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2014 ; 176
(3
): 363-72
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Neutrophils from vasculitis patients exhibit an increased propensity for
activation by anti-neutrophil cytoplasmic antibodies
#MMPMID24666336
Ohlsson SM
; Ohlsson S
; Söderberg D
; Gunnarsson L
; Pettersson Å
; Segelmark M
; Hellmark T
Clin Exp Immunol
2014[Jun]; 176
(3
): 363-72
PMID24666336
show ga
Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in
ANCA-associated vasculitis (AAV) by stimulating polymorphonuclear leucocytes
(PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this
study was to investigate if PMNs from AAV patients are stimulated more readily by
ANCA compared with PMNs from healthy controls (HCs). Differences in ANCA
characteristics that can account for different stimulation potential were also
studied. PMNs from five AAV patients and five HCs were stimulated with 10
different immunoglobulins (Ig)Gs, purified from PR3-ANCA-positive patients, and
ROS production, degranulation and neutrophil extracellular trap (NET) formation
was measured. ANCA levels, affinity and clinical data of the AAV donors were
recorded. The results show that PMNs from AAV patients produce more intracellular
ROS (P?=?0·019), but degranulate to a similar extent as PMNs from HCs. ROS
production correlated with NET formation. Factors that may influence the ability
of ANCA to activate PMNs include affinity and specificity for N-terminal
epitopes. In conclusion, our results indicate that PMNs from AAV patients in
remission behave quite similarly to HC PMNs, with the exception of a greater
intracellular ROS production. This could contribute to more extensive NET
formation and thus an increased exposure of the ANCA autoantigens to the immune
system.