Jj. Yang et al., Target antigens for anti-neutrophil cytoplasmic autoantibodies (ANCA) are on the surface of primed and apoptotic but not unstimulated neutrophils, CLIN EXP IM, 121(1), 2000, pp. 165-172
The reaction of ANCA with ANCA antigens on the surface of neutrophils may p
lay a critical role in the pathogenesis of ANCA vasculitis. Therefore, an u
nderstanding of the circumstances that result in surface expression of thes
e antigens is important for an understanding of pathogenic mechanisms. In t
his study we investigated the surface expression of ANCA antigens on quiesc
ent, primed, and apoptotic neutrophils. ANCA antigens and other granule con
stituents were not detected on the surface of neutrophils in freshly hepari
nized 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 apop
tosis. After 24 h incubation, about 30% of the neutrophils were apoptotic,
and ANCA antigens and other granule constituents were present on the surfac
e of both apoptotic and non-apoptotic cells. Our data indicate that there a
re 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 t
hese observations, we hypothesize that ANCA can react in vivo with primed b
ut not quiescent neutrophils. Previously published observations indicate th
at the interaction of ANCA with primed neutrophils results in neutrophil ac
tivation, which may be involved in the pathogenesis of ANCA vasculitis.