{"created":"2021-03-01T06:38:17.597938+00:00","id":32046,"links":{},"metadata":{"_buckets":{"deposit":"ecc5de72-481b-4572-8530-05278aeb3d99"},"_deposit":{"id":"32046","owners":[],"pid":{"revision_id":0,"type":"depid","value":"32046"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00032046","sets":["453:455","471:561:562"]},"item_6_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"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"}]},"item_6_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-03-15","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"7","bibliographicPageStart":"1","bibliographic_titles":[{}]}]},"item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-03-15"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"新潟大学"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.\nCase 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.\nConclusions: 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.","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"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","subitem_description_type":"Other"},{"subitem_description":"BMC Pulmonary Medicine. 2017, 17:40","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大博（医）乙第1802号","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"13101乙第2230号"}]},"item_6_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"175112","nameIdentifierScheme":"WEKO"}],"names":[{"name":"伊藤, 正行"}]}]},"item_6_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟大学"}]},"item_6_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.1186/s12890-017-0382-x","subitem_relation_type_select":"DOI"}}]},"item_6_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"ETD"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Ito, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"175111","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-09-10"}],"displaytype":"detail","filename":"h30nmo1802.pdf","filesize":[{"value":"1.7 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","url":"https://niigata-u.repo.nii.ac.jp/record/32046/files/h30nmo1802.pdf"},"version_id":"fea3aaa5-fc0b-4f4b-b757-801fae811043"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-09-10"}],"displaytype":"detail","filename":"h30nmo1802_a.pdf","filesize":[{"value":"595.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","url":"https://niigata-u.repo.nii.ac.jp/record/32046/files/h30nmo1802_a.pdf"},"version_id":"01f42b9d-faf2-4816-a5a4-5270027b0604"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Hereditary pulmonary alveolar proteinosis","subitem_subject_scheme":"Other"},{"subitem_subject":"GM-CSF","subitem_subject_scheme":"Other"},{"subitem_subject":"GM-CSF receptor","subitem_subject_scheme":"Other"},{"subitem_subject":"Elderly onset","subitem_subject_scheme":"Other"},{"subitem_subject":"Cytokine profile","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile"},{"subitem_title":"Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile","subitem_title_language":"en"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-07-09"},"publish_date":"2019-07-09","publish_status":"0","recid":"32046","relation_version_is_last":true,"title":["Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile"],"weko_creator_id":"1","weko_shared_id":2},"updated":"2022-12-15T04:02:23.278199+00:00"}