Research for developing of a screening method for the congenital immunodeficiency by KREC/TREC to apply the method to the pathologic analysis

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390213
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Defense Medical College
• Principal Investigator: NONOYAMA Shigeaki 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): OHARA Osamu 公益財団法人かずさDNA研究所, ヒトゲノム研究部, 副所長 (20370926) ; OSHIMA Koichi 京都大学, 学内共同利用施設等, 研究員 (60525377) ; IMAI Kohsuke 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (90332626)
• Project Period (FY): 2010 – 2012
• Keywords: 小児免疫・アレルギー・膠原病学 / 免疫学 / 遺伝子 / 移植・再生医療 / 発生・分化 / 感染症

Research Abstract

We developed real-time PCR-based quantification of T cell receptor excision circles (TREC) and signal joint Ig kappa-deleting recombination excision circles (KREC). We demonstrated that TREC and KREC measurement can be used for mass screening of severe combined immunodeficiency (SCID) and B lymphocyte deficiency in neonates. We also found that TREC and KREC can be used for classifying clinically diagnosed CVID patients into four groups, and that the clinical manifestations, prognosis and outcome are significantly different in these groups, indicating TREC/KREC are good clinical markers.

Research Products

• [Journal Article] Neonatal herpes encephalitis caused by a virologically confirmed acyclovir resistant herpes simplex virus type 1 (2013)
  • Author(s): Kakiuchi S, Nonoyama S, Wakamatsu H, Kogawa K, Wang L, Kinoshita-Yamaguchi H, Takayama-Ito M, Lim CK, Inoue N, Mizuguchi M, Igarashi T, Saijo M
  • Journal Title: J. Clin. Microbiol Volume: 51 Pages: 356-9
  • DOI: doi: 10.1128/JCM.02247-12.
• [Journal Article] Functional STAT3 deficiency compromises the generation of human T follicular helper cells (2012)
  • 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 Volume: 26 Pages: 119:3997-4008
  • DOI: doi: 10.1182/blood-2011-11-392985.
• [Journal Article] The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils (2012)
  • Author(s): Honda F, Kano H, Kanegane H, Nonoyama S, Kim ES, Lee SK, Takagi M, Mizutani S, Morio T
  • Journal Title: Nat Immunol Volume: 26 Pages: 369-378
  • DOI: doi: 10.1038/ni.2234.
• [Journal Article] GATA-2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B- and NK-cell (DCML) deficiency, and myelodysplasia (2012)
  • Author(s): Ishida H, Imai K, Homma K, Tamura S, Imamura T, Itoh M, Nonoyama S
  • Journal Title: Eur J Pediatr Volume: 171 Pages: 1273-1276
  • DOI: doi: 10.1007/s00431-012-1715-7.
• [Journal Article] Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery (2012)
  • Author(s): Takayuki Tanaka, Kazutoshi Takahashi, Mayu Yamane, Shota Tomida, Saori Nakamura, Koichi Oshima, Akira Niwa, Ryuta Nishikomori, Naotomo Kambe, Hideki Hara, Masao Mitsuyama, Nobuhiro Morone, John E. Heuser, Takuya Yamamoto, Akira Watanabe, Akiko Sato-Otsubo, Seishi Ogawa, Isao Asaka, Toshio Heike, Shinya Yamanaka, Tatsutoshi Nakahata, Megumu K. Saito
  • Journal Title: Blood Volume: 9;120(6) Pages: 1299-308
  • DOI: doi: 10.1007/s00431-012-1715-7.
• [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, 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
  • DOI: doi:10.1084/jem.20100799.
• [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, 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
  • DOI: doi: 10.1016/j.jaci.2011.01.052.
• [Journal Article] Nationwide Survey of Patients with Primary Immunodeficiency Diseases in Japan (2011)
  • Author(s): Ishimura M, Takada H, Doi T, Imai K, Sasahara Y, Kanegane H, Nishikomori R, 図4 ATM,NBS, Mre11患者のTREC /KREC定量 Morio T, Heike T, Kobayashi M, Ariga T, Tsuchiya S, Nonoyama S, Miyawaki T, Hara T
  • Journal Title: J Clin Immunol Volume: 31 Pages: 968-76
  • DOI: doi: 10.1007/s10875-011-9594-7.
• [Journal Article] Primary Immunodeficiency Diseases: an update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency (2011)
  • 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
  • DOI: doi: 10.3389/fimmu.2011.00054.
• [Journal Article] Analysis of mutations and recombination activity in RAG-deficient patients (2011)
  • 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: 172-7
  • DOI: doi: 10.1016/j.clim.2010.11.005.
• [Journal Article] Rapid diagnosis of FHL3 by flow cytometric detection of intraplatelet Munc13-4 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(5) Pages: 1225-30
  • DOI: doi: 10.1182/blood-2011-01-329540.
• [Journal Article] A novel serum-free monolayer culture for orderly hematopoietic differentiation of human pluripotent cells via mesodermal progenitors (2011)
  • Author(s): Niwa A, Heike T, Umeda K, Oshima K, Kato I, Sakai H, Suemori H, Nakahata T, Saito MK
  • Journal Title: PLoS One Volume: 6(7) Pages: e22261
  • DOI: doi: 10.1371/journal.pone.0022261.
• [Journal Article] ADA-SCID with 'WAZA-ARI' mutations that synergistically abolished ADA protein stability (2011)
  • Author(s): Okura Y, Yamada M, Kobayashi I, Santisteban I, Arredondo-Santisteban G, Kato Z, Iguchi A, Yoshida M, Ohara O, Nakagawa N, Imai K, Hershfield MS, Ariga T
  • Journal Title: Br J Haematol Volume: 153(5) Pages: 675-6
  • DOI: doi: 10.1111/j.1365-2141.2011.08640.x.
• [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, Notarangelo LD, Burns S, Imai K, Espanol T, Fasth A, Pellier I, Strauss G, MorioT ,Gathmann B, Noordzij JG, Fillat C, Hoenig M, Nathrath M, Meindl A, Pagel P, Wintergerst U, Fischer A, Thrasher AJ, Belohradsky BH, Ochs HD
  • Journal Title: Blood Volume: 115 Pages: 3231-3238
  • DOI: doi: 10.1182/blood-2009-09-239087.
• [Presentation] Clinical features and immunological abnormalities of GATA2 deficiency in JAPAN (2012)
  • Author(s): Honma K, Imai K, Kamae C, Ishida H, Ito Y, Kojima S, Yokosuka T, Kanegane H, Morio T, Sasahara Y, Fujiwara T, Harigae H, Hashii Y, Ohara O, Nonoyama S
  • Organizer: 15th Biennial Meeting of the European Society of Immunodeficiencies (ESID2012)
  • Place of Presentation: Florence, Italy
  • Year and Date: 20121000
• [Presentation] Classification of common variable immunodeficiency by quantification of T cell receptor recombination excision circles (TREC) and Ig kappa-deleting recombination excision circles (KREC) (2012)
  • Author(s): Kamae C, Nakagawa N, Sato H, Honma K, Mitsuiki N, Ohara O, Kanegane H, Pasic S, Pan-Hammarstrom Q, MC van Zelm, Morio T, Imai K, Nonoyama S
  • Organizer: 15th Biennial Meeting of the European Society of Immunodeficiencies (ESID2012)
  • Place of Presentation: Florence, Italy
  • Year and Date: 20121000
• [Presentation] Genetic analysis for 207 cases with primary immunodeficiency (PID) consulted to a single center through PID network in Japan (PIDJ) in 5 years (2007-2011) (2012)
  • Author(s): Mitsuiki N, Oshima K, Imai K, Ohara O, Morio T, Mizutani S
  • Organizer: 15th Biennial Meeting of the European Society of Immunodeficiencies (ESID2012)
  • Place of Presentation: Florence, Italy
  • Year and Date: 20121000
• [Presentation] 次世代シークエンサーにより、原因遺伝子の同定に至ったCVIDの1例 (2012)
  • Author(s): 釜江智佳子、満生紀子、小原明、野口恵美子、久保田健夫、本間健一、小原收、今井耕輔、野々山恵章
  • Organizer: 第3回関東甲越免疫不全症研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-09-22
• [Remarks]
  • URL: http://pidj.rcai.riken.jp/