IgG Glycan Hydrolysis Attenuates ANCA-Mediated Glomerulonephritis
| Autor: | Mattias Collin, Arjen H. Petersen, Coen A. Stegeman, Mirjan M. van Timmeren, Betty S. van der Veen, Peter Heeringa, Thomas Hellmark |
|---|---|
| Přispěvatelé: | Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Male Time Factors Neutrophils STREPTOCOCCUS-PYOGENES Fc receptor urologic and male genital diseases Immunoglobulin G Mice Glomerulonephritis Proteinase 3 ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES Mice Knockout biology Chemistry Hydrolysis HUMAN NEUTROPHILS MYELOPEROXIDASE General Medicine Middle Aged Nephrology Myeloperoxidase Female CRESCENTIC GLOMERULONEPHRITIS INTERACTIONS IN-VIVO Systemic vasculitis Adult Glycoside Hydrolases FC SYSTEMIC VASCULITIS Antibodies Antineutrophil Cytoplasmic Bacterial Proteins Polysaccharides medicine Animals Humans cardiovascular diseases Anti-neutrophil cytoplasmic antibody Aged Peroxidase Autoantibody medicine.disease Mice Inbred C57BL Disease Models Animal Basic Research Case-Control Studies Immunology ANTIBODIES biology.protein WEGENERS GRANULOMATOSIS |
| Zdroj: | Journal of the American Society of Nephrology, 21(7), 1103-1114. AMER SOC NEPHROLOGY |
| ISSN: | 1533-3450 1046-6673 |
| Popis: | Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (Pr3) are considered pathogenic in ANCA-associated necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. Modulation of ANCA IgG glycosylation may potentially reduce its pathogenicity by abolishing Fc receptor mediated activation of leukocytes and complement Here, we investigated whether IgG hydrolysis by the bacterial enzyme endoglycosidase S (EndoS) attenuates ANCA-mediated NCGN. In vitro, treatment of ANCA IgG with EndoS significantly attenuated ANCA-mediated neutrophil activation without affecting antigen-binding capacity. In a mouse model of antiMPO IgG/LPS-induced NCGN, we induced disease with either unmodified or EndoS-treated (deglycosylated) anti-MPO IgG. In separate experiments, we administered EndoS systemically after disease induction with unmodified anti-MPO IgG. Pretreatment of anti-MPO IgG with EndoS reduced hematuria, leukocyturia, and albuminuria and attenuated both neutrophil influx and formation of glomerular crescents After inducing disease with unmodified anti-MPO IgG, systemic treatment with EndoS reduced albuminuria and glomerular crescent formation when initiated after 3 but not 24 hours. In conclusion, IgG glycan hydrolysis by EndoS attenuates ANCA-induced neutrophil activation in vitro and prevents induction of anti-MPO IgG/LPS-mediated NCGN m vivo. Systemic treatment with EndoS early after disease induction attenuates the development of disease. Thus, modulation of IgG glycosylation is a promising strategy to interfere with ANCA-mediated inflammatory processes. |
| Databáze: | OpenAIRE |
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