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Neutrophil Extracellular Traps May Contribute to the Pathogenesis in Adult-onset Still Disease

Authors
Ahn, MH | Han, JH  | Chwae, YJ  | Jung, JY  | Suh, CH  | Kwon, JE  | Kim, HA
Citation
The Journal of rheumatology, 46(12). : 1560-1569, 2019
Journal Title
The Journal of rheumatology
ISSN
0315-162X
Abstract
OBJECTIVE: Release of neutrophil extracellular traps (NET) has been described as an effector mechanism of polymorphonuclear neutrophils in several inflammatory diseases. Thus, this study was performed to evaluate the role of NET in the pathogenesis of adult-onset Still disease (AOSD).
METHODS: We determined the serum levels of NET molecules and investigated their associations with clinical disease activities in patients with AOSD. Further, we analyzed the differences in the NETosis response in AOSD patients compared to healthy controls (HC). To explore the in vivo involvement of NET in AOSD, we performed immunohistochemical analysis of skin and lymph node (LN) biopsies for proteins related to NET in patients with active AOSD.
RESULTS: Serum levels of cell-free DNA, myeloperoxidase (MPO)-DNA complex, and alpha-defensin were significantly increased in patients with AOSD compared to HC. Serum levels of the NET molecules, cell-free DNA, MPO-DNA, and alpha-defensin were correlated with several disease activity markers for AOSD. In followup of patients with AOSD after treatment with corticosteroid, the levels of cell-free DNA and alpha-defensin decreased significantly. On immunohistochemistry, neutrophil elastase-positive and MPO-positive inflammatory cells were detected in skin and LN of patients with AOSD, and were expressed in fiber form in the lesions. The serum from patients with active AOSD induced NETosis in neutrophils from HC. NET molecules induced interleukin 1beta production in monocytes, representing a novel mechanism in the pathogenesis of AOSD.
CONCLUSION: The findings presented here suggest that NET may contribute to the inflammatory response and pathogenesis in AOSD.
Keywords
MeSH

DOI
10.3899/jrheum.181058
PMID
31043551
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Rheumatology
Ajou Authors
권, 지은  |  김, 현아  |  서, 창희  |  정, 주양  |  최, 용준  |  한, 재호
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