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Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies.

Ohlsson, Susanne LU ; Ohlsson, Sophie LU ; Söderberg, Daniel; Gunnarsson, Lena LU ; Pettersson, Åsa LU ; Segelmark, Mårten LU and Hellmark, Thomas LU (2014) In Clinical and Experimental Immunology 176(3). p.363-372
Abstract
Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in ANCA associated vasculitis (AAV) by stimulating polymorphonuclear leukocytes (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this study was to investigate if PMNs from AAV patients are more readily stimulated 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 5 AAV patients and 5 HCs were stimulated with 10 different IgGs, 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... (More)
Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in ANCA associated vasculitis (AAV) by stimulating polymorphonuclear leukocytes (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this study was to investigate if PMNs from AAV patients are more readily stimulated 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 5 AAV patients and 5 HCs were stimulated with 10 different IgGs, 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 similar 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Immunology
volume
176
issue
3
pages
363 - 372
publisher
British Society for Immunology
external identifiers
  • pmid:24666336
  • wos:000337516700008
  • scopus:84899092051
ISSN
0009-9104
DOI
10.1111/cei.12301
language
English
LU publication?
yes
id
7ef541a7-79a1-4faf-802e-cb50b16a5f2f (old id 4379740)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24666336?dopt=Abstract
date added to LUP
2014-04-03 21:52:50
date last changed
2017-11-19 03:22:30
@article{7ef541a7-79a1-4faf-802e-cb50b16a5f2f,
  abstract     = {Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in ANCA associated vasculitis (AAV) by stimulating polymorphonuclear leukocytes (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this study was to investigate if PMNs from AAV patients are more readily stimulated 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 5 AAV patients and 5 HCs were stimulated with 10 different IgGs, 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 similar 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.},
  author       = {Ohlsson, Susanne and Ohlsson, Sophie and Söderberg, Daniel and Gunnarsson, Lena and Pettersson, Åsa and Segelmark, Mårten and Hellmark, Thomas},
  issn         = {0009-9104},
  language     = {eng},
  number       = {3},
  pages        = {363--372},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies.},
  url          = {http://dx.doi.org/10.1111/cei.12301},
  volume       = {176},
  year         = {2014},
}