Evaluation of the host immune response to Cryptococcus and of the association between fungal organ directivity and host immune reaction.

• Project/Area Number: 26461508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nagasaki University
• Principal Investigator: KOHNO Shigeru 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (80136647)
• Co-Investigator(Kenkyū-buntansha): 泉川 公一 長崎大学, 医歯薬学総合研究科(医学系), 教授 (20404212)
• Research Collaborator: SAIJO Tomomi
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: クリプトコック髄膜炎 / 抗GM-CSF抗体 / クリプトコックス抗原 / 肺クリプトコックス症 / BALF中クリプトコックス抗原 / クリプトコックス症 / MLST / 病原性評価 / 中枢神経クリプトコックス症 / Cryptococcus neoformans / Cryptococcus gattii / GM-CSF / STAT5 / 抗GM-CSF自己抗体

Outline of Final Research Achievements

Cryptococcus is a pathogenic yeast which causes serious invasive fungal disease not only in immunocompromised patients but also in immunocompetent patients, while the mechanism of the development of cryptococcosis in terms of both fungal virulence factors and host defense systems have much remained unknown. Although detection of cryptococcal glucuronoxylomannan (GXM) antigen in the serum and/or in the cerebrospinal fluid is a useful method for the diagnosis of cryptococcosis, GXM antigen in the serum sometimes remains negative in a patient with a small lesion of pulmonary cryptococcosis.
We evaluated that anti GM-CSF auto antibodies in the host serum are associated with the development of cryptococcal meningitis. The rate of GXM-positive BALF samples was higher than the rate for serum samples, especially for patients with pulmonary lesion diameters <25 mm.

Research Products

• [Journal Article] Current recommendations and importance of antifungal stewardship for the management of invasive candidiasis. (2015)
  • Author(s): Miyazaki T, Kohno S
  • Journal Title: Expert Rev Anti Infect Ther. Volume: 13 Issue: 9 Pages: 1171-1183
  • DOI: 10.1586/14787210.2015.1058157
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan (2015)
  • Author(s): Shigeru Kohno, Hiroshi Kakeya, et al.
  • Journal Title: Journal of Infections and Chemotherapy Volume: 21 Issue: 1 Pages: 23-30
  • DOI: 10.1016/j.jiac.2014.08.025
  • Peer Reviewed / Open Access
• [Journal Article] Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies Are a Risk Factor for Central Nervous System Infection by Cryptococcus gattii in Otherwise Immunocompetent Patients (2014)
  • Author(s): Tomomi Saijo, Jianghan Chen, et al.
  • Journal Title: mBio Volume: 5 Issue: 2
  • DOI: 10.1128/mbio.00912-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 真菌感染症研究の進歩と将来展望 (2016)
  • Author(s): 河野 茂
  • Organizer: 第90回日本感染症学会総会・学術講演会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-04-15
• [Presentation] 当院におけるクリプトコックス臨床分離株のMLST解析 (2016)
  • Author(s): 芦澤 信之、西條知見、三原 智、島村真太郎、山本和子、今村圭文、宮崎泰可、泉川公一 、栁原克紀、河野 茂、迎 寛
  • Organizer: 第22回真菌症フォーラム学術集会
  • Place of Presentation: TFTビル (東京都江東区)
• [Presentation] 医真菌学会の将来展望 (2015)
  • Author(s): 河野 茂
  • Organizer: 第59回日本医真菌学会総会・学術集会
  • Place of Presentation: ホテルさっぽろ芸文館（北海道札幌市）
  • Year and Date: 2015-10-10
• [Presentation] 日常診療で遭遇する深在性真菌症の診断と治療 (2015)
  • Author(s): 河野 茂
  • Organizer: 第112回日本内科学会講演会
  • Place of Presentation: みやこめっせ（京都府京都市）
  • Year and Date: 2015-04-12
• [Presentation] 真菌症フォーラム16年の軌跡 (2015)
  • Author(s): 河野 茂
  • Organizer: 真菌症フォーラム第16回学術集会
  • Place of Presentation: 第一ホテル東京(東京都港区新橋)
  • Year and Date: 2015-02-14