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The Presence of Anti-Lactoferrin Antibodies in a Subgroup of Eosinophilic Granulomatosis with Polyangiitis Patients and Their Possible Contribution to Enhancement of Neutrophil Extracellular Trap Formation

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Title: The Presence of Anti-Lactoferrin Antibodies in a Subgroup of Eosinophilic Granulomatosis with Polyangiitis Patients and Their Possible Contribution to Enhancement of Neutrophil Extracellular Trap Formation
Authors: Shida, Haruki Browse this author
Nakazawa, Daigo Browse this author
Tateyama, Yu Browse this author
Miyoshi, Arina Browse this author
Kusunoki, Yoshihiro Browse this author
Hattanda, Fumihiko Browse this author
Masuda, Sakiko Browse this author
Tomaru, Utano Browse this author →KAKEN DB
Kawakami, Tamihiro Browse this author
Atsumi, Tatsuya Browse this author →KAKEN DB
Ishizu, Akihiro Browse this author →KAKEN DB
Keywords: lactoferrin
anti-lactoferrin antibody
neutrophil
neutrophil extracellular trap
eosinophilic granulomatosis with polyangiitis
Issue Date: 23-Dec-2016
Publisher: Frontiers
Journal Title: Frontiers in Immunology
Volume: 7
Start Page: 636
Publisher DOI: 10.3389/fimmu.2016.00636
PMID: 28066444
Abstract: Lactoferrin (Lf) is one of the antigens of antineutrophil cytoplasmic antibodies (ANCA) and functions as an endogenous suppressor of neutrophil extracellular trap (NET) formation. However, the prevalence and pathogenicity of anti-lactoferrin antibodies (aLf) in ANCA-associated vasculitis (AAV) remain unrevealed. This study aimed to examine the significance of aLf in AAV, initially. Sixty-five sera from AAV patients, including 41 microscopic polyangiitis, 5 granulomatosis with polyangiitis, and 19 eosinophilic granulomatosis with polyangiitis (EGPA) patients, were subjected to aLf detection using enzyme-linked immunosorbent assay. Clinical characteristics were compared between aLf-positive and aLf-negative patients. Neutrophils from healthy donors were exposed to suboptimal dose (10 nM) of phorbol myristate acetate (PMA) with aLf followed by evaluation of NET formation. Results demonstrated that 4 out of 65 AAV sera (6.2%) were positive for aLf. All of them were EGPA sera (4/19, 21.1%). In EGPA, the frequency of renal involvement, serum CRP levels, and Birmingham Vasculitis Activity Score (BVAS) in the aLf-positive patients was significantly higher than those in the aLf-negative patients, and the aLf titer correlated positively with the serum CRP level and BVAS. The NET formation was particularly enhanced by combined stimulation of 10 nM PMA and 1 µg/mL aLf. IgG isolated from sera of the aLf-positive EGPA patients (250 µg/mL) enhanced NET formation induced by 10 nM of PMA, and the effect was abolished completely by absorption of the aLf. This pilot study suggests that aLf enhance NET formation induced by PMA and are associated with disease activity of EGPA.
Rights: © 2016 Shida, Nakazawa, Tateyama, Miyoshi, Kusunoki, Hattanda, Masuda, Tomaru, Kawakami, Atsumi and Ishizu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/64033
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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