In vitro neutrophil activation by antibodies to proteinase 3 and myeloperoxidase from patients with crescentic glomerulonephritis.
J Am Soc Nephrol
; 10(7): 1506-15, 1999 Jul.
Article
en En
| MEDLINE
| ID: mdl-10405206
ABSTRACT
Previously, it was found that patients with necrotizing crescentic glomerulonephritis (NCGN) and anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against proteinase 3 (anti-PR3) had a faster deterioration of renal function and more active renal vasculitic lesions than patients with ANCA directed against myeloperoxidase (anti-MPO). Because ANCA-mediated neutrophil activation is thought to play an important role in the pathophysiology of this form of glomerulonephritis, this study was conducted to determine whether anti-PR3 are capable of inducing a more pronounced activation of neutrophils in vitro than anti-MPO. To test this hypothesis, the release of reactive oxygen radicals, as assessed by ferricytochrome c reduction and by dihydrorhodamine 123 oxidation, and the release of granule constituents from healthy donor neutrophils upon stimulation with IgG fractions were measured from 17 anti-PR3- and 14 anti-MPO-positive patients with active NCGN. Patients with anti-PR3 had a higher renal activity index (P < 0.05) compared with patients with anti-MPO. IgG fractions from anti-PR3-positive patients induced more oxygen radical release from tumor necrosis factor-alpha-primed neutrophils compared with IgG fractions from anti-MPO-positive patients, as assessed by ferricytochrome c reduction (P < 0.05) and dihydrorhodamine 123 oxidation (P < 0.01). In addition, IgG fractions from anti-PR3-positive patients generated more neutrophil degranulation of beta-glucuronidase (P < 0.01) than IgG fractions from anti-MPO-positive patients. In conclusion, IgG fractions from anti-PR3-positive patients with NCGN are more potent activators of the respiratory burst and degranulation in vitro than IgG fractions from anti-MPO-positive patients. These observations may be relevant in view of the clinical differences between anti-PR3- and anti-MPO-positive patients with NCGN.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Serina Endopeptidasas
/
Peroxidasa
/
Anticuerpos Anticitoplasma de Neutrófilos
/
Glomerulonefritis
/
Neutrófilos
Tipo de estudio:
Observational_studies
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Am Soc Nephrol
Asunto de la revista:
NEFROLOGIA
Año:
1999
Tipo del documento:
Article
País de afiliación:
Países Bajos