Target antigens for anti-neutrophil cytoplasmic autoantibodies (ANCA) are on the surface of primed and apoptotic but not unstimulated neutrophils.
The reaction of ANCA with ANCA antigens on the surface of neutrophils may play a critical role in the pathogenesis of ANCA vasculitis. Therefore, an understanding of the circumstances that result in surface expression of these antigens is important for an understanding of pathogenic mechanisms. In this study we investigated the surface expression of ANCA antigens on quiescent, primed, and apoptotic neutrophils. ANCA antigens and other granule constituents were not detected on the surface of neutrophils in freshly heparinized blood. ANCA antigens were on the surface of neutrophils primed by in vitro incubation for 4 h and 8 h. These cells did not show evidence of apoptosis. After 24 h incubation, about 30% of the neutrophils were apoptotic, and ANCA antigens and other granule constituents were present on the surface of both apoptotic and non-apoptotic cells. Our data indicate that there are no ANCA antigens on the surface of quiescent neutrophils, but that they are on the surface of primed neutrophils before the cells become apoptotic, and remain on the surface of cells after they become apoptotic. Based on these observations, we hypothesize that ANCA can react in vivo with primed but not quiescent neutrophils. Previously published observations indicate that the interaction of ANCA with primed neutrophils results in neutrophil activation, which may be involved in the pathogenesis of ANCA vasculitis.
Yang
J J
JJ
Departments of Medicine and Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7155, USA. jjyang@med.unc.edu
Tuttle
R H
RH
Hogan
S L
SL
Taylor
J G
JG
Phillips
B D
BD
Falk
R J
RJ
Jennette
J C
JC
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D009504:Neutrophils / Q000276:immunology*; D011817:Rabbits
D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens