Establishing rapid diagnostic method and unraveling the pathogenesis offamilial hemophagocytic lymphohistiocytosis

• Project/Area Number: 22591159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: YASUMI Takahiro 京都大学, 大学院・医学研究科, 講師 (00511891)
• Co-Investigator(Kenkyū-buntansha): HEIKE Toshio 京都大学, 大学院・医学研究科, 教授 (90190173)
• Research Collaborator: NISHIKOMORI Ryuta 京都大学, 大学院・医学研究科, 准教授 (70359800)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 原発性免疫不全症 / 家族性血球貪食性リンパ組織球症 / 迅速診断法 / 家族性血球貪食症候群 / 迅速診断 / iPS細胞

Research Abstract

We established a new rapid screening test for FHL3/4/5 by detecting intra-platelet expression of munc13-4/syntaxin11/munc18-2 proteins and found that combinination ofCTL degranulation and munc13-4 expression assays is very useful for finding atypical, late-onset cases of FHL3. We also found that FHL can be clinically differentiated from certain types of secondary HLH cases by comparing levels of serum lactate dehydrogenase, sIL-2R, ferritin, and lymphocyte/neutrophil ratio in peripheral blood at early phase of the disease.

Research Products

• [Journal Article] Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell- free conditions. (2013)
  • Author(s): Yanagimachi MD, Niwa A, Tanaka T, Ozaki F, Nishimoto S, Murata Y, Yasumi T, Ito J, Tomida S, Oshima K, Asaka I, Goto H, Heike T, Nakahata T, Saito MK
  • Journal Title: PLoS ONE Volume: 8(4) Issue: 4 Pages: e59243-e59243
  • DOI: 10.1371/journal.pone.0059243
  • NAID: 120005244458
  • Peer Reviewed
• [Journal Article] 家族性血球貪食症候群のスクリーニング検査 (2013)
  • Author(s): 八角高裕
  • Journal Title: 血液フロンティア Volume: 23 Pages: 27-32
• [Journal Article] Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis (2012)
  • Author(s): Nishi M, Nishimura R, Suzuki N, Sawada A, Okamura T, Fujita N, Kanai R, Yano J, Adachi S, Yasumi T, Sato E, Yasutomo K, Ishii E, Ohga S
  • Journal Title: Am J Hematol Volume: 87(6):637-9 Issue: 6 Pages: 637-639
  • DOI: 10.1002/ajh.23190
  • Peer Reviewed
• [Journal Article] Hematopoietic stem cell transplantation with reduced intensity conditioning from a family haploidentical donor in an infant with familial hemophagocytic lymphohistocytosis (2011)
  • Author(s): Ohta H, Miyashita E, Hirata I, Matsumura R, Yoshida H, Hashii Y, Higashiura T, Yasumi T, Murata Y, Heike T, Yang X, Kanegane H, Ohara O, Ozono K
  • Journal Title: Int J Hematol Volume: 94(3):285-90 Issue: 3 Pages: 285-290
  • DOI: 10.1007/s12185-011-0916-6
  • NAID: 10029694397
  • Peer Reviewed
• [Journal Article] Rapid diagnosis of familial hemophagocytic lymphohistiocytosis type 3 (FHL3) by flow cytometric detection of intraplatelet Munc 13-4 protein. (2011)
  • Author(s): Murata Y., Yasumi T., Shirakawa R., Izawa K., Sakai H., Abe J., Tanaka N., Kawai T., Oshima K., Saito M., Nishikomori R., Ohara O.、Ishii E., Nakahata T., Horiuchi H., Heike T.
  • Journal Title: Blood Volume: 118 Issue: 5 Pages: 1225-1230
  • DOI: 10.1182/blood-2011-01-329540
  • Peer Reviewed
• [Journal Article] Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes (2010)
  • Author(s): Nagai K, Yamamoto K, Fujiwara H, An J, Ochi T, Suemori K, Yasumi T, Tauchi H, Koh K, Sato M, Morimoto A, Heike T, Ishii E, Yasukawa M
  • Journal Title: PLoS One Volume: 5(11):e14173 Issue: 11 Pages: e14173-e14173
  • DOI: 10.1371/journal.pone.0014173
  • Peer Reviewed
• [Journal Article] Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes. (2010)
  • Author(s): Nagai, N., Yamamoto, K., Fujiwara, H., An, J., Ochi, T., Suemori, K., Yasumi, T., Tauchi, H., Koh, K., Sato, M., Morimoto, A., Heike, T., Ishii, E., Yasukawa, M.
  • Journal Title: PloS One Volume: 5
  • Peer Reviewed
• [Presentation] 一般検査から見た FHL/二次性 HLH の特徴と病態の考察 (2013)
  • Author(s): 八角高裕
  • Organizer: 第8回血球貪食症候群研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-16
• [Presentation] Late-onset FHL3: 2 症例の検討 (2013)
  • Author(s): 堀雅之
  • Organizer: 第8回血球貪食症候群研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-16
• [Presentation] Familial Hemophagocytic Lymphohistiocytosis may Present with Atypical Features in Adolescence and Adulthood (2013)
  • Author(s): YASUMI T
  • Organizer: The 4thJSH International Symposium
  • Place of Presentation: Matsuyama
• [Presentation] 血球貪食性リンパ組織球症の病態解明に向けて (2013)
  • Author(s): 八角高裕
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島
• [Presentation] 一般検査から見たFHL/二次性HLHの特徴と病態の考察 (2013)
  • Author(s): 八角高裕
  • Organizer: 第8回血球貪食症候群研究会
  • Place of Presentation: ベルサール八重洲
• [Presentation] Late-onset FHL3: 2症例の検討 (2013)
  • Author(s): 堀雅之、八角高裕
  • Organizer: 第8回血球貪食症候群研究会
  • Place of Presentation: ベルサール八重洲
• [Presentation] 血球貪食性リンパ組織球症の病態解明に向けて (2013)
  • Author(s): 八角高裕
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島市文化交流会館
  • Invited
• [Presentation] Current status and future direction (2012)
  • Author(s): YASUMI T. Diagnosing FHLs among HLHs
  • Organizer: 第54回日本小児血液・がん学会
  • Place of Presentation: 横浜
• [Presentation] Diagnosing FHLs among HLHs: Current status and future direction (2012)
  • Author(s): 八角高裕
  • Organizer: 第54回日本小児血液・がん学会
  • Place of Presentation: パシフィコ横浜
  • Invited
• [Presentation] フローサイトメトリーを用いた家族性血球貪食症候群Type3(FHL3)の迅速診断 (2010)
  • Author(s): 八角高裕
  • Organizer: 第113回日本小児科学会総会
  • Place of Presentation: 岩手県民情報交流センター(盛岡)
  • Year and Date: 2010-04-24
• [Book] 診断と治療社自己炎症性疾患・自然免疫不全症とその周辺疾患 (2012)
  • Author(s): 近藤直実・平家俊男
  • Total Pages: 280
• [Book] 自己炎症性疾患・自然免疫不全症とその周辺疾患 (2012)
  • Author(s): 八角高裕
  • Total Pages: 279
  • Publisher: 診断と治療社