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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)
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Submitter: 石津 明洋
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