Immunoglobulins G from patients with ANCA-associated vasculitis are atypically glycosylated in both the Fc and Fab regions and the relation to disease activity

PloS One
Olivier M LardinoisRonald J Falk

Abstract

Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are pathogenic in ANCA-associated vasculitis (AAV). The respective role of IgG Fc and Fab glycosylation in mediating ANCA pathogenicity is incompletely understood. Herein we investigate in detail the changes in Fc and Fab glycosylation in MPO-ANCA and Pr3-ANCA and examine the association of glycosylation aberrancies with disease activity. Total IgG was isolated from serum or plasma of a cohort of 30 patients with AAV (14 MPO-ANCA; 16 PR3-ANCA), and 19 healthy control subjects. Anti-MPO specific IgG was affinity-purified from plasma of an additional cohort of 18 MPO-ANCA patients undergoing plasmapheresis. We used lectin binding assays, liquid chromatography, and mass spectrometry-based methods to analyze Fc and Fab glycosylation, the degree of sialylation of Fc and Fab fragments and to determine the exact localization of N-glycans on Fc and Fab fragments. IgG1 Fc glycosylation of total IgG was significantly reduced in patients with active AAV compared to controls. Clinical remission was associated with complete glycan normalization for PR3-ANCA patients but not for MPO-ANCA patients. Fc-glycosylation of anti-MPO speci...Continue Reading

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Citations

Jan 11, 2020·Frontiers in Immunology·Milla R McLeanAmy W Chung
Sep 24, 2019·Antibodies·Danlin YangThomas Laue
Aug 29, 2020·Nature Reviews. Disease Primers·A Richard KitchingRenate Kain
Mar 18, 2021·Autoimmunity Reviews·Xing ZhouWeici Zhang
Sep 22, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caleigh Mandel-BrehmKevin C O'Connor
Dec 28, 2021·Journal of Clinical Laboratory Analysis·Wei WangChunfang Gao

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Methods Mentioned

BETA
glycosylation
pull-down
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

novo
GraphPad
GraphPad Prism
PEAKS DB
PEAKS Studio
De
IGBLAST

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