IgG glycan hydrolysis attenuates ANCA-mediated glomerulonephritis.
J Am Soc Nephrol
; 21(7): 1103-14, 2010 Jul.
Article
de En
| MEDLINE
| ID: mdl-20448018
ABSTRACT
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 anti-MPO 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 in 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Polyosides
/
Immunoglobuline G
/
Anticorps anti-cytoplasme des polynucléaires neutrophiles
/
Glomérulonéphrite
Type d'étude:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
J Am Soc Nephrol
Sujet du journal:
NEFROLOGIA
Année:
2010
Type de document:
Article
Pays d'affiliation:
Pays-Bas