TY - JOUR
T1 - Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy
AU - Valk, Anika M.
AU - Koers, Jana
AU - The T2B consortium
AU - Derksen, Ninotska I.L.
AU - Hogenboom, Laura
AU - van Kempen, Zoé
AU - Killestein, Joep
AU - Rutgers, Abraham
AU - Heeringa, Peter
AU - Horváth, Barbara
AU - Kuijpers, Taco W.
AU - van Ham, S. Marieke
AU - Brinke, Anja ten
AU - van der Woude, Diane
AU - Toes, René E.M.
AU - Bos, Nicolaas A.
AU - Rispens, Theo
AU - Bos, Amelie
AU - Kummer, Laura Y.
AU - Wieske, Luuk
AU - Koning, Marvyn
AU - van Schouwenburg, Pauline A.
AU - van Binnendijk, Rob
AU - Buisman, Anne Marie
AU - Corneth, Odilia B.J.
AU - Ysermans, Renée
AU - Paardekooper, Laurent M.
AU - van Dam, Koos
AU - Elias, George
AU - Pollastro, Sabrina
AU - Sciarillo, Rocco
AU - Marsman, Casper
AU - Verstegen, Niels
AU - Raveling-Eelsing, Elisabeth
AU - Bonasia, Carlo
AU - Busch, Matthias
AU - Braham, Maaike
AU - Vletter, Esther M.
AU - van der Burg, Mirjam
AU - Desai, Jyaysi
AU - Verhoeven, Dorit
AU - Coppola, Mariateresa
AU - Kielbassa, Karoline
AU - van der Weele, Linda
AU - Ruiter, Annabel M.
AU - Abdulahad, Wayel
AU - Huizinga, Ruth
AU - Hendriks, Rudi W.
AU - Titulaer, Maarten J.
AU - Kater, Arnon
AU - Jacobs, Bart
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/4/28
Y1 - 2025/4/28
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105004336741
U2 - 10.1038/s41598-025-99226-y
DO - 10.1038/s41598-025-99226-y
M3 - Article
C2 - 40295683
AN - SCOPUS:105004336741
SN - 2045-2322
VL - 15
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 14770
ER -