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Enhanced Formation and Disordered Regulation of NETs in Myeloperoxidase-ANCA-Associated Microscopic Polyangiitis.

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Title: Enhanced Formation and Disordered Regulation of NETs in Myeloperoxidase-ANCA-Associated Microscopic Polyangiitis.
Authors: Nakazawa, Daigo Browse this author
Shida, Haruki Browse this author
Tomaru, Utano Browse this author →KAKEN DB
Yoshida, Masaharu Browse this author
Nishio, Saori Browse this author →KAKEN DB
Atsumi, Tatsuya Browse this author →KAKEN DB
Ishizu, Akihiro Browse this author →KAKEN DB
Keywords: ANCA
Issue Date: 2-Jan-2014
Publisher: American Society of Nephrology
Journal Title: Journal of the American Society of Nephrology : JASN
Publisher DOI: 10.1681/ASN.2013060606
PMID: 24385592
Abstract: Microscopic polyangiitis (MPA) is an ANCA-associated vasculitis that affects small vessels, especially renal glomeruli. We recently demonstrated that the abnormal formation and impaired degradation of neutrophil extracellular traps (NETs) may be crucially involved in the generation of myeloperoxidase (MPO)-ANCA and subsequent development of MPA. This study assessed the formation and regulation of NETs in patients with MPO-ANCA-associated MPA. Peripheral blood samples were obtained from 38 patients with MPO-ANCA-associated MPA, 23 patients with systemic lupus erythematosus (SLE), and 8 healthy controls. IgG eluted from MPO-ANCA-associated MPA sera demonstrated the highest ability to induce NETs, and this ability correlated with disease activity and paralleled ANCA affinity for MPO. Moreover, addition of recombinant human MPO to these IgG samples reduced NET induction. Additionally, MPO-ANCA-associated MPA sera exhibited lower rates of NET degradation that recovered partially upon depletion of IgG. The activity of DNase I, an important regulator of NETs, was also lower in MPO-ANCA-associated MPA and SLE sera. IgG depletion from MPO-ANCA-associated MPA sera partially restored the rate of NET degradation, and addition of DNase I synergistically enhanced this restoration. Addition of anti-MPO antibodies did not inhibit DNase I activity, and some MPO-ANCA-associated MPA sera contained anti-NET antibodies at levels not correlated with MPO-ANCA titers, suggesting the involvement of unidentified autoantibodies as well. The collective evidence suggests a vicious cycle involving MPO-ANCA and the regulation of NETs could be critically involved in the pathogenesis of MPO-ANCA-associated MPA.
Type: article (author version)
Appears in Collections:保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石津 明洋

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