The role of autoantibody as pathogenesis of ideopatic nephrotic syndrome in children
Project/Area Number |
18K07887
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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Research Institution | Teikyo University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
高里 実 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (40788676)
三牧 正和 帝京大学, 医学部, 教授 (40392419)
磯島 豪 帝京大学, 医学部, 講師 (00568230)
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
Keywords | 小児 / 特発性ネフローゼ症候群 / 自己抗体 / ネフローゼ症候群 / 小児腎臓病 / オルガノイド |
Outline of Final Research Achievements |
Idiopathic nephrotic syndrome (NS) is a chronic disease that causes severe proteinuria. The aim of this study was to elucidate the pathogenesis of pediatric idiopathic NS by focusing on autoantibodies in the blood of pediatric patients with NS. Our results showed that (1) the autoantibodies in patients' serum were different from anti-IL-4 antibodies predicted before the study began, (2) autoantibodies bind to molecules on renal epithelial cells, which play an important role in the mechanism that prevents protein leakage into the urine, and (3) in vivo experiments using kidney-derived cell lines showed that patient plasma activates pathways required for maintenance of the renal epithelial cell cytoskeleton. These findings suggest that IgM-class autoantibodies in patient plasma may be involved in the pathogenesis of NS.
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Academic Significance and Societal Importance of the Research Achievements |
特発性NSはその約40%が頻回再発型NSで、ステロイドを長期間にわたって使用するため、成長障害といったステロイドによる小児特有の副作用が問題となっており、患者のQOL低下とあいまって、その発症の原因解明が待たれてきた。 今回の研究では、NSを発症させる物質を同定するには至らなかったものの、IgMクラスの抗体である可能性を示せたことで、例えば血中自己抗体をモニターして疾患の再発を予測するなど、臨床応用する可能性を示すことができたと考えている。
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Report
(5 results)
Research Products
(73 results)
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[Journal Article] Early clinical signs and treatment of Menkes disease.2022
Author(s)
Fujisawa C, Kodama H, Sato Y, Mimaki M, Yagi M, Awano H, Matsuo M, Shintaku H, Yoshida S, Takayanagi M, Kubota M, Takahashi A, Akasaka Y.
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[Journal Article] Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease.2021
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Yamagishi Y, Kudo T, Oyumi M, Sakamoto Y, Takahashi K, Akashi T, Kobayashi S, Kawakami T, Goda H, Sato Y, Mimaki M, Kodama H, Munakata M, Makino K, Takahashi H, Fukami T, Ito K.
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Pharm Res.
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[Journal Article] Rapid progression to end-stage renal disease in a child with IgA-dominant infection-related glomerulonephritis associated with parvovirus B19.2020
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Yoko Shirai, Kenichiro Miura, Tomoo Yabuuchi, Takeshi Nagasawa, Kiyonobu Ishizuka, Kazuhiro Takahashi, Sekiko Taneda, Kazuho Honda, Yutaka Yamaguchi, Hitoshi Suzuki, Yusuke Suzuki, Motoshi Hattori
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Nat Commun .
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[Journal Article] COX6A2 Variants Cause a Muscle-Specific Cytochrome C Oxidase Deficiency2019
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Annals of Neurology
Volume: 86
Issue: 2
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Tran Huu Dat, Ryuichi Sugamata, Tomoyasu Hirose, Shoichi Suzuki, Yoshihiko Noguchi, Akihiro Sugawara, Fuyu Ito, Tomoko Yamamoto, Shoji Kawachi, Kiyoko S. Akagawa, Satoshi Omura, Toshiaki Sunazuka, Naoki Ito, Masakazu Mimaki, Kazuo Suzuki
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Journal Title
J. Antibiot.
Volume: 72
Issue: 10
Pages: 759-768
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[Journal Article] Impact of the Great East Japan Earthquake on Body Mass Index, Weight, and Height of Infants and Toddlers: An Infant Survey2018
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Journal Title
Journal of Epidemiology
Volume: 28
Issue: 5
Pages: 237-244
DOI
NAID
ISSN
0917-5040, 1349-9092
Year and Date
2018-05-05
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[Journal Article] Early excessive growth with distinct seasonality in preschool obesity2018
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Archives of Disease in Childhood
Volume: 104
Issue: 1
Pages: 53-57
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[Presentation] 高度蛋白尿と腎機能障害が遷延したParvovirus B19による感染関連腎炎の1例2018
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第48回日本腎臓学会東部学術総会
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