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IgA腎症における扁桃細菌叢に対する異常粘膜免疫応答
http://hdl.handle.net/10191/0002000303
http://hdl.handle.net/10191/00020003034c3d4d06-86c6-41ee-88cc-4f64113c2662
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本文 (7.02MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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公開日 | 2022-04-04 | |||||||||
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タイトル | Aberrant mucosal immunoreaction to tonsillar microbiota in immunoglobulin A nephropathy | |||||||||
言語 | en | |||||||||
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タイトル | IgA腎症における扁桃細菌叢に対する異常粘膜免疫応答 | |||||||||
言語 | ja | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
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言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | APRIL | |||||||||
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言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | IgA nephropathy | |||||||||
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言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | immunoglobulin repertoire sequencing | |||||||||
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言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | microbiome | |||||||||
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言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | tonsillectomy | |||||||||
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資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
資源タイプ | doctoral thesis | |||||||||
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アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
著者 |
山口, 浩毅
× 山口, 浩毅
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内容記述タイプ | Abstract | |||||||||
内容記述 | Background. Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. Methods. Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gelfiltration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. Results. Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3–30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. Conclusions. These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology. | |||||||||
言語 | en | |||||||||
内容記述 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | Nephrology Dialysis Transplantation. 2021, 36(1), 75–86. | |||||||||
言語 | en | |||||||||
DOI | ||||||||||
識別子タイプ | DOI | |||||||||
関連識別子 | https://doi.org/10.1093/ndt/gfaa223 | |||||||||
権利 | ||||||||||
言語 | en | |||||||||
権利情報 | 【○!C】 The Author(s) 2020. | |||||||||
権利 | ||||||||||
言語 | en | |||||||||
権利情報Resource | https://creativecommons.org/licenses/by-nc/4.0/ | |||||||||
権利情報 | Creative Commons Attribution-NonCommercial 4.0 International | |||||||||
学位名 | ||||||||||
言語 | ja | |||||||||
学位名 | 博士(医学) | |||||||||
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学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関識別子 | 13101 | |||||||||
言語 | ja | |||||||||
学位授与機関名 | 新潟大学 | |||||||||
言語 | en | |||||||||
学位授与機関名 | Niigata University | |||||||||
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学位授与年月日 | 2021-03-23 | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 甲第4844号 | |||||||||
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内容記述タイプ | Other | |||||||||
内容記述 | 新大院博(医)第998号 | |||||||||
言語 | ja |