@article{Kraaij:2018:10.1016/j.kint.2018.01.013,
author = {Kraaij, T and Kamerling, SWA and van, Dam LS and Bakker, JA and Bajema, IM and Page, T and Brunini, F and Pusey, CD and Toes, REM and Scherer, HU and Rabelink, TJ and van, Kooten C and Teng, YKO},
doi = {10.1016/j.kint.2018.01.013},
journal = {Kidney International},
pages = {139--149},
title = {Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA},
url = {http://dx.doi.org/10.1016/j.kint.2018.01.013},
volume = {94},
year = {2018}
}

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TY  - JOUR
AB  - Neutrophil extracellular traps (NETs) are auto-antigenic strands of extracellular DNA covered with myeloperoxidase (MPO) and proteinase3 (PR3) that can be a source for the formation of anti-neutrophil cytoplasmic autoantibodies (ANCAs). The presence of NETs was recently demonstrated in renal tissue of patients with ANCA-associated vasculitis (AAV). NET formation was enhanced in AAV, suggesting that MPO-ANCA could trigger NET formation, supporting a vicious circle placing NETs in the center of AAV pathogenesis. Here we investigated NET formation in 99 patients with AAV by a novel highly sensitive and automated assay. There was a significant excess of ex vivo NET formation in both MPO-ANCA- and PR3-ANCA-positive patients with AAV compared to healthy individuals. Excessive NET formation did not correlate with serum ANCA levels. Likewise, immunoglobulin G depletion had no effect on excessive NET formation in patients with AAV, indicating an ANCA-independent process. Next, we explored the relation of excessive NET formation to clinical disease in ten patients with AAV and showed that excessive NET formation was predominantly found during active disease, more so than during remission. Excessive NET formation was found in patients with AAV hospitalized for disease relapse but not during severe infection. Thus, excessive NET formation in AAV is independent of ANCA, and an excess of ex vivo NET formation was related to active clinical disease in patients with AAV and a marker of autoimmunity rather than infection.
AU  - Kraaij,T
AU  - Kamerling,SWA
AU  - van,Dam LS
AU  - Bakker,JA
AU  - Bajema,IM
AU  - Page,T
AU  - Brunini,F
AU  - Pusey,CD
AU  - Toes,REM
AU  - Scherer,HU
AU  - Rabelink,TJ
AU  - van,Kooten C
AU  - Teng,YKO
DO  - 10.1016/j.kint.2018.01.013
EP  - 149
PY  - 2018///
SN  - 0085-2538
SP  - 139
TI  - Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA
T2  - Kidney International
UR  - http://dx.doi.org/10.1016/j.kint.2018.01.013
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29606398
UR  - http://hdl.handle.net/10044/1/58283
VL  - 94
ER  - 

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