Differences in IgG autoantibody Fab glycosylation across autoimmune diseases

Jana Koers; Rocco Sciarrillo; 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; T2B Consortium

doi:10.1016/j.jaci.2022.10.035

Differences in IgG autoantibody Fab glycosylation across autoimmune diseases

J Allergy Clin Immunol. 2023 Jun;151(6):1646-1654. doi: 10.1016/j.jaci.2022.10.035. Epub 2023 Jan 27.

Authors

Jana Koers¹, Rocco Sciarrillo¹, Ninotska I L Derksen¹, Esther M Vletter², Yvonne E Fillié-Grijpma³, Elisabeth Raveling-Eelsing⁴, Nuno A G Graça⁵, Thiemo Leijser¹, Hendri H Pas⁶, L Laura van Nijen-Vos⁶, Maaike V J Braham⁷, Anne-Marie Buisman⁷, Jan de Jong⁸, Angela I Schriek⁹, Anne P Tio-Gillen¹⁰, Y K Onno Teng¹¹, Maurice Steenhuis¹, Francis H Swaneveld¹², Steven W de Taeye⁹, Marit J van Gils⁹, Jan J G M Verschuuren¹³, Bram Rutgers⁴, Peter Heeringa¹⁴, Barbara Horváth⁶, Bart C Jacobs¹⁰, Karina de Leeuw⁴, Casper F M Franssen¹⁵, Agnès Veyradier¹⁶, Paul Coppo¹⁷, Kyra A Gelderman⁸, S Marieke van Ham¹⁸, Cécile A C M van Els¹⁹, Diane van der Woude², Ruth Huizinga⁹, Maartje G Huijbers³, Taco W Kuijpers²⁰, Rene E M Toes², Nicolaas A Bos⁴, Theo Rispens²¹; T2B Consortium

Affiliations

¹ Department of Immunopathology, Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
² Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
³ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Rheumatology and Clinical Immunology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
⁵ Department of Molecular Hematology, Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁶ Centre for Blistering Diseases, Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
⁸ Sanquin Diagnostic Services, Amsterdam, The Netherlands.
⁹ Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.
¹⁰ Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹¹ Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
¹² Department of Transfusion Medicine, Sanquin Blood Bank, Amsterdam, The Netherlands.
¹³ Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁴ Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
¹⁵ Department of Internal Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
¹⁶ Service d'Hématologie biologique, Hôpital Lariboisière and EA-3518 Institut de Recherche Saint Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, France; Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.
¹⁷ Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France; Service d'Hématologie, Hôpital Saint-Antoine, AP-HP, Paris, France; Faculté de médecine, Sorbonne Université, UPMC Univ Paris, Paris, France.
¹⁸ Department of Immunopathology, Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
¹⁹ Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
²⁰ Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands; Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
²¹ Department of Immunopathology, Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: t.rispens@sanquin.nl.

PMID: 36716825
DOI: 10.1016/j.jaci.2022.10.035

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.

Keywords: Autoimmune diseases; Fab glycosylation; IgG; autoantibodies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid*
Autoantibodies
Autoantigens
Autoimmune Diseases*
Humans
Immunoglobulin G
Lupus Erythematosus, Systemic*
Myasthenia Gravis*

Substances

Autoantibodies
Immunoglobulin G
Autoantigens