In:
Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 7 ( 1999-07), p. 1506-1515
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-α-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 β-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.
Type of Medium:
Online Resource
ISSN:
1046-6673
DOI:
10.1681/ASN.V1071506
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1999
detail.hit.zdb_id:
2029124-3
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