Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy

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; Amelie Bos; Laura Y. Kummer; Luuk Wieske; Marvyn Koning; Pauline A. van Schouwenburg; Rob van Binnendijk; Anne Marie Buisman; Odilia B.J. Corneth; Renée Ysermans; Laurent M. Paardekooper; Koos van Dam; George Elias; Sabrina Pollastro; Rocco Sciarillo; Casper Marsman; Niels Verstegen; Elisabeth Raveling-Eelsing; Carlo Bonasia; Matthias Busch; Maaike Braham; Esther M. Vletter; Mirjam van der Burg; Jyaysi Desai; Dorit Verhoeven; Mariateresa Coppola; Karoline Kielbassa; Linda van der Weele; Annabel M. Ruiter; Wayel Abdulahad; Jan G.M.C. Damoiseaux; Jelle de Wit; Reina E. Mebius; Ruth Huizinga; Pieter van Paassen; T2B Consortium

doi:10.1038/s41598-025-99226-y

Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy

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^*, Amelie Bos, Laura Y. Kummer, Luuk Wieske, Marvyn KoningPauline A. van Schouwenburg, Rob van Binnendijk, Anne Marie Buisman, Odilia B.J. Corneth, Renée Ysermans, Laurent M. Paardekooper, Koos van Dam, George Elias, Sabrina Pollastro, Rocco Sciarillo, Casper Marsman, Niels Verstegen, Elisabeth Raveling-Eelsing, Carlo Bonasia, Matthias Busch, Maaike Braham, Esther M. Vletter, Mirjam van der Burg, Jyaysi Desai, Dorit Verhoeven, Mariateresa Coppola, Karoline Kielbassa, Linda van der Weele, Annabel M. Ruiter, Wayel Abdulahad, Jan G.M.C. Damoiseaux, Jelle de Wit, Reina E. Mebius, Ruth Huizinga, Pieter van Paassen, T2B Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	14770
Number of pages	10
Journal	Scientific Reports
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41598-025-99226-y
Publication status	Published - 1 Dec 2025

Keywords

B cell depletion therapy
Changes in Fab glycosylation of total IgG compartment upon B cell depletion therapy in autoantibody-mediated chronic autoimmune diseases
Chronic autoimmunity
Fab glycosylation autoantibodies
High Fab glycosylation of autoantibodies maintained during B cell depletion therapy

Access to Document

10.1038/s41598-025-99226-yLicence: CC BY-NC-ND

Cite this

Valk, A. M., Koers, J., Derksen, N. I. L., Hogenboom, L., van Kempen, Z., Killestein, J., Rutgers, A., Heeringa, P., Horváth, B., Kuijpers, T. W., van Ham, S. M., Brinke, A. T., van der Woude, D., Toes, R. E. M., Bos, N. A., Rispens, T., Bos, A., Kummer, L. Y., Wieske, L., ... T2B Consortium (2025). Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy. Scientific Reports, 15(1), Article 14770. https://doi.org/10.1038/s41598-025-99226-y

@article{a5ec2e15657446d286700f5b117f1e11,

title = "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 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.",

keywords = "B cell depletion therapy, Changes in Fab glycosylation of total IgG compartment upon B cell depletion therapy in autoantibody-mediated chronic autoimmune diseases, Chronic autoimmunity, Fab glycosylation autoantibodies, High Fab glycosylation of autoantibodies maintained during B cell depletion therapy",

author = "Valk, {Anika M.} and Jana Koers and Derksen, {Ninotska I.L.} and Laura Hogenboom and {van Kempen}, Zo{\'e} and Joep Killestein and Abraham Rutgers and Peter Heeringa and Barbara Horv{\'a}th and Kuijpers, {Taco W.} and {van Ham}, {S. Marieke} and Brinke, {Anja ten} and {van der Woude}, Diane and Toes, {Ren{\'e} E.M.} and Bos, {Nicolaas A.} and Theo Rispens and Amelie Bos and Kummer, {Laura Y.} and Luuk Wieske and Marvyn Koning and {van Schouwenburg}, {Pauline A.} and {van Binnendijk}, Rob and Buisman, {Anne Marie} and Corneth, {Odilia B.J.} and Ren{\'e}e Ysermans and Paardekooper, {Laurent M.} and {van Dam}, Koos and George Elias and Sabrina Pollastro and Rocco Sciarillo and Casper Marsman and Niels Verstegen and Elisabeth Raveling-Eelsing and Carlo Bonasia and Matthias Busch and Maaike Braham and Vletter, {Esther M.} and {van der Burg}, Mirjam and Jyaysi Desai and Dorit Verhoeven and Mariateresa Coppola and Karoline Kielbassa and {van der Weele}, Linda and Ruiter, {Annabel M.} and Wayel Abdulahad and Damoiseaux, {Jan G.M.C.} and {de Wit}, Jelle and Mebius, {Reina E.} and Ruth Huizinga and {van Paassen}, Pieter and {T2B Consortium}",

note = "Funding Information: This collaboration project is financed by the PPP Allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) under projectnumber LSHM18055-SGF to stimulate public\u2013private partnerships and co-financing by health foundations that are part of the SGF. This study was supported by ReumaNederland. This study was supported by a research grant from the Landsteiner Foundation for Blood Transfusion (Grant1626) to TR. This study was supported by a research grant from the Vasculitis Foundation to PH (2016) ( http://www.vasculitisfoundation.org/research/research-program/ ). Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

day = "1",

doi = "10.1038/s41598-025-99226-y",

language = "English",

volume = "15",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Valk, AM, Koers, J, Derksen, NIL, Hogenboom, L, van Kempen, Z, Killestein, J, Rutgers, A, Heeringa, P, Horváth, B, Kuijpers, TW, van Ham, SM, Brinke, AT, van der Woude, D, Toes, REM, Bos, NA, Rispens, T, Bos, A, Kummer, LY, Wieske, L, Koning, M, van Schouwenburg, PA, van Binnendijk, R, Buisman, AM, Corneth, OBJ, Ysermans, R, Paardekooper, LM, van Dam, K, Elias, G, Pollastro, S, Sciarillo, R, Marsman, C, Verstegen, N, Raveling-Eelsing, E, Bonasia, C, Busch, M, Braham, M, Vletter, EM, van der Burg, M, Desai, J, Verhoeven, D, Coppola, M, Kielbassa, K, van der Weele, L, Ruiter, AM, Abdulahad, W, Damoiseaux, JGMC, de Wit, J, Mebius, RE, Huizinga, R, van Paassen, P & T2B Consortium 2025, 'Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy', Scientific Reports, vol. 15, no. 1, 14770. https://doi.org/10.1038/s41598-025-99226-y

TY - JOUR

T1 - Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy

AU - Valk, Anika M.

AU - Koers, Jana

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 - Damoiseaux, Jan G.M.C.

AU - de Wit, Jelle

AU - Mebius, Reina E.

AU - Huizinga, Ruth

AU - van Paassen, Pieter

AU - T2B Consortium

N1 - Funding Information: This collaboration project is financed by the PPP Allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) under projectnumber LSHM18055-SGF to stimulate public\u2013private partnerships and co-financing by health foundations that are part of the SGF. This study was supported by ReumaNederland. This study was supported by a research grant from the Landsteiner Foundation for Blood Transfusion (Grant1626) to TR. This study was supported by a research grant from the Vasculitis Foundation to PH (2016) ( http://www.vasculitisfoundation.org/research/research-program/ ). Publisher Copyright: © The Author(s) 2025.

PY - 2025/12/1

Y1 - 2025/12/1

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.

KW - B cell depletion therapy

KW - Changes in Fab glycosylation of total IgG compartment upon B cell depletion therapy in autoantibody-mediated chronic autoimmune diseases

KW - Chronic autoimmunity

KW - Fab glycosylation autoantibodies

KW - High Fab glycosylation of autoantibodies maintained during B cell depletion therapy

U2 - 10.1038/s41598-025-99226-y

DO - 10.1038/s41598-025-99226-y

M3 - Article

SN - 2045-2322

VL - 15

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14770

ER -

Elevated Fab glycosylation of autoantibodies maintained during B cell depletion therapy

Abstract

Keywords

Access to Document

Fingerprint

Cite this