:Abstract 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.
ISSN:2045-2322

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