Analysis of Epstein-Barr virus (EBV)-infected T cells in EBV associated hemophagocytic lymphohistiocytosis

• Project/Area Number: 24591542
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kanazawa University
• Principal Investigator: WADA Taizo 金沢大学, 大学病院, 講師 (30313646)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 小児科学 / EBウイルス / 血球貪食性リンパ組織球症 / Epstein-Barrウイルス

Outline of Final Research Achievements

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is characterized by ectopic EBV infection in CD8+ T cells and their clonal proliferation. We demonstrate that EBV-infected cells can be detected as highly activated CD5-/dim CD8+ T cells that often react with a specific TCR Vβ monoclonal antibody in patients with EBV-HLH, who exhibit characteristic profiles of serum cytokines. Although down-regulation of CD5 in CD8+ T cells is not specific for EBV-HLH, the combined approach of our flow cytometric analysis including TCR Vβ repertoire and cytokine profile analysis may be useful in diagnosis and follow-up of patients with EBV-HLH.

Research Products

• [Journal Article] Fecal eosinophil-derived neurotoxin in cow's milk-sensitive enteropathy: A case report (2015)
  • Author(s): Wada T, Matsuda Y, Muraoka M, Toma T, Yachie A.
  • Journal Title: Allergology International Volume: 64 Issue: 1 Pages: 99-100
  • DOI: 10.1016/j.alit.2014.11.001
  • NAID: 130004873130
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Severe congenital neutropenia caused by the ELANE gene mutation in a Vietnamese boy with misdiagnosis of tuberculosis and autoimmune neutropenia: a case report. (2015)
  • Author(s): Vu QV, Wada T, Tran TT, Ngo DN, Van Dinh T, Nguyen CH, Le HT, Yachie A, Nguyen SN.
  • Journal Title: BMC Hematol Volume: 15 Issue: 1 Pages: 2-2
  • DOI: 10.1186/s12878-015-0020-x
  • Peer Reviewed / Open Access
• [Journal Article] Successful treatment of idiopathic colitis related to XIAP deficiency with allo-HSCT using reduced-intensity conditioning. (2015)
  • Author(s): Tsuma Y, Imamura T, Ichise E, Sakamoto K, Ouchi K, Osone S, Ishida H, Wada T, Hosoi H.
  • Journal Title: Pediatr Transplant Volume: 19 Issue: 1
  • DOI: 10.1111/petr.12405
  • Peer Reviewed
• [Journal Article] Intermittent X-linked thrombocytopenia with a novel WAS gene mutation. (2014)
  • Author(s): Wada T, Itoh M, Maeba H, Toma T, Niida Y, Saikawa Y, Yachie A.
  • Journal Title: Pediatr Blood Cancer Volume: 61 Issue: 4 Pages: 746-748
  • DOI: 10.1002/pbc.24787
  • NAID: 120005411676
  • Peer Reviewed / Open Access
• [Journal Article] Increased expression of epidermal thymic stromal lymphopoietin in inflammatory peeling skin syndrome. (2014)
  • Author(s): Wada T, Toma T, Hamaguchi Y, Yachie A.
  • Journal Title: J Dermatol Volume: 41 Issue: 5 Pages: 448-449
  • DOI: 10.1111/1346-8138.12449
  • NAID: 120005463364
  • Peer Reviewed
• [Journal Article] Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia. (2014)
  • Author(s): Vu QV, Wada T, Le HT, Le HT, Van Nguyen AT, Osamu O, Yachie A, Nguyen SN.
  • Journal Title: BMC Pediatr Volume: 14 Issue: 1 Pages: 129-129
  • DOI: 10.1186/1471-2431-14-129
  • Peer Reviewed / Open Access
• [Journal Article] Munc13-4 deficiency with CD5 downregulation on activated CD8+ T cells. (2014)
  • Author(s): Wada T, Yasumi T, Toma T, Hori M, Maeda S, Umeda K, Heike T, Adachi S, Usami I, Yachie A.
  • Journal Title: Pediatr Int Volume: 56 Issue: 4 Pages: 605-608
  • DOI: 10.1111/ped.12290
  • Peer Reviewed
• [Journal Article] Successful treatment of systemic cytomegalovirus infection in severe combined immunodeficiency using allogeneic bone marrow transplantation followed by adoptive immunotherapy. (2014)
  • Author(s): Koura U, Sakaki-Nakatsubo H, Otsubo K, Nomura K, Oshima K, Ohara O, Wada T, Yachie A, Imai K, Morio T, Miyawaki T, Kanegane H.
  • Journal Title: J Investig Allergol Clin Immunol Volume: 24 Pages: 200-202
  • Peer Reviewed
• [Journal Article] Elevation of fecal eosinophil-derived neurotoxin in infants with food protein-induced enterocolitis syndrome. (2014)
  • Author(s): Wada T, Toma T, Muraoka M, Matsuda Y, Yachie A.
  • Journal Title: Pediatr Allergy Immunol Volume: 25 Issue: 6 Pages: 617-619
  • DOI: 10.1111/pai.12254
  • NAID: 120005478699
  • Peer Reviewed
• [Journal Article] Shiga toxin-2 enhances heat-shock-induced cell death in cultured and primary glial cells. (2014)
  • Author(s): Sugimoto N, Toma T, Shimizu M, Kuroda M, Wada T, Yachie A.
  • Journal Title: Cell Biol Toxicol Volume: 30 Issue: 5 Pages: 289-299
  • DOI: 10.1007/s10565-014-9286-1
  • Peer Reviewed / Open Access
• [Journal Article] Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency (2014)
  • Author(s): Wada T, Kanegane H, Ohta K, Katoh F, Imamura T, Nakazawa Y, Miyashita R, Hara J, Hamamoto K, Yang X, Filipovich AH, Marsh RA, Yachie A.
  • Journal Title: Cytokine Volume: 65 Issue: 1 Pages: 74-78
  • DOI: 10.1016/j.cyto.2013.09.007
  • NAID: 120005349175
  • Peer Reviewed
• [Journal Article] Alu-mediated large deletion of the CDSN gene as a cause of peeling skin disease. (2013)
  • Author(s): Wada T, Matsuda Y, Muraoka M, Toma T, Takehara K, Fujimoto M, Yachie A.
  • Journal Title: Clin Genet Volume: in press Issue: 4 Pages: 383-386
  • DOI: 10.1111/cge.12294
  • NAID: 120005349177
  • Peer Reviewed
• [Journal Article] Rapid Detection of Intracellular p47phox and p67phox by Flow Cytometry; Useful Screening Tests for Chronic Granulomatous Disease. (2013)
  • Author(s): Wada T
  • Journal Title: J Clin Immunol. Volume: 33 Issue: 4 Pages: 857-864
  • DOI: 10.1007/s10875-012-9859-9
  • Peer Reviewed
• [Journal Article] Cytokine profiles in children with primary Epstein-Barr virus infection. (2013)
  • Author(s): Wada T, Muraoka M, Yokoyama T, Toma T, Kanegane H, Yachie A.
  • Journal Title: Pediatr Blood Cancer Volume: 60 Issue: 7
  • DOI: 10.1002/pbc.24480
  • NAID: 120005302292
  • Peer Reviewed
• [Journal Article] Expansion of a liver-infiltrating cytotoxic T-lymphocyte clone in concert with the development of hepatitis-associated aplastic anaemia (2013)
  • Author(s): (Yasuhiro Ikawa), Ryosei Nishimura, Rie Kuroda, Shintaro Mase, Raita Araki, Hideaki Maeba, Taizo Wada, Tomoko Toma, Shoichi Koizumi, Akihiro Yachie
  • Journal Title: British Journal of Haematology Volume: 161 Issue: 4 Pages: 599-602
  • DOI: 10.1111/bjh.12259
  • Peer Reviewed
• [Journal Article] A case series of CAEBV of children and young adults treated with reduced-intensity conditioning and allogeneic bone marrow transplantation: a single-center study. (2013)
  • Author(s): Watanabe Y, Sasahara Y, Satoh M, Looi CY, Katayama S, Suzuki T, Suzuki N, Ouchi M, Horino S, Moriya K, Nanjyo Y, Onuma M, Kitazawa H, Irie M, Niizuma H, Uchiyama T, Rikiishi T, Kumaki S, Minegishi M, Wada T, Yachie A, Tsuchiya S, Kure S.
  • Journal Title: Eur J Haematol Volume: 91 Issue: 3 Pages: 242-248
  • DOI: 10.1111/ejh.12151
  • Peer Reviewed
• [Journal Article] Successful cord blood transplantation after repeated transfusions of unmobilized neutrophils in addition to antifungal treatment in an infant with chronic granulomatous disease complicated by invasive pulmonary aspergillosis. (2013)
  • Author(s): Shigemura T, Nakazawa Y, Yoshikawa K, Hirabayashi K, Saito S, Kobayashi N, Sakashita K, Shiohara M, Wada T, Shimodaira S, Agematsu K and Koike K.
  • Journal Title: Transfusion Volume: 54 Issue: 3 Pages: 516-21
  • DOI: 10.1111/trf.12325
  • Peer Reviewed
• [Journal Article] Down-regulation of CD5 expression on activated CD8+ T cells in familial hemophagocytic lymphohistiocytosis with perforin gene mutations. (2013)
  • Author(s): Wada T, Sakakibara Y, Nishimura R, Toma T, Ueno Y, Horita S, Tanaka T, Nishi M, Kato K, Yasumi T, Ohara O, Yachie A.
  • Journal Title: Hum Immunol Volume: 74 Issue: 12 Pages: 1579-1585
  • DOI: 10.1016/j.humimm.2013.09.001
  • NAID: 120005349176
  • Peer Reviewed
• [Journal Article] Aberrant glycosylation of IgA in Wiskott-Aldrich syndrome and X-linked thrombocytopenia. (2013)
  • Author(s): Shimizu M, Kanegane H, Wada T, Motoyoshi Y, Morio T, Candotti F, Yachie A.
  • Journal Title: J Allergy Clin Immunol. Volume: 131 Issue: 2 Pages: 587-590
  • DOI: 10.1016/j.jaci.2012.08.040
  • Peer Reviewed
• [Journal Article] Successful bone marrow transplantation with reduced intensity conditioning in a patient with delayed-onset adenosine deaminase deficiency. (2013)
  • Author(s): Kanegane H, Taneichi H, Nomura K, Wada T, Yachie A, Imai K, Ariga T, Santisteban I, Hershfield MS, Miyawaki T.
  • Journal Title: Pediatr Transplant. Volume: 71 Issue: 1
  • DOI: 10.1111/j.1399-3046.2012.01762.x
  • Peer Reviewed
• [Journal Article] Clinical and immunophenotypic features of atypical complete DiGeorge syndrome (2013)
  • Author(s): Vu QV, Wada T, Toma T, Tajima H, Maeda M, Tanaka R, Oh-Ishi T, Yachie A.
  • Journal Title: Pediatr Int Volume: 55 Issue: 1 Pages: 2-6
  • DOI: 10.1111/j.1442-200x.2012.03722.x
  • Peer Reviewed
• [Journal Article] Agranulocytosis after infectious mononucleosis (2013)
  • Author(s): Yokoyama T, Tokuhisa Y, Toga A, Fujiki T, Sakakibara Y, Mase S, Araki R, Nishimura R, Wada T, Fuseda T, Kato E, Yachie A.
  • Journal Title: J Clin Virol Volume: 56 Issue: 3 Pages: 271-273
  • DOI: 10.1016/j.jcv.2012.11.016
  • Peer Reviewed
• [Journal Article] Delayed onset adenosine deaminase deficiency associated with acute disseminated encephalomyelitis. (2012)
  • Author(s): Nakaoka H, Kanegane H, Taneichi H, Miya K, Yang X, Nomura K, Takezaki S, Yamada M, Ohara O, Kamae C, Imai K, Nonoyama S, Wada T, Yachie A, Hershfield MS, Ariga T, Miyawaki T.
  • Journal Title: Int J Hematol. Volume: 95 Issue: 6 Pages: 692-696
  • DOI: 10.1007/s12185-012-1055-4
  • NAID: 10030793746
  • Peer Reviewed
• [Journal Article] Multiple reversions of an IL2RG mutation restore combined immunodeficiency patient. (2012)
  • Author(s): Kawai T., Saito M., Nishikomori R., Yasumi T., Izawa K., Murakami T., Okamoto N., Mori Y., Nakagawa N., Imai K., Nonoyama S., Wada T., Yatie A., Oomori K., Nakahata T., Heike T.
  • Journal Title: J. Clin. Immunol Volume: 32(4) Issue: 4 Pages: 690-7
  • DOI: 10.1007/s10875-012-9684-1
  • Peer Reviewed
• [Journal Article] Clonal expansion of Epstein-Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions. (2012)
  • Author(s): Wada T, Toga A, Sakakibara Y, Toma T, Shigemura T, Agematsu K, Yachie A.
  • Journal Title: Int J Hematol Volume: 96(4) Issue: 4 Pages: 443-9
  • DOI: 10.1007/s12185-012-1156-0
  • NAID: 10031126735
  • Peer Reviewed
• [Presentation] FPIESにおける食物負荷後の便中EDN・カルプロテクチン・IgAの推移 (2014)
  • Author(s): 和田泰三、東馬智子、村岡正裕、松田裕介、榊原康久、谷内江昭宏
  • Organizer: 第51回日本小児アレルギー学会
  • Place of Presentation: 四日市文化会館（四日市）
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] Different leaky phenotype in two siblings with X-linked severe combined immunodeficiency (2014)
  • Author(s): Taizo Wada, Tomoko Toma, Masahiro Yasui, Masami Inoue, Keisei Kawa, Kohsuke Imai, Tomohiro Morio, and Akihiro Yachie
  • Organizer: 16th Biennal Meeting of the European Society for ImmunodeficienciesPrague, Czech Republic
  • Place of Presentation: Prague Congress Centre (Prague, Czech Republic)
  • Year and Date: 2014-10-29 – 2014-11-01
• [Presentation] 炎症性peeling skin syndromeにおける表皮TSLPの発現亢進 (2014)
  • Author(s): 和田泰三、松田裕介、村岡正裕、榊原康久、東馬智子、濱口儒人、谷内江昭宏
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-05-09 – 2014-05-11
• [Presentation] XIAP欠損症における血清IL-18の持続高値 (2014)
  • Author(s): 和田泰三、金兼弘和、太田和秀、谷内江昭宏
  • Organizer: 第117回日本小児科学会学術集会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2014-04-11 – 2014-04-13
• [Presentation] 異なるphenotypeを示した非典型的XSCIDの兄弟例 (2014)
  • Author(s): 和田泰三、村岡正裕、東馬智子、谷内江昭宏、今井耕輔、森尾友宏、安井昌博、井上雅美、河敬世
  • Organizer: 第7回日本免疫不全症研究会
  • Place of Presentation: レソラNTT夢天神ホール（福岡）
• [Presentation] 蚊刺過敏症のNK細胞におけるCD160発現とsCD160の解析 (2014)
  • Author(s): 和田泰三、村岡正裕、東馬智子、谷内江昭宏
  • Organizer: 第23回EBウイルス感染症研究会
  • Place of Presentation: 東京ステーションコンファレンス（東京）
• [Presentation] フローサイトメトリーによるp47phox/p67phox解析と慢性肉芽腫症の病型診断 (2013)
  • Author(s): 和田泰三、村岡正裕、東馬智子、今井剛、重村倫成、上松一永、原口浩平、森内浩幸、森尾友宏、谷内江昭宏
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島国際会議場（広島）
• [Presentation] 血球貪食を伴うPIDとサイトカイン (2013)
  • Author(s): 和田泰三
  • Organizer: 第4回関東甲越免疫不全症研究会
  • Place of Presentation: 東京ステーションコンファレンス（東京）
  • Invited
• [Presentation] CDSN遺伝子に巨大欠失を認めたpeeling skin syndromeの一女児例 (2013)
  • Author(s): 和田泰三、松田裕介、村岡正裕、東馬智子、大石勉、藤本学、竹原和彦、谷内江昭宏
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] 便中蛋白による慢性肉芽腫症における腸管炎症の評価 (2013)
  • Author(s): 和田泰三、松田裕介、村岡正裕、東馬智子、谷内江昭宏
  • Organizer: 第45回日本小児感染症学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
• [Presentation] EBV-HLHの免疫病態 (2012)
  • Author(s): 和田泰三
  • Organizer: 日本小児感染症学会総会・学術集会
  • Place of Presentation: 西日本総合展示場（福岡県）
• [Presentation] γδT細胞感染型の慢性活動性EBV感染症3例におけるγδT細胞の解析 (2012)
  • Author(s): 和田泰三、榊原康久、栂暁子、東馬智子、長谷川稔、田中理砂、大石勉、重村倫成、上松一永、谷内江昭宏
  • Organizer: 日本小児科学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県）