Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile

• Material Type: 博士論文
• Title: Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile
• Author/Editor: Ito, Masayuki
• Publication, Distribution, etc.: 新潟大学
• Publication Date: 2019-03-15
• Publication Date (W3CDTF): 2019-03-15
• Alternative Title: Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile; 高齢発症の遺伝性肺胞蛋白症とそのサイトカインプロファイル
• Degree grantor/type: 新潟大学
• Date Granted: 2019-03-15
• Date Granted (W3CDTF): 2019-03-15
• Dissertation Number: 乙第2230号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 乙第2230号
• Text Language Code: eng
• Subject Heading: Hereditary pulmonary alveolar proteinosis; GM-CSF; GM-CSF receptor; Elderly onset; Cytokine profile
• Note (General): Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP.Case presentation: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage. She tested negative for GM-CSF autoantibodies, with no underlying disease. Her serum GM-CSF level was elevated (91.3 pg/mL), indicating GM-CSF signaling impairment and genetic defects in the GM-CSF receptor. GM-CSF-stimulated phosphorylation in signal transducer and activator of transcription 5 (STAT5) was not observed, and GM-CSF-Rα expression was defective in her blood cells. Genetic screening revealed a homozygous, single-base C > T mutation at nt 508—a nonsense mutation that yields a stop codon (Q170X)—in exon 7 of CSF2RA. High-resolution analysis of single nucleotide polymorphism array confirmed a 22.8-Mb loss of heterozygosity region in Xp22.33p22.11, encompassing the CSF2RA gene. She was successfully treated with whole lung lavage (WLL), which reduced the serum levels of interleukin (IL)-2, IL-5, and IL-17, although IL-3 and M-CSF levels remained high.Conclusions: This is the first known report of elderly-onset hPAP associated with a CSF2RA mutation, which caused defective GM-CSF-Rα expression and impaired signaling. The analyses of serum cytokine levels during WLL suggested that GM-CSF signaling might be compensated by other signaling pathways, leading to elderly-onset PAP.; 学位の種類: 博士（医学）. 報告番号: 乙第2230号. 学位記番号: 新大博（医）乙第1802号. 学位授与年月日: 平成31年3月15日; BMC Pulmonary Medicine. 2017, 17:40; 新大博（医）乙第1802号; 開始ページ : 1; 終了ページ : 7
• DOI: info:doi/10.1186/s12890-017-0382-x; https://doi.org/info:doi/10.1186/s12890-017-0382-x
• Persistent ID (NDL): info:ndljp/pid/11337448; https://dl.ndl.go.jp/pid/11337448
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-08-03T12:23:27+09:00
• Date Created (W3CDTF): 2019-09-10
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10191/51290
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp