RT Journal Article
SR Electronic
T1 Neutrophil Extracellular Traps May Contribute to the Pathogenesis in Adult-onset Still Disease
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1560
OP 1569
DO 10.3899/jrheum.181058
VO 46
IS 12
A1 Mi-Hyun Ahn
A1 Jae Ho Han
A1 Young-Jun Chwae
A1 Ju-Yang Jung
A1 Chang-Hee Suh
A1 Ji Eun Kwon
A1 Hyoun-Ah Kim
YR 2019
UL http://www.jrheum.org/content/46/12/1560.abstract
AB 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 α-defensin were significantly increased in patients with AOSD compared to HC. Serum levels of the NET molecules, cell-free DNA, MPO-DNA, and α-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 α-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 1β 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.