• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

自己識別機構の破綻をきたす免疫不全症の病態解明と原因遺伝子同定

Publicly Offered Research

Project AreaImmunological Self Recognition and its Disorders
Project/Area Number 22021049
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Defense Medical College

Principal Investigator

野々山 恵章  防衛医科大学校, 医学教育部・医学科専門課程, 教授 (40280961)

Co-Investigator(Kenkyū-buntansha) 大嶋 宏一  京都大学, iPS細胞研究所, 特定研究員 (60525377)
今井 耕輔  東京医科歯科大学, 大学院・医歯学総合研究科, 准教授 (90332626)
長瀬 隆弘  (財)かずさDNA研究所, ヒトゲノム研究部, 室長 (10211442)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 2011: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2010: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywords免疫学 / 遺伝子 / 移植・再生医療 / 発生・分化 / 感染症
Research Abstract

T細胞、B細胞新生能のマーカーであるTREC,KRECを、微量の乾燥濾紙血からrealtimePCRで定量的に測定する技術を確立した。T細胞分化障害である重症複合型免疫不全症(SCID)ではTRECが陰性になり、B細胞分化障害である伴性劣性無γ-グロブリン血症(XLA)ではKRECが陰性になることを見出し、現行の新生児スクリーニングで採取される微量の乾燥濾紙血(ガスリー血)で、両疾患をスクリーニング出来ることも示した。ATM,DiGeorge症候群,Rac2欠損症などの原発性免疫不全症でもTREC/KRECが陰性になることを見出した。原因不明の免疫不全症であるCommon variable immunodeficiency(CVID)がTREC,KRECの発現パターンにより4群に分けられ、自己免疫疾患、悪性腫瘍の発生などの合併症の発生頻度、重症度と相関することを示した。
また原発性免疫不全症のデータベース(Primary Immunodeficiency Database in Japan,PIDJ)を構築した。
PIDJを利用し、樹状細胞欠損症が28名存在することを見出し、Exome解析により、患者全エクソンの遺伝子配列を次世代シークエンサーで解読し変異を解析した。その結果6人で樹状細胞欠損症の原因遺伝が転写因子GATA2の異常であることを新規に見出した。さらに、患者T細胞はIL-4,IL-17産生が著明に低下していて、Th2,Th17細胞への分化にGATA2が必須であること、また、T細胞新生能のマーカーであるTRECが、解析可能であった4患者全員で低下し、T細胞の初期分化にGATA2が重要な役割を果たしていることを示した。以上、免疫系で自己認識に深く関与する抗原提示において重要な役割を果たしている樹状細胞が欠損している疾患を見出し、その原因遺伝子を同定した。

Report

(2 results)
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (43 results)

All 2012 2011 2010 Other

All Journal Article (41 results) (of which Peer Reviewed: 41 results) Remarks (2 results)

  • [Journal Article] Hyper-eosinophilia granular acute B-cell lymphoblastic leukemia with myeloid antigen expression2012

    • Author(s)
      Kobayashi D, Kogawa K, Imai K, Tanaka T, Sada A, Nonoyama S
    • Journal Title

      Pediatr Int

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and genetic characteristics of XIAP deficiency in Japan2012

    • Author(s)
      Yang X, Kanegane H, Nishida N, Imamura T, Hamamoto K, Miyashita R, Imai K, Nonoyama S, Sanayama K, Yamaide A, Kato F, Nagai K, Ishii E, Zelm M, Latour S, Zhao X, Miyawaki T
    • Journal Title

      J Clin Immunol

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional STAT3 deficiency compromises IL-12-dependent generation of human T-follicular helper cells2012

    • Author(s)
      Ma CS, Avery DT, Chan A, Batten M, Bustamante J, Boisson-Dupuis S, Arkwright PD, Minegishi Y, Nonoyama S, French MA, Choo S, Peake J, Wong M, Cook MC, Fulcher DA, Casanova JL, Deenick EK, Tangye SG
    • Journal Title

      Blood

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils2012

    • Author(s)
      Honda F, Kano H, Kanegane H, Nonoyama S, Kim ES, Lee SK, Takagi M, Mizutani S, Morio T
    • Journal Title

      Nat Immunol

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Missense Mutations of the BMPR1B (ALK6) Gene in Childhood Idiopathic Pulmonary Arterial Hypertension2012

    • Author(s)
      Chida A, Shintani M, Nakayama T, Furutani Y, Hayama E, Inai K, Saji T, Nonoyama S, Nakanishi T
    • Journal Title

      Circ J

    • NAID

      10030316588

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GATA-2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B- and NK-cell (DCML) deficiency, and myelodysplasia2012

    • Author(s)
      Ishida H, Imai K, Homma K, Tamura S, Imamura T, Itoh M, Nonoyama S
    • Journal Title

      Eur J Pediatr

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical profile and genetic basis of Wiskott-Aldrich syndrome at Chandigarh, north India2012

    • Author(s)
      Suri D, Singh S, Rawat A, Gupta A, Kamae C, Honma K, Nakagawa N, Imai K, Nonoyama S, Oshima K, Mitsuiki N, Ohara O, Bilhou-Nabera C, Proust A, Ahluwalia J, Dogra S, Saikia B, Walker Minz R, Sehgal S
    • Journal Title

      Asian Pac J Allergy Immunol

      Volume: 30 Pages: 1-8

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Factors Associated with Steroid Phobia in Caregivers of Children with Atopic Dermatitis2012

    • Author(s)
      Kojima R, Fujiwara T, Matsuda A, Narita M, Matsubara O, Nonoyama S, Ohya Y, Saito H, Matsumoto K
    • Journal Title

      Pediatr Dermatol

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endocrine complications in primary immunodeficiency diseases in Japan2012

    • Author(s)
      Nozaki T, Takada H, Ishimura M, Ihara K, Imai K, Morio T, Kobayashi M, Nonoyama S, Hara T
    • Journal Title

      Clin Endocrinol

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Survey of Japanese infants younger than 3 months who were treated with oseltamivir for influenza : Safety of oseltamivir treatment2012

    • Author(s)
      Morioka I, Nonoyama S, Tanaka-Taya K, Ihara T, Sugaya N, Ueta I, Kumagai T, Okada K, Hosoya M, Okabe N, Morishima T
    • Journal Title

      Scand J Infect Dis

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple reversions of an IL2RG mutation restore T cell function in an X-linked severe combined immunodeficiency patient2012

    • Author(s)
      Kawai T, Saito M, Nishikomori R, Yasumi T, Izawa K, Murakami T, Okamoto S, Mori Y, Nakagawa N, Imai K, Nonoyama S, Wada T, Yachie A, Ohmori K, Nakahata T, Heike T
    • Journal Title

      J Clin Immunol

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Outcomes of Childhood Pulmonary Arterial Hypertension in BMPR2 and ALK1 Mutation Carriers2012

    • Author(s)
      Chida A, Shintani M, Yagi H, Fujiwara M, Kojima Y, Sato H, Imamura S, Yokozawa M, Onodera N, Horigome H, Kobayashi T, Hatai Y, Nakayama T, Fukushima H, Nishiyama M, Doi S, Ono Y, Yasukouchi S, Ichida F, Fujimoto K, Ohtsuki S, Teshima H, Kawano T, Nomura Y, Gu H, Ishiwata T, Furutani Y, Inai K, Saji T, Matsuoka R, Nonoyama S, Nakanishi T
    • Journal Title

      Am J Cardiol

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early and rapid detection of X-linked lymphoproliferative syndrome with SH2D1A mutations by flow cytometry2011

    • Author(s)
      Zhao M, Kanegane H, Kobayashi C, Nakazawa Y, Ishii E, Kasai M, Terui K, Gocho Y, Imai K, Kiyasu J, Nonoyama S, Miyawaki T
    • Journal Title

      Cytometry B Clin Cytom

      Volume: 80 Pages: 8-13

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of Sarcoplasmic Reticulum Ca2+Release and Ca2+ Transporters on Sarcolemmal Channels to Ca2+ Transient in Fetal Mouse Heart2011

    • Author(s)
      Takizawa M, Ishiwata T, Kawamura Y, Kanai T, Kurokawa T, Nishiyama M, Ishida H, Asano Y, Nonoyama S
    • Journal Title

      Pediatr Res

      Volume: 69 Pages: 306-311

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells2011

    • Author(s)
      Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Nonoyama S, Karasuyama H, Minegishi Y
    • Journal Title

      J Exp Med

      Volume: 208 Pages: 235-249

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantification of κ-deleting recombination excision circles in Guthrie cards for the identification of early B-cell maturation defects2011

    • Author(s)
      Nakagawa N, Imai K, Kanegane H, Sato H, Yamada M, Kondoh K, Okada S, Kobayashi M, Agematsu K, Takada H, Mitsuiki N, Oshima K, Ohara O, Suri D, Rawat A, Singh S, Pan-Hammarstrom Q, Hammarstrom L, Reichenbach J, Seger R, Ariga T, Hara T, Miyawaki T, Nonoyama S
    • Journal Title

      J Allergy Clin Immunol

      Volume: 128 Pages: 223-225

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Severe human herpesvirus 6 associated encephalopathy in three children : Analysis of cytokine profiles and the carnitine palmitoyltransferase 2 gene2011

    • Author(s)
      Matsumoto H, Hatanaka D, Ogura Y, Chida A, Nakamura Y, Nonoyama S
    • Journal Title

      Pediatr Infect Dis J

      Volume: 30 Pages: 999-1001

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nationwide Survey of Patients with Primary Immunodeficiency Diseases in Japan2011

    • Author(s)
      Ishimura M, Takada H, Doi T, Imai K, Sasahara Y, Kanegane H, Nishikomori R, Morio T, Heike T, Kobayashi M, Ariga T, Tsuchiya S, Nonoyama S, Miyawaki T, Hara T
    • Journal Title

      J Clin Immunol

      Volume: 31 Pages: 968-976

    • NAID

      120005133089

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Primary Immunodeficiency Diseases : an update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency2011

    • Author(s)
      Al-Herz W, Bousfiha A, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, Etzioni A, Fischer A, Franco JL, Geha RS, Hammarstrom L, Nonoyama S, Notarangelo LD, Ochs HD, Puck JM, Roifman C, Seger R, Tang MLK
    • Journal Title

      Front Immun

      Volume: 2 Pages: 54-54

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantification of human herpesvirus-6 (HHV-6) DNA in a cord blood transplant recipient with chromosomal integration of HHV-62011

    • Author(s)
      Kobayashi D, Kogawa K, Imai K, Tanaka T, Hiroi S, Satoh H, Tanaka-Taya K, Nonoyama S
    • Journal Title

      Transpl Infect Dis

      Volume: 13 Pages: 650-653

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ulinastatin, a Urinary Trypsin Inhibitor, for the Initial Treatment of Patients with Kawasaki2011

    • Author(s)
      Kanai T, Ishiwata T, Kobayashi T, Sato H, Takizawa M, Kawamura Y, Tsujimoto H, Nakatani K, Ishibashi N, Nishiyama M, Hatai Y, Asano Y, Kobayashi T, Takeshita S, Nonoyama S
    • Journal Title

      Circulation

      Volume: 124 Pages: 2822-2828

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiopulmonary arrest caused by craniometaphyseal dysplasia2011

    • Author(s)
      Chida A, Yanagawa Y, Matsumoto H, Nonoyama S
    • Journal Title

      Indian J Pediatr

      Volume: 78 Pages: 1010-1012

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of mutations and recombination activity in RAG-deficient patients2011

    • Author(s)
      Asai E, Wada T, Sakakibara Y, Toga A, Toma T, Shimizu T, Nampoothiri S, Imai K, Nonoyama S, Morio T, Muramatsu H, Kamachi Y, Ohara O, Yachie A
    • Journal Title

      Clin Immunol

      Volume: 138 Pages: 172-177

    • NAID

      120002772030

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid diagnosis of FHL3 by flow cytometric detection of intraplatelet Munc13-4 protein2011

    • 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 Pages: 1225-1230

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and host genetic characteristics of Mendelian susceptibility to mycobacterial diseases in Japan2011

    • Author(s)
      Hoshina T, Takada H, Sasaki-Mihara Y, Kusuhara K, Oshima K, Okada S, Kobayashi M, Ohara O, Hara T
    • Journal Title

      J Clin Immunol

      Volume: 31 Pages: 309-314

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel serum-free monolayer culture for orderly hematopoietic differentiation of human pluripotent cells via mesodermal progenitors2011

    • Author(s)
      Niwa A, Heike T, Umeda K, Oshima K, Kato I, Sakai H, Suemori H, Nakahata T, Saito MK.Jul
    • Journal Title

      PLoS One

      Volume: 6

    • NAID

      120003324603

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome2011

    • Author(s)
      Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, Nishikomori R, Morimoto T, Kambe N, Goldbach-Mansky R, Aksentijevich I, de Saint Basile G, Neven B, van Gijn M, Frenkel J, Arostegui JI, Yague J, Merino R, Ibanez M, Pontillo A, Takada H, Imagawa T
    • Journal Title

      Arthritis Rheum

      Volume: 63 Issue: 11 Pages: 3625-32

    • DOI

      10.1002/art.30512

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel mutations of MVK gene in Japanese family members affected with hyperimmunoglobulinemia D and periodic fever syndrome2011

    • Author(s)
      Mizuno T, Sakai H, Nishikomori R, Oshima K, Ohara O, Hata I, Shigematsu Y, Ishige T, Tamura K, Arakawa H
    • Journal Title

      Rheumatol Interest

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early and rapid detection of X-linked lymphoproliferative syndrome with SH2D1A mutations by flow cytometry.2011

    • Author(s)
      Zhao M, Kanegane H, Kobayashi C, Nonoyama S, et al.
    • Journal Title

      Cytometry Part B Clinical Cytometry

      Volume: 80(1) Pages: 8-13

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of mutations and recombination activity in RAG-deficient patients.2011

    • Author(s)
      Asai E, Wada T, Sakakibara Y, Nonoyama S, et al.
    • Journal Title

      Clinical Immunology

      Volume: 138(2) Pages: 172-7

    • NAID

      120002772030

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of sarcoplasmic reticulum Ca^2+release and Ca^2+transporters on sarcolemmal channels to Ca^2+transient in fetal mouse heart.ouse heart.2011

    • Author(s)
      Takizawa M, Ishiwata T, Kawamura Y, Nonoyama S., et al.
    • Journal Title

      Pediatric Research

      Volume: 69(4) Pages: 306-11

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells.2011

    • Author(s)
      Saito M, Nagasawa M, Takada H, Nonoyama S, et al.
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 208(2) Pages: 235-49

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantification of κ-deleting recombination excision circles in Guthrie cards for the identification of early B-cell maturation defects.2011

    • Author(s)
      Nakagawa N, Imai K, Kanegane H, Nonoyama S., et al.
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hemophagocytosis after bone marrow transplantation for JAK3-deficient severe combined immunodeficiency.2010

    • Author(s)
      Hashii Y, Yoshida H, Kuroda S, Nonoyama S, et al.
    • Journal Title

      Pediatric Transplantation

      Volume: 14(8)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of glycogen storage disease type Ib presenting with prolonged neonatal hypoglycaemia and minimal metabolic abnormalities.2010

    • Author(s)
      Matsumoto H, Kajiwara S, Ogura Y, Asano T, Horikawa R, Nonoyama S.
    • Journal Title

      Acta Paediatrica

      Volume: 99(2) Pages: 163-4

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia.2010

    • Author(s)
      Matsuda K, Sakashita K, Taira C, Nonoyama S, et al.
    • Journal Title

      British Journal of Haematology

      Volume: 148(4) Pages: 593-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] X-linked thrombocytopenia (XLT) due to WAS mutations : clinical characteristics, long-term outcome, and treatment options.2010

    • Author(s)
      Albert MH, Bittner TC, Nonoyama S, et al.
    • Journal Title

      Blood

      Volume: 115(16) Pages: 3231-8

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fetal and neonatal development of Ca^2+transients and functional sarcoplasmic reticulum in beating mouse hearts.2010

    • Author(s)
      Kawamura Y, Ishiwata T, Takizawa M, Ishida H, Asano Y, Nonoyama S.
    • Journal Title

      Circulation Journal

      Volume: 74(7) Pages: 1442-50

    • NAID

      10030695829

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyper IgM syndrome and complement Clq deficiency in an individual with systemic lupus erythematosus-like disease.2010

    • Author(s)
      Tsuge I, Kondo Y, Nakajima Y, Nonoyama S, et al.
    • Journal Title

      Clinical and Experimental Rheumatology

      Volume: 28(4) Pages: 558-60

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ataxia-telangiectasia in a patient presenting with hyper-immunoglobulin Msyndrome.2010

    • Author(s)
      Aghamohammadi A, Imai K, Moazzami K, Nonoyama S, et al.
    • Journal Title

      Journal of Investigational Allergology and Clinical Immunology

      Volume: 20(5) Pages: 442-5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency.2010

    • Author(s)
      Picard C, von Bernuth H, Ghandil P, Nonoyama S, et al.
    • Journal Title

      Medicine (Baltimore)

      Volume: 89(6) Pages: 403-25

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Remarks]

    • URL

      http://pidj.rcai.riken.jp/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://pidj.rcai.riken.jp/

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi