Differences in IgG autoantibody Fab glycosylation across autoimmune diseases

Jana Koers; Rocco Sciarrillo; T2B Consortium; Ninotska I.L. Derksen; Esther M. Vletter; Yvonne E. Fillié-Grijpma; Elisabeth Raveling-Eelsing; Nuno A.G. Graça; Thiemo Leijser; Hendri H. Pas; L. Laura van Nijen-Vos; Maaike V.J. Braham; Anne Marie Buisman; Jan de Jong; Angela I. Schriek; Anne P. Tio-Gillen; Y. K.Onno Teng; Maurice Steenhuis; Francis H. Swaneveld; Steven W. de Taeye; Marit J. van Gils; Jan J.G.M. Verschuuren; Bram Rutgers; Peter Heeringa; Barbara Horváth; Bart C. Jacobs; Karina de Leeuw; Casper F.M. Franssen; Agnès Veyradier; Paul Coppo; Kyra A. Gelderman; S. Marieke van Ham; Cécile A.C.M. van Els; Diane van der Woude; Ruth Huizinga; Maartje G. Huijbers; Taco W. Kuijpers; Rene E.M. Toes; Nicolaas A. Bos; Theo Rispens

doi:10.1016/j.jaci.2022.10.035

Differences in IgG autoantibody Fab glycosylation across autoimmune diseases

Jana Koers, Rocco Sciarrillo, T2B Consortium, Ninotska I.L. Derksen, Esther M. Vletter, Yvonne E. Fillié-Grijpma, Elisabeth Raveling-Eelsing, Nuno A.G. Graça, Thiemo Leijser, Hendri H. Pas, L. Laura van Nijen-Vos, Maaike V.J. Braham, Anne Marie Buisman, Jan de Jong, Angela I. Schriek, Anne P. Tio-Gillen, Y. K.Onno Teng, Maurice Steenhuis, Francis H. Swaneveld, Steven W. de TaeyeMarit J. van Gils, Jan J.G.M. Verschuuren, Bram Rutgers, Peter Heeringa, Barbara Horváth, Bart C. Jacobs, Karina de Leeuw, Casper F.M. Franssen, Agnès Veyradier, Paul Coppo, Kyra A. Gelderman, S. Marieke van Ham, Cécile A.C.M. van Els, Diane van der Woude, Ruth Huizinga, Maartje G. Huijbers, Taco W. Kuijpers, Rene E.M. Toes, Nicolaas A. Bos, Theo Rispens^*

^*Corresponding author for this work

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

27 Citations (Scopus)

Abstract

Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objectives: To study whether elevated Fab glycosylation is a common feature of autoimmunity, this study investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell–mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, antineutrophil cytoplasmic antibody–associated vasculitis, systemic lupus erythematosus, anti–glomerular basement membrane glomerulonephritis, thrombotic thrombocytopenic purpura, and Guillain-Barré syndrome. Methods: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays. Results: In 6 of 10 autoantibody responses, in 5 of 8 diseases, the investigators found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in rheumatoid arthritis to 26% in systemic lupus erythematosus. Elevated autoantibody Fab glycosylation was not restricted to IgG₄, which is known to be prone to Fab glycosylation, but was also present in IgG₁. When autoimmune diseases with a chronic disease course were compared with more acute autoimmune illnesses, increased Fab glycosylation was restricted to the chronic diseases. As a proxy for chronic autoantigen exposure, the investigators determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to glycoprotein 120 in individuals who are chronically HIV-1–infected. Immunity to these viral antigens was not associated with increased Fab glycosylation levels, indicating that chronic antigen-stimulation as such does not lead to increased Fab glycosylation levels. Conclusions: These data indicate that in chronic but not acute B cell–mediated autoimmune diseases, disease-specific autoantibodies are enriched for Fab glycans.

Original language	English
Pages (from-to)	1646-1654
Number of pages	9
Journal	Journal of Allergy and Clinical Immunology
Volume	151
Issue number	6
Early online date	27 Jan 2023
DOIs	https://doi.org/10.1016/j.jaci.2022.10.035
Publication status	Published - Jun 2023

Bibliographical note

Funding Information:
This collaboration project is financed by the Public-Private Partnership Allowance made available by Top Sector Life Sciences and Health to Samenwerkende Gezondheidsfondsen (SGF) under project LSHM18055-SGF to stimulate public-private partnerships and cofinancing 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 (grant 1626) to T.R. M.G.H. receives financial support from the Leiden University Medical Center (Gisela Their Fellowship 2021), Top Sector Life Sciences and Health to SGF (projects LSHM18055-SGF and LSHM19130), Prinses Beatrix Spierfonds (W.OR-19.13), and the Dutch Science Organization Nederlandse Organisatie voor Wetenschappelijk Onderzoek (grant VENI 0915016181 0040 ). This study was supported by a research grant from the Vasculitis Foundation to P.H. (2016) ( http://www.vasculitisfoundation.org/research/research-program/ ).

Publisher Copyright:
© 2023 American Academy of Allergy, Asthma & Immunology

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https://hdl.handle.net/1887/3633624Licence: Article 25fa Dutch Copyright Act

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Koers, J., Sciarrillo, R., T2B Consortium, Derksen, N. I. L., Vletter, E. M., Fillié-Grijpma, Y. E., Raveling-Eelsing, E., Graça, N. A. G., Leijser, T., Pas, H. H., Laura van Nijen-Vos, L., Braham, M. V. J., Buisman, A. M., de Jong, J., Schriek, A. I., Tio-Gillen, A. P., Teng, Y. K. O., Steenhuis, M., Swaneveld, F. H., ... Rispens, T. (2023). Differences in IgG autoantibody Fab glycosylation across autoimmune diseases. Journal of Allergy and Clinical Immunology, 151(6), 1646-1654. https://doi.org/10.1016/j.jaci.2022.10.035

@article{d15e706f27ac462f9c395fb136bd37a1,

title = "Differences in IgG autoantibody Fab glycosylation across autoimmune diseases",

abstract = "Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objectives: To study whether elevated Fab glycosylation is a common feature of autoimmunity, this study investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell–mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, antineutrophil cytoplasmic antibody–associated vasculitis, systemic lupus erythematosus, anti–glomerular basement membrane glomerulonephritis, thrombotic thrombocytopenic purpura, and Guillain-Barr{\'e} syndrome. Methods: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays. Results: In 6 of 10 autoantibody responses, in 5 of 8 diseases, the investigators found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in rheumatoid arthritis to 26% in systemic lupus erythematosus. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but was also present in IgG1. When autoimmune diseases with a chronic disease course were compared with more acute autoimmune illnesses, increased Fab glycosylation was restricted to the chronic diseases. As a proxy for chronic autoantigen exposure, the investigators determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to glycoprotein 120 in individuals who are chronically HIV-1–infected. Immunity to these viral antigens was not associated with increased Fab glycosylation levels, indicating that chronic antigen-stimulation as such does not lead to increased Fab glycosylation levels. Conclusions: These data indicate that in chronic but not acute B cell–mediated autoimmune diseases, disease-specific autoantibodies are enriched for Fab glycans.",

author = "Jana Koers and Rocco Sciarrillo and {T2B Consortium} and Derksen, {Ninotska I.L.} and Vletter, {Esther M.} and Filli{\'e}-Grijpma, {Yvonne E.} and Elisabeth Raveling-Eelsing and Gra{\c c}a, {Nuno A.G.} and Thiemo Leijser and Pas, {Hendri H.} and {Laura van Nijen-Vos}, L. and Braham, {Maaike V.J.} and Buisman, {Anne Marie} and {de Jong}, Jan and Schriek, {Angela I.} and Tio-Gillen, {Anne P.} and Teng, {Y. K.Onno} and Maurice Steenhuis and Swaneveld, {Francis H.} and {de Taeye}, {Steven W.} and {van Gils}, {Marit J.} and Verschuuren, {Jan J.G.M.} and Bram Rutgers and Peter Heeringa and Barbara Horv{\'a}th and Jacobs, {Bart C.} and {de Leeuw}, Karina and Franssen, {Casper F.M.} and Agn{\`e}s Veyradier and Paul Coppo and Gelderman, {Kyra A.} and {Marieke van Ham}, S. and {van Els}, {C{\'e}cile A.C.M.} and {van der Woude}, Diane and Ruth Huizinga and Huijbers, {Maartje G.} and Kuijpers, {Taco W.} and Toes, {Rene E.M.} and Bos, {Nicolaas A.} and Theo Rispens",

note = "Funding Information: This collaboration project is financed by the Public-Private Partnership Allowance made available by Top Sector Life Sciences and Health to Samenwerkende Gezondheidsfondsen (SGF) under project LSHM18055-SGF to stimulate public-private partnerships and cofinancing 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 (grant 1626) to T.R. M.G.H. receives financial support from the Leiden University Medical Center (Gisela Their Fellowship 2021), Top Sector Life Sciences and Health to SGF (projects LSHM18055-SGF and LSHM19130), Prinses Beatrix Spierfonds (W.OR-19.13), and the Dutch Science Organization Nederlandse Organisatie voor Wetenschappelijk Onderzoek (grant VENI 0915016181 0040 ). This study was supported by a research grant from the Vasculitis Foundation to P.H. (2016) ( http://www.vasculitisfoundation.org/research/research-program/ ). Publisher Copyright: {\textcopyright} 2023 American Academy of Allergy, Asthma & Immunology",

year = "2023",

month = jun,

doi = "10.1016/j.jaci.2022.10.035",

language = "English",

volume = "151",

pages = "1646--1654",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "6",

}

Koers, J, Sciarrillo, R, T2B Consortium, Derksen, NIL, Vletter, EM, Fillié-Grijpma, YE, Raveling-Eelsing, E, Graça, NAG, Leijser, T, Pas, HH, Laura van Nijen-Vos, L, Braham, MVJ, Buisman, AM, de Jong, J, Schriek, AI, Tio-Gillen, AP, Teng, YKO, Steenhuis, M, Swaneveld, FH, de Taeye, SW, van Gils, MJ, Verschuuren, JJGM, Rutgers, B, Heeringa, P, Horváth, B, Jacobs, BC, de Leeuw, K, Franssen, CFM, Veyradier, A, Coppo, P, Gelderman, KA, Marieke van Ham, S, van Els, CACM, van der Woude, D, Huizinga, R, Huijbers, MG, Kuijpers, TW, Toes, REM, Bos, NA & Rispens, T 2023, 'Differences in IgG autoantibody Fab glycosylation across autoimmune diseases', Journal of Allergy and Clinical Immunology, vol. 151, no. 6, pp. 1646-1654. https://doi.org/10.1016/j.jaci.2022.10.035

TY - JOUR

T1 - Differences in IgG autoantibody Fab glycosylation across autoimmune diseases

AU - Koers, Jana

AU - Sciarrillo, Rocco

AU - T2B Consortium

AU - Derksen, Ninotska I.L.

AU - Vletter, Esther M.

AU - Fillié-Grijpma, Yvonne E.

AU - Raveling-Eelsing, Elisabeth

AU - Graça, Nuno A.G.

AU - Leijser, Thiemo

AU - Pas, Hendri H.

AU - Laura van Nijen-Vos, L.

AU - Braham, Maaike V.J.

AU - Buisman, Anne Marie

AU - de Jong, Jan

AU - Schriek, Angela I.

AU - Tio-Gillen, Anne P.

AU - Teng, Y. K.Onno

AU - Steenhuis, Maurice

AU - Swaneveld, Francis H.

AU - de Taeye, Steven W.

AU - van Gils, Marit J.

AU - Verschuuren, Jan J.G.M.

AU - Rutgers, Bram

AU - Heeringa, Peter

AU - Horváth, Barbara

AU - Jacobs, Bart C.

AU - de Leeuw, Karina

AU - Franssen, Casper F.M.

AU - Veyradier, Agnès

AU - Coppo, Paul

AU - Gelderman, Kyra A.

AU - Marieke van Ham, S.

AU - van Els, Cécile A.C.M.

AU - van der Woude, Diane

AU - Huizinga, Ruth

AU - Huijbers, Maartje G.

AU - Kuijpers, Taco W.

AU - Toes, Rene E.M.

AU - Bos, Nicolaas A.

AU - Rispens, Theo

N1 - Funding Information: This collaboration project is financed by the Public-Private Partnership Allowance made available by Top Sector Life Sciences and Health to Samenwerkende Gezondheidsfondsen (SGF) under project LSHM18055-SGF to stimulate public-private partnerships and cofinancing 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 (grant 1626) to T.R. M.G.H. receives financial support from the Leiden University Medical Center (Gisela Their Fellowship 2021), Top Sector Life Sciences and Health to SGF (projects LSHM18055-SGF and LSHM19130), Prinses Beatrix Spierfonds (W.OR-19.13), and the Dutch Science Organization Nederlandse Organisatie voor Wetenschappelijk Onderzoek (grant VENI 0915016181 0040 ). This study was supported by a research grant from the Vasculitis Foundation to P.H. (2016) ( http://www.vasculitisfoundation.org/research/research-program/ ). Publisher Copyright: © 2023 American Academy of Allergy, Asthma & Immunology

PY - 2023/6

Y1 - 2023/6

N2 - Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objectives: To study whether elevated Fab glycosylation is a common feature of autoimmunity, this study investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell–mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, antineutrophil cytoplasmic antibody–associated vasculitis, systemic lupus erythematosus, anti–glomerular basement membrane glomerulonephritis, thrombotic thrombocytopenic purpura, and Guillain-Barré syndrome. Methods: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays. Results: In 6 of 10 autoantibody responses, in 5 of 8 diseases, the investigators found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in rheumatoid arthritis to 26% in systemic lupus erythematosus. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but was also present in IgG1. When autoimmune diseases with a chronic disease course were compared with more acute autoimmune illnesses, increased Fab glycosylation was restricted to the chronic diseases. As a proxy for chronic autoantigen exposure, the investigators determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to glycoprotein 120 in individuals who are chronically HIV-1–infected. Immunity to these viral antigens was not associated with increased Fab glycosylation levels, indicating that chronic antigen-stimulation as such does not lead to increased Fab glycosylation levels. Conclusions: These data indicate that in chronic but not acute B cell–mediated autoimmune diseases, disease-specific autoantibodies are enriched for Fab glycans.

AB - Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objectives: To study whether elevated Fab glycosylation is a common feature of autoimmunity, this study investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell–mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, antineutrophil cytoplasmic antibody–associated vasculitis, systemic lupus erythematosus, anti–glomerular basement membrane glomerulonephritis, thrombotic thrombocytopenic purpura, and Guillain-Barré syndrome. Methods: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays. Results: In 6 of 10 autoantibody responses, in 5 of 8 diseases, the investigators found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in rheumatoid arthritis to 26% in systemic lupus erythematosus. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but was also present in IgG1. When autoimmune diseases with a chronic disease course were compared with more acute autoimmune illnesses, increased Fab glycosylation was restricted to the chronic diseases. As a proxy for chronic autoantigen exposure, the investigators determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to glycoprotein 120 in individuals who are chronically HIV-1–infected. Immunity to these viral antigens was not associated with increased Fab glycosylation levels, indicating that chronic antigen-stimulation as such does not lead to increased Fab glycosylation levels. Conclusions: These data indicate that in chronic but not acute B cell–mediated autoimmune diseases, disease-specific autoantibodies are enriched for Fab glycans.

UR - http://www.scopus.com/inward/record.url?scp=85148707321&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2022.10.035

DO - 10.1016/j.jaci.2022.10.035

M3 - Article

C2 - 36716825

AN - SCOPUS:85148707321

SN - 0091-6749

VL - 151

SP - 1646

EP - 1654

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 6

ER -

Differences in IgG autoantibody Fab glycosylation across autoimmune diseases

Abstract

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