Comprehensive analysis using metabolome profiling for investigating new biomarkers associated with the pathophysiology of acute viral encephalopathy

• Project/Area Number: 26461581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nagoya University
• Principal Investigator: Ito Yoshinori 名古屋大学, 医学系研究科, 准教授 (20373491)
• Co-Investigator(Kenkyū-buntansha): 川田 潤一 名古屋大学, 医学部附属病院, 助教 (20532831)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 急性脳症 / ヒトヘルペスウイルス6型 / インフルエンザ / バイオマーカー / キヌレニン / キノリン酸 / インフルエンザ脳症 / 低分子代謝物 / ヒトヘルペス6型脳症

Outline of Final Research Achievements

Influenza-associated encephalopathy and human herpesvirus 6 encephalopathy are common forms of acute encephalitis/encephalopathy in Japan. Comprehensive metabolome profiling, which can analyze around 3,000 metabolites, was applied to discover new aspects of its disease pathophysiology and new potential biomarkers.
As a result of metabolome profiling, kynurenine and quinolinic acid were selected as potential metabolites associated with the pathophysiology of those two encephalopathies. Trans-endothelial electrical resistance of the in vitro blood brain barrier model was significantly decreased after quinolinic acid treatment in culture.

Research Products

• [Journal Article] Cytomegalovirus (CMV) monitoring after liver transplantation: comparison of the CMV pp65 antigenemia assay with real-time PCR calibrated to the WHO international standard. (2016)
  • Author(s): Kamei H, Ito Y, Onishi Y, Suzuki M, Imai H, Kurata N, Hori T, Tainaka T, Uchida H, Ogura Y.
  • Journal Title: Ann Transpl Volume: 21 Pages: 131-136
  • DOI: 10.12659/aot.895677
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic values for the viral load in peripheral blood mononuclear cells of patients with chronic active Epstein-Barr virus disease (2016)
  • Author(s): Ito Y, Suzuki M, Kawada J, Kimura H
  • Journal Title: Journal of infection and chemotherapy Volume: 22 Issue: 4 Pages: 268-71
  • DOI: 10.1016/j.jiac.2015.11.002
  • Peer Reviewed
• [Journal Article] Identification of Viruses in Cases of Pediatric Acute Encephalitis and Encephalopathy Using Next-Generation Sequencing (2016)
  • Author(s): Kawada, J. Okuno, Y. Torii, Y. Okada, R. Hayano, S. Ando, S. Kamiya, Y. Kojima, S. Ito, Y.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 33452-33452
  • DOI: 10.1038/srep33452
  • Peer Reviewed / Open Access
• [Journal Article] A case of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with severe cardiac complications. (2016)
  • Author(s): Kawamura Y. Miura H. Matsumoto Y. Uchida H. Kudo K. Hata T. Ito Y. Kimura H. Yoshikawa T.
  • Journal Title: BMC Pediatr Volume: 16(1) Issue: 1 Pages: 172-172
  • DOI: 10.1186/s12887-016-0718-3
  • Peer Reviewed / Open Access
• [Journal Article] Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells (2016)
  • Author(s): Ando S, Kawada J, Watanabe T, Suzuki M, Sato Y, Torii Y, Asai M, Goshima F, Murata T, Shimizu N, Ito Y, Kimura H
  • Journal Title: Oncotarget Volume: 7 Issue: 47 Pages: 76793-76805
  • DOI: 10.18632/oncotarget.12529
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of circulating human and viral microRNAs in patients with congenital cytomegalovirus infection (2016)
  • Author(s): Kawano, Y. Kawada, J. Kamiya, Y. Suzuki, M. Torii, Y. Kimura, H. Ito, Y.
  • Journal Title: Journal of perinatology Volume: 36 Issue: 12 Pages: 1101-1105
  • DOI: 10.1038/jp.2016.157
  • Peer Reviewed
• [Journal Article] Primary psoas abscess caused by group A streptococcus in a child: Case report with microbiologic findings (2016)
  • Author(s): Kamiya Y, Hasegawa T, Takegami Y, Horiba K, Ando S, Torii Y, Kidokoro H, Kato T, Natsume J, Kawada JI, Ito Y
  • Journal Title: J Infect Chemother Volume: 22 Issue: 12 Pages: 811-814
  • DOI: 10.1016/j.jiac.2016.06.011
  • Peer Reviewed
• [Journal Article] The first point prevalence survey of healthcare-associated infection and antimicrobial use in a Japanese university hospital: a pilot study. (2016)
  • Author(s): Morioka H, Hirabayashi A, Iguchi M, Tomita Y, Kato D, Sato N, Hyodo M, Kawamura N, Sadomoto T, Ichikawa K, Inagaki T, Kato Y, Kouyama Y, Ito Y, Yagi T.
  • Journal Title: Am J Infect Control Volume: 44(7) Issue: 7 Pages: e119-e123
  • DOI: 10.1016/j.ajic.2016.03.045
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of immunization with live-attenuated and inactivated vaccines for pediatric liver transplantation recipients (2015)
  • Author(s): Kawano Y, Suzuki M, Kawada J, Kimura H, Kamei H, Ohnishi Y, Ito Y
  • Journal Title: Vaccine Volume: 33 Issue: 12 Pages: 1440-5
  • DOI: 10.1016/j.vaccine.2015.01.075
  • Peer Reviewed
• [Journal Article] Choreito formula for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. (2015)
  • Author(s): Kawashima N, Ito Y, Sekiya Y, Narita A, Okuno Y, Muramatsu H, Irie M, Hama A, Takahashi Y, Kojima S.
  • Journal Title: Biol Blood Marrow Transplant Volume: 21 Issue: 2 Pages: 319-325
  • DOI: 10.1016/j.bbmt.2014.10.018
  • Peer Reviewed
• [Journal Article] Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis (2015)
  • Author(s): Kamiya Y, Kawada J, Kawano Y, Torii Y, Kawabe S, Iwata N, Ito Y
  • Journal Title: Clinical rheumatology. Volume: 34 Issue: 10 Pages: 1705-12
  • DOI: 10.1007/s10067-015-2922-1
  • Peer Reviewed
• [Journal Article] The heat shock protein 90 inhibitor BIIB021 suppresses the growth of T and natural killer cell lymphomas (2015)
  • Author(s): Suzuki M, Takeda T, Nakagawa H, Iwata S, Watanabe T, Siddiquey MN, Goshima F, Murata T, Kawada J, Ito Y, Kojima S, Kimura H
  • Journal Title: Frontiers in microbiology Volume: 6 Pages: 280-280
  • DOI: 10.3389/fmicb.2015.00280
  • Peer Reviewed / Open Access
• [Journal Article] Successful treatment of corticosteroid with antiviral therapy for a neonatal liver failure with disseminated herpes simplex virus infection. (2015)
  • Author(s): Maeba S, Hasegawa S, Shimomura M, Ichimura T, Takahashi K, Motoyama M, Fukunaga S, Ito Y, Ichiyama T, Ohga S.
  • Journal Title: Am J Perinatol Rep Volume: 52 Issue: 02 Pages: e089-e092
  • DOI: 10.1055/s-0034-1398392
  • Peer Reviewed
• [Journal Article] Correlations of programmed death 1 expression and serum IL-6 level with exhaustion of cytomegalovirus-specific T cells after allogeneic hematopoietic stem cell transplantation. (2014)
  • Author(s): Kato T, Nishida T, Ito Y, Murase M, Murata M, Naoe T.
  • Journal Title: Cell Immunol Volume: 288(1-2) Pages: 53-59
  • Peer Reviewed / Open Access
• [Journal Article] Rare occurrence of JAK3 mutations in NK cell neoplasms in Japan (2014)
  • Author(s): Kimura H, Karube K, Ito Y, Hirano K, Suzuki M, Iwata S, Seto M.
  • Journal Title: Leukemia & Lymphoma Volume: 55 Issue: 4 Pages: 962-3
  • DOI: 10.3109/10428194.2013.819577
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus microRNAs in plasma as potential biomarkers for chronic infections: reply to Makarewicz et al. (2014)
  • Author(s): Kawano, Y., Kawada, J., Ito, Y
  • Journal Title: The Journal of infectious diseases Volume: 209 Issue: 8 Pages: 1298-1300
  • DOI: 10.1093/infdis/jit676
  • Peer Reviewed / Open Access
• [Journal Article] Anti-CCR4 monoclonal antibody mogamulizumab for the treatment of EBV-associated T- and NK-cell lymphoproliferative diseases. (2014)
  • Author(s): Kanazawa T, Hiramatsu Y, Iwata S, Siddiquey MN, Sato Y, Suzuki M, Ito Y, Goshima F, Murata T, Kimura H.
  • Journal Title: Clin Cancer Res Volume: 20 Issue: 19 Pages: 5075-84
  • DOI: 10.1158/1078-0432.ccr-14-0580
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lack of presence of the human cytomegalovirus in human glioblastoma. (2013)
  • Author(s): Yamashita Y, Ito Y, Isomura H, Takemura N, Okamoto A, Motomura K, Tsujiuchi T, Natsume A, Wakabayashi T, Toyokuni S, Tsurumi T
  • Journal Title: Mod Pathol Volume: Dec 13 Issue: 7 Pages: 922-9
  • DOI: 10.1038/modpathol.2013.219
  • Peer Reviewed
• [Presentation] 小児血流感染症における病原微生物診断への次世代シーケンサーの応用 (2016)
  • Author(s): 堀場千尋、川田潤一、奥野友介、手塚宜行、鈴木高子、安藤将太郎、神谷泰子、鳥居ゆか、高橋義行、伊藤嘉規
  • Organizer: 第48回日本小児感染症学会総会・学術集会
  • Place of Presentation: 岡山コンベンションセンター(岡山県岡山市)
  • Year and Date: 2016-11-19
• [Presentation] Next-generation sequencing for the identification of viruses in pediatric acute encephalaitis and encephalaopathy. (2016)
  • Author(s): Jun-ichi Kawada, Yusuke Okuno, Yuka Torii, Kazuhiro Horiba, Takako Suzuki, Shotaro Ando, Yasuko Kamiya, Yoshinori Ito
  • Organizer: IDSA 2016
  • Place of Presentation: New Orleans (USA)
  • Year and Date: 2016-10-26
  • Int'l Joint Research
• [Presentation] 肝移植後小児症例における不活性化4価インフルエンザワクチン接種の経験 (2016)
  • Author(s): 鈴木高子、鳥居ゆか、鈴木道雄、神谷泰子、安藤将太郎、堀場千尋、川田潤一、伊藤嘉規
  • Organizer: 第20回日本ワクチン学会学術集会
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 2016-10-22
• [Presentation] メタボローム解析が明らかにしたインフルエンザ脳症における新規バイオマーカー候補 (2016)
  • Author(s): 伊藤嘉規
  • Organizer: 第10回メタボロームシンポジウム
  • Place of Presentation: 鶴岡メタボロームキャンパスレクチャーホール(山形県鶴岡市)
  • Year and Date: 2016-10-19
  • Invited
• [Presentation] 持続性高EBウイルス血症を示す小児生体肝移植症例についての検討 (2016)
  • Author(s): 亀井秀弥、伊藤嘉規、川田潤一、大西康晴、倉田信彦、小倉靖弘
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: グランドプリンスホテル新高輪(東京都港区)
  • Year and Date: 2016-09-29
• [Presentation] 新生児ヘルペス単純ヘルペスウイルスによる母子感染 (2016)
  • Author(s): 伊藤嘉規
  • Organizer: 第52回日本周産期・新生児医学会学術集会
  • Place of Presentation: 富山国際会議場(富山県富山市)
  • Year and Date: 2016-07-16
• [Presentation] 次世代シーケンサーを用いた急性脳炎・脳症の病原ウイルスの検出 (2016)
  • Author(s): 川田潤一、鳥居ゆか、安藤将太郎、鈴木高子、神谷泰子、小島勢二、伊藤嘉規
  • Organizer: 第119回日本小児科学会学術集会
  • Place of Presentation: ロイトン札幌(北海道札幌市)
  • Year and Date: 2016-05-13
• [Presentation] 院内の横断的疫学調査を2014-2015年度に施行して見えてきた課題 (2016)
  • Author(s): 森岡悠、手塚宜行、平林亜希、井口光孝、冨田ゆうか、加藤大三、伊藤嘉規、八木哲也
  • Organizer: 第90回日本感染症学会総会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
  • Year and Date: 2016-04-15
• [Presentation] EBV関連腫瘍におけるトファシチニブの抗腫瘍効果の検討 (2015)
  • Author(s): 安藤将太郎、川田潤一、鈴木道雄、渡辺崇広、鳥居ゆか、吉山裕規、清水則夫、木村宏、伊藤嘉規
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2015-11-22
• [Presentation] 次世代シーケンサーを用いた急性脳炎・脳症患者からの網羅的ウイルス検出の試み (2015)
  • Author(s): 川田潤一、鳥居ゆか、堀場千尋、安藤将太郎、鈴木高子、神谷泰子、伊藤嘉規
  • Organizer: 第47回日本小児感染症学会
  • Place of Presentation: ホテル福島グリーンパレス（福島県福島市）
  • Year and Date: 2015-10-31
• [Presentation] 慢性活動性EBウイルス感染症における診断的意義のある末梢血単核球分画中ウイルスDNA量の解析 (2015)
  • Author(s): 伊藤嘉規、鈴木道雄、川田潤一、木村宏
  • Organizer: 第47回日本小児感染症学会
  • Place of Presentation: ザ・セクトン福島（福島県福島市）
  • Year and Date: 2015-10-31
• [Presentation] EBVによる伝染性単核球症に急性無石性胆嚢炎を合併した男児例 (2015)
  • Author(s): 鈴木道雄、三輪田俊介、服部典子、池田圭、徳永博秀、森田誠、伊藤嘉規、長谷川真司
  • Organizer: 第47回日本小児感染症学会
  • Place of Presentation: コラッセふくしま（福島県福島市）
  • Year and Date: 2015-10-31
• [Presentation] 高フェリチン血症を示すパレコウイルス(HPeV)・エンテロウイルス(EV)関連感染症における血清サイトカイン濃度の検討 (2015)
  • Author(s): 原紳也、加藤耕治、川田潤一、伊藤嘉規
  • Organizer: 第47回日本小児感染症学会
  • Place of Presentation: コラッセふくしま（福島県福島市）
  • Year and Date: 2015-10-31
• [Presentation] The first point prevalence survey of healthcare-associated infections and antimicrobial use in a Japanese university hospital: a pilot study. (2015)
  • Author(s): Hiroshi Morioka, Aki Hirabayashi, Mitsutaka Iguchi, Yuka Tomita, Daizo Kato, Yoshinori Ito, Tetsuya Yagi
  • Organizer: IDWeek 2015
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] Antitumor activity of Tofacitinib on Epstein-Barr virus-associated lymphoma cells. (2015)
  • Author(s): Shotaro Ando, Jun-ichi Kawada, Michio Suzuki, Takahiro Watanabe, Yuka Torii, Takayuki Murata, Hiroshi Kimura, Yoshinori Ito
  • Organizer: 40th Annual International Hepesvirus Workshop
  • Place of Presentation: Boise (USA)
  • Year and Date: 2015-07-25
  • Int'l Joint Research
• [Presentation] EBV infection of human monocytes induces AIM2 inflammasome activation. (2015)
  • Author(s): Jun-ichi Kawada, Yuka Torii, Michio Suzuki, Takayuki Murata, Hironori Yoshiyama, Hiroshi Kimura, Yoshinori Ito
  • Organizer: 40th Annual International Hepesvirus Workshop
  • Place of Presentation: Boise (USA)
  • Year and Date: 2015-07-25
  • Int'l Joint Research
• [Presentation] EBウイルス初感染時のヒト単核球細胞におけるインフラマソーム活性 (2015)
  • Author(s): 鳥居ゆか、安藤将太郎、神谷泰子、川田潤一、村田貴之、吉山裕規、木村宏、伊藤嘉規
  • Organizer: 第29回ヘルペスウイルス研究会
  • Place of Presentation: 長崎にっしょうかん（長崎県長崎市）
  • Year and Date: 2015-06-04
• [Presentation] Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening. (2015)
  • Author(s): Jun-ichi Kawada, Yuka Torii, Yoshihiko Kawano, Michio Suzuki, Yasuko Kamiya, Tomomi Kotani, Fumitaka Kittaka, Hiroshi Kimura and Yoshinori Ito
  • Organizer: 5th International Congenital CMV Conference and 15th International CMV/Beta Herpes Virus Workshop
  • Place of Presentation: Brisbane (Australia)
  • Year and Date: 2015-04-20
  • Int'l Joint Research
• [Presentation] 生体肝移植小児例への移植後の予防接種の効果と課題 (2015)
  • Author(s): 鈴木道雄、河野好彦、鳥居ゆか、安藤将太郎、神谷泰子、川田潤一、木村宏、伊藤嘉規
  • Organizer: 第118回日本小児科学会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-17
• [Presentation] 先天性サイトメガロウイルス感染症に対する経口バルガンシクロビルの治療効果の検討 (2015)
  • Author(s): 川田潤一、鈴木高子、安藤将太郎、神谷泰子、鈴木道雄、鳥居ゆか、木村宏、伊藤嘉規
  • Organizer: 第89回日本感染症学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-04-16
• [Presentation] 血漿中miRNA定量による先天性サイトメガロウイルス感染症のバイオメーカーの検討 (2015)
  • Author(s): 河野好彦、川田潤一、鈴木高子、安藤将太郎、神谷泰子、鈴木道雄、鳥居ゆか、木村宏、伊藤嘉規
  • Organizer: 第89回日本感染症学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-04-16
• [Presentation] EBウイルスの単球細胞におけるInflammasome活性化の解析 (2014)
  • Author(s): 鳥居ゆか、川田潤一、村田貴之、吉山裕規、鈴木道雄、木村宏、伊藤嘉規
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜会議センター（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] EBV関連T/NKリンパ腫・リンパ増殖性疾患に対するヒト化抗CCR4抗体の効果の解析 (2014)
  • Author(s): 鈴木道雄、岩田誠子、Mohanmmed NA Siddiquey、佐藤好隆、伊藤嘉規、五島典、村田貴之、木村宏
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜会議センター（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 小児期生体肝移植例に対する移植後ワクチン接種の検討 (2014)
  • Author(s): 鈴木道雄、河野好彦、鳥居ゆか、鈴木高子、安藤将太郎、神谷泰子、川田潤一、木村宏、伊藤嘉規
  • Organizer: 第46回日本小児感染症学会総会・学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] 先天性サイトメガロウイルス感染症におけるバイオマーカーとしての血漿中ウイルス由来・ヒト由来miRNAの解析 (2014)
  • Author(s): 河野好彦、川田潤一、鈴木高子、安藤将太郎、神谷泰子、鈴木道雄、鳥居ゆか、伊藤嘉規
  • Organizer: 第46回日本小児感染症学会総会・学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] バルガンシクロビルで治療した先天性サイトメガロウイルス感染症でのウイルス量の検討 (2014)
  • Author(s): 川田潤一、鈴木高子、安藤将太郎、神谷泰子、鈴木道雄、鳥居ゆか、木村宏、伊藤嘉規
  • Organizer: 第46回日本小児感染症学会総会・学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] Inhibitor B11B021 suppresses cell growth of EBV-associated T and natural killer cell lymphoma. (2014)
  • Author(s): Michio Suzuki, Tadashi Takeda, Hikaru Nakagawa, Seiko Iwata, Mohammed NA Siddiquey, Fumi Goshima, Yoshiknori Ito, Takayuki Murata, Tatsuya Tsurumi, Hiroshi Kimura
  • Organizer: IHW 2014
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2014-07-19 – 2014-07-23
• [Presentation] Oral valganciclovir for congenital cytomegalovirus infection identified on newborn hearing screening (2014)
  • Author(s): Jun-ichi Kawada, Michio Suzuki, Yuka Torii, Yoshihiko Kawano, Tomomi Kotani, Fumitaka Kikkawa, Hiroshi Kimura, Yoshinori Ito
  • Organizer: IHW 2014
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2014-07-19 – 2014-07-23
• [Presentation] Metabolome analysis reveals involvement of the tryptophan-kynurenine pathway in human herpesvirus 6 encephalopathy (2014)
  • Author(s): Yoshinori Ito, Yoshihiko Kawano, Yuka Torii, Hajime Sato, Kazunori Sasaki, Tamaki Fujimori
  • Organizer: IHW 2014
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2014-07-19 – 2014-07-23
• [Presentation] 国際標準物質を用いたEpstein-Barrウイルス・サイトメガロウイルス定量PCR系の標準化 (2014)
  • Author(s): 伊藤嘉規、河野好彦、鳥居ゆか、安藤将太郎、神谷泰子、鈴木道雄、川田潤一、木村宏
  • Organizer: 第88回日本感染症学会学術講演会
  • Place of Presentation: ヒルトン福岡シーホーク（福岡県福岡市）
  • Year and Date: 2014-06-18 – 2014-06-20