In vitro neutrophil activation by antibodies to proteinase 3 and myeloperoxidase from patients with crescentic glomerulonephritis.
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.
Department of Internal Medicine, University Hospital Groningen, The Netherlands. m.j.s.hraler@int.azh.nl
C F
CF
Franssen
M G
MG
Huitema
A C
AC
Muller Kobold
W W
WW
Oost-Kort
P C
PC
Limburg
A
A
Tiebosch
C A
CA
Stegeman
C G
CG
Kallenberg
J W
JW
Tervaert
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000494:pharmacology*; D016022:Case-Control Studies; D015550:Cell Degranulation; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005921:Glomerulonephritis / Q000201:enzymology* / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D009195:Peroxidase / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism; D014657:Vasculitis / Q000276:immunology / Q000503:physiopathology
D019268:Antibodies, Antineutrophil Cytoplasmic; D005609:Free Radicals; D007074:Immunoglobulin G; D013481:Superoxides; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin