TY - JOUR
T1 - Differences in IgG autoantibody Fab glycosylation across autoimmune diseases
AU - T2B consortium
AU - Koers, Jana
AU - Sciarrillo, Rocco
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 - van Nijen-Vos, L Laura
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 - van Ham, S Marieke
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 - Copyright © 2023. Published by Elsevier Inc.
PY - 2023/6
Y1 - 2023/6
N2 - BACKGROUND: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases.OBJECTIVE: To study if elevated Fab glycosylation is a common feature of autoimmunity, we 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, ANCA-associated vasculitis, systemic lupus erythematosus, anti-GBM 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 six out of ten autoantibody responses, in five out of eight diseases, we found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in RA to 26% in SLE. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but 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, we determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to gp120 in chronically HIV-1-infected individuals. 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.CONCLUSION: Our 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.OBJECTIVE: To study if elevated Fab glycosylation is a common feature of autoimmunity, we 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, ANCA-associated vasculitis, systemic lupus erythematosus, anti-GBM 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 six out of ten autoantibody responses, in five out of eight diseases, we found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in RA to 26% in SLE. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but 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, we determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to gp120 in chronically HIV-1-infected individuals. 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.CONCLUSION: Our data indicate that in chronic but not acute B cell-mediated autoimmune diseases disease-specific autoantibodies are enriched for Fab glycans.
U2 - 10.1016/j.jaci.2022.10.035
DO - 10.1016/j.jaci.2022.10.035
M3 - Article
C2 - 36716825
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 -