Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission
2015 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, no 11, 2085-2094 p.Article in journal (Refereed) PublishedText
Objectives. Neutrophil extracellular traps (NETs) have been visualized at the site of ANCA-associated vasculitis (AAV) lesions. Increased levels of NET remnants in the circulation have been reported in some AAV patients with active disease. The aim of the present study was to analyse NET remnants in a larger cohort of AAV patients with varying degrees of disease activity and to elucidate possible factors responsible for remnant variation. Methods. Levels of NET remnants in the circulation of healthy controls (HCs; n =31) and AAV patients (n =93) were determined with ELISA. NET remnants were then correlated with ANCA levels, spontaneous and induced cell death (NETosis/necrosis) in vitro, neutrophil count and corticosteroid therapy. Results. Patients with active disease showed higher levels of circulating NET remnants compared with patients in remission (P=0.026) and HCs (P=0.006). From patients sampled during both remission and active disease, we found increased levels during active disease (P=0.0010). In remission, ANCA-negative patients had higher levels of NET remnants than ANCA-positive patients and a negative correlation was observed between NET remnants and PR3-ANCA (rs = 0.287, P=0.048). NET remnants correlated with neutrophil count in HCs (rs =0.503, P=0.014) but not in patients during remission. Neutrophils from patients showed enhanced spontaneous cell death (P=0.043). Conclusion. We found increased levels of circulating NET remnants in patients with active AAV. Furthermore, AAV patients exhibited an increased propensity for spontaneous cell death. NET remnant levels seem to be positively related to disease activity and neutrophil count, but inversely related to ANCA at least during remission.
Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2015. Vol. 54, no 11, 2085-2094 p.
small vessel vasculitis; ANCA-associated vasculitis; neutrophil extracellular trap (NET); NET remnants; ANCA
IdentifiersURN: urn:nbn:se:liu:diva-123334DOI: 10.1093/rheumatology/kev217ISI: 000364760700023PubMedID: 26170375OAI: oai:DiVA.org:liu-123334DiVA: diva2:882171