Pulmonary Alveolar Proteinosis (PAP) and Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy--ClinicalFeatures Predicting Response and Recurrence.

肺泡蛋白沉积症 (PAP) 和吸入粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 治疗 - 预测反应和复发的临床特征。

• 批准号: 22590852
• 负责人: TAZAWA Ryushi
• 金额: $ 2.75万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590852/
• 关键词: 肺胞蛋白症; 吸入治療; GM-CSF; 自己抗体; バイオマーカー; 気管支肺胞洗浄; 抗GM-CSF抗体; 肺機能検査; 無治療期間; 肺活量; GM-CSF抗体; 気管支肺胞洗浄液; サーファクタント; AaDO2; 抗体産生; クリアランス

Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. To figure out predictive and prognostic factors for GM-CSF inhalation therapy in aPAP, we performed retrospective analyses of BALF obtained in aPAP patients before and after GM-CSF inhalation therapy. We confirmed that GM-CSF inhalation was associated with a decrease of GM-Ab in the BALF in improved lungs, which was probably due to the restoration of clearance, and that GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleuki-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis. Furthermore, through the post-treatment, 30-month observation, we concluded that inhaled GM-CSF therapy sustained remission in more than half of cases, and baseline %VC might be a prognostic factor for disease recurrence.

自身免疫性肺泡蛋白沉积症（aPAP）是由肺中的粒细胞/巨噬细胞集落刺激因子（GM-CSF）自身抗体引起的。此前，我们报道过GM-CSF吸入治疗可以改善这些患者的肺泡-动脉氧差和疾病严重程度的血清生物标志物。为了找出GM-CSF吸入治疗aPAP的预测和预后因素，我们对GM-CSF吸入治疗前后aPAP患者的BALF进行了回顾性分析。结论：吸入GM-CSF可降低BALF中GM-Ab的含量，这可能与清除率的恢复有关;吸入GM-CSF可降低BALF中总蛋白和SP-A的含量，增加白细胞介素-17和癌抗原-125的含量。此外，通过治疗后30个月的观察，我们得出结论，吸入GM-CSF治疗使一半以上的病例持续缓解，基线%VC可能是疾病复发的预后因素。

项目成果

Pulmonary Alveolar Proteinosis (PAP) And Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy―Clinical Features Predicting Recurrence.

肺泡蛋白沉积症 (PAP) 和吸入粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 治疗——预测复发的临床特征。

• 发表时间: 2012
• 作者: R. Tazawa;T. Arai;T. Takada;Y. Kasahara;Y. Tsuchihashi;T. Nei;M. Hojo;H. Nakayama;M. Yokoba;H. Ishii;R. Eda;Y. Nasuhara;M. Ebina;M. Akira;E. Yamaguchi;Y. Inoue;K. Nakata.
• 通讯作者: K. Nakata.

Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells.

CD4 T 细胞中的 Runx1 缺陷会因细胞自发过度激活而导致致命的自身免疫性炎症性肺病。

• DOI: 10.4049/jimmunol.1102991
• 发表时间: 2012
• 期刊: J Immunol.
• 作者: Wong WF;Tazawa R;（15名略）Nakata K;Takai T;Satake M.
• 通讯作者: Satake M.

Trapnell. A Multicenter, International Evaluation Of Blood Testing For The Diagnosis Of Autoimmune Pulmonary Alveolar Proteinosis

特拉普内尔。

• 发表时间: 2011
• 作者: Brenna Carey;Kanji Uchida;Koh Nakata;Ryushi Tazawa;Yoshikazu Inoue;Masaki Hirose;Mani S. Kavuru;Mary J. Thomassen;Maurizio Luisetti;Francesca Mariani;Ilaria Campo;Ulrich Costabel;Francesco Bonella;Rhonda Vandyke;Claudia Chalk;and Bruce C
• 通讯作者: and Bruce C

IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis.

• DOI: 10.1152/ajplung.00378.2011
• 发表时间: 2012-05
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: T. Nei;S. Urano;N. Motoi;J. Takizawa;C. Kaneko;H. Kanazawa;R. Tazawa;K. Nakagaki;K. Akagawa;K. Akasaka;T. Ichiwata;A. Azuma;K. Nakata

Acell free assay to estimate the neutralizing capacity of granulocyte-macrophage colony-stimulating factor autoantibodies.

无细胞测定法评估粒细胞-巨噬细胞集落刺激因子自身抗体的中和能力。

• 发表时间: 2010
• 期刊: .J Immunol Methods.
• 作者: Urano S;Kaneko C;Nei T;Motoi N;Tazawa R;(4人略)Nakata K.
• 通讯作者: (4人略)Nakata K.