Research on molecular mechanisms of break in immunological tolerance in disorders caused by single-gene defect
Project/Area Number |
23390270
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
MORIO Tomohiro 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (30239628)
|
Co-Investigator(Kenkyū-buntansha) |
OHARA Osamu かずさDNA研究所, ヒトゲノム研究部, 副所長 (20370926)
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Project Period (FY) |
2011-04-01 – 2014-03-31
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
|
Keywords | 分類不能免疫不全症 / 自己免疫疾患 / 免疫学的寛容 / レパートリー解析 / 責任遺伝子探索 / 次世代シークエンサー / 分類不能型免疫不全症 |
Research Abstract |
We set up a multiparameter flow cytometry for detailed immunophenotyping and KRECs/TRECs analysis for assessment of B and T cell neogenesis, respectively in order to delve into pathogenesis of autoimmunity developed in primary immunodeficiency (PID). We categorized the PID patients into several groups and also established a database for PID with autoimmunity. We developed an extensive method to analyze IgH and TCR repertoires using high-throughput next generation sequencing (NGS), and started measuring the repertoire in 10 patients. Through whole exome analysis (WEA) for more than 40 PID patients with autoimmunity, we identified a mutation in 5 patients. These include BTK, FANCA, LRBA, PIK3CD, and STAT1. Candidate genes (ranging one to six) were obtained by carrying out WEA for a patient and his/her family members in 5 patients.
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Report
(4 results)
Research Products
(78 results)
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[Journal Article] Simple diagnosis of STAT1 gain-of-function alleles in patients with chronic mucocutaneous candidiasis.2014
Author(s)
Mizoguchi Y, Tsumura M, Okada S, Hirata O, Minegishi S, Imai K, Hyakuna N, Muramatsu H, Kojima S, Ozaki Y, Imai T, Takeda S, Okazaki T, Ito T, Yasunaga S, Takihara Y, Bryant VL, Kong XF, Cypowyj S, Boisson-Dupuis S, Puel A, Casanova JL, Morio T, Kobayashi M.
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Journal Title
J. Leukoc. Biol.
Volume: 95
Pages: 667-76
DOI
Related Report
Peer Reviewed
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[Journal Article] Rapid Detection of Intracellular p47phox and p67phox by Flow Cytometry; Useful Screening T ests for Chronic Granulomatous Disease2013
Author(s)
Wada T, Muraoka M, T oma T, Imai T, Shigemura T, Agematsu K, Haraguchi K, Moriuchi H, Oh-Ishi T, Kitoh T, Ohara O, Morio T, Yachie A
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Journal Title
J Clin Immunol
Volume: 33
Pages: 857-864
Related Report
Peer Reviewed
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[Journal Article] Calssification of common variable immunodeficiency by quantification of T cell receptor and Ig kappa-deleting recombination excision circles2013
Author(s)
Kamae C, Nakagawa N, Sato H, Honma K, Mitsuiki N, Ohar a O. Kanegane H, Pasic S, Pan-Hammerstrom Q, van Zelm MC, Morio T, Imai K, Nonoyama S
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Journal Title
J Allergy Clin Immunol
Volume: 131
Pages: 1437-1440
Related Report
Peer Reviewed
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[Journal Article] A novel Wiskott-Aldrich syndrome protein mutation in an infant with thrombotic thrombocytopenic purpura2013
Author(s)
Kawasaki Y, T oyoda H, Otsuki S, Iwasa T, Iwamoto S, Azuma E, Itoh-Habe N, Wada H, Fujimura Y, Mor io T, Imai K, Mistusiki N, Ohara O, Komada Y
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Journal Title
Eur J Haematol
Volume: 290
Pages: 164-8
Related Report
Peer Reviewed
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[Journal Article] Artemis-dependent DNA double-strand break formation at stalled replication forks.2013
Author(s)
Unno J, Takagi M, Piao J, Sugimoto M, Honda F, Maeda D, Masutani M, Kiyono T, Watanabe F, Morio T, Teraoka H, Mizutani S.
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Journal Title
Cancer Sci.
Volume: 104
Pages: 703-10
DOI
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Peer Reviewed
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[Journal Article] Wiskott–Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia.2013
Author(s)
Yoshimi A, Kamachi Y, Imai K, Watanabe N, Nakadate H, Kanazawa T, Ozono S, Kobayashi R, Yoshida M, Kobayashi C, Hama A, Muramatsu H, Sasahara Y, Jakob M, Morio T, Ehl S, Manabe A, Niemeyer C, Kojima S.
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Journal Title
Pediatr Blood Cancer.
Volume: 60
Pages: 836-41
DOI
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Peer Reviewed
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[Journal Article] Rapid Detection of Intracellular p47phox and p67phox by Flow Cytometry; Useful Screening Tests for Chronic Granulomatous Disease.2013
Author(s)
Wada T, Muraoka M, Toma T, Imai T, Shigemura T, Agematsu K, Haraguchi K, Moriuchi H, Oh-Ishi T, Kitoh T, Ohara O, Morio T, Yachie A.
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Journal Title
J Clin Immunol.
Volume: 33
Pages: 857-874
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel Wiskott-Aldrich syndrome protein mutation in an infant with thrombotic thrombocytopenic purpura.2013
Author(s)
Kawasaki Y, Toyoda H, Otsuki S, Iwasa T, Iwamoto S, Azuma E, Itoh-Habe N, Wada H, Fujimura Y, Morio T, Imai K, Mitsuiki N, Ohara O, Komada Y.
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Journal Title
Eur J Haematol.
Volume: 290
Pages: 164-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: report of two Japanese patients without human immunodeficiency virus infection.2013
Author(s)
Kobayashi Z, Akaza M, Numasawa Y, Ishihara S, Tomimitsu H, Nakamichi K, Saijo M, Morio T, Shimizu N, Sanjo N, Shintani S, Mizusawa H.
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Journal Title
J Neurol Sci.
Volume: 15
Pages: 190-4
DOI
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Peer Reviewed
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[Journal Article] Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory2012
Author(s)
Kaji T, Ishige A, Hikida M, T aka J, Hijikata A, Kubo M, Nagashima T, T akahashi Y, Kurosaki T, Okada M, Ohar a O, Rajewsky K, T akemori T
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Journal Title
J Exp Med
Volume: 209
Pages: 2079-97
Related Report
Peer Reviewed
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[Journal Article] Detection of base substitution-type somatic mosaicism of the NLRP3 gene with >99.9% statistical confidence by massively parallel sequencing2012
Author(s)
Izawa K, Hijikata A, T anaka N, Kawai T, Saito MK, Goldbach-Mansky R, Aksentijevich I, Y asumi T, Nakahata T, Heike T, Nishikomori R, Ohar a O
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Journal Title
DNA Res
Volume: 19
Pages: 143-52
Related Report
Peer Reviewed
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[Journal Article] Process for immune defect and chromosomal translocation during early thymocyte development lacking ATM.2012
Author(s)
Isoda T, Takagi M, Piao J, Nishii R, Masaki S, Masuda K, Ikawa T, Azuma M, Morio T, Kawamoto H, Mizutani S.
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Journal Title
Blood.
Volume: 120
Pages: 789-99
DOI
Related Report
Peer Reviewed
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[Journal Article] Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia2012
Author(s)
Kuramitsu M, Sato-Otsubo A, Morio T, Takagi M, Toki T, Terui K, RuNan W, Kanno H, Ohga S, Ohara A, Kojima S, Kitoh T, Goi K, Kudo K, Matsubayashi T, Mizue N, Ozeki M, Masumi A, Momose H, Takizawa K, Mizukami T, Yamaguchi K, Ogawa S, Ito E
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Journal Title
Blood
Volume: 119
Pages: 2376-84
Related Report
Peer Reviewed
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[Journal Article] Impaired cell adhesion, apoptosis, and signaling in WASP-gene disrupted Nalm-6 pre-B cells and recovery of cell adhesion using a transducible form of WASp2012
Author(s)
Sato R, Iiizumi S, Kim E-S, Honda F, Lee S-K, Adachi N, Koyama H, Mizutani S, Morio T
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Journal Title
Int.J.Hematol.
Volume: 95
Pages: 299-310
Related Report
Peer Reviewed
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[Journal Article] Recurrent bacterial meningitis by three different pathogens in an isolated asplenic child2012
Author(s)
Uchida Y, Matsubara K, Wada T, Oishi K, Morio T, Takada H, Iwata A, Yura K, Kamimura K, Nigami H, Fukuya T
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Journal Title
J Infect Chemother
Volume: 52
Pages: 607-15
Related Report
Peer Reviewed
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[Journal Article] Nationwide Survey of Patients with Primary Immunodeficiency Diseases in Japan2011
Author(s)
Ishimura M, T akada H, Doi T, Imai K, Sasahara Y, Kanegane H, Nishikomori R, Mor io T, Heike T, Kobayashi M, Ariga T, T suchiya S, Nonoyama S, Miyawaki T, Hara T
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Journal Title
J Clin Immunol
Volume: 31
Pages: 968-76
Related Report
Peer Reviewed
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[Journal Article] Outcome of unrelated umbilical cord blood transplantation in 88patients with primary immunodeficiency in Japan2011
Author(s)
Mor io T, Atsuta Y, T omizawa D, Nagamura-Inoue T, Kato K, Ariga T, Kawa K, Koike K, T auchi H, Kajiwara M, Hara T, Kato S
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Journal Title
Br J Haematol
Volume: 154
Pages: 363-372
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Peer Reviewed
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[Journal Article] ADA-SCID with 'W AZA-ARI' mutations that synergistically abolished ADA protein stability2011
Author(s)
Okura Y, Y amada M, Kobayashi I, Santisteban I, Arredondo-Santisteban G, Kato Z, Iguchi A, Y oshida M, Ohar a O, Nakagawa N, Imai K, Hershfield MS, Ariga T
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Journal Title
Br J Haematol
Volume: 153
Pages: 675-6
Related Report
Peer Reviewed
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[Journal Article] Miyawaki T , Nonoyama S. Quantification of κ-deleting recombination excision circles in Guthrie cards for the identification of early B-cell maturation effects2011
Author(s)
Nakagawa N, Imai K, Kanegane H, Sato H, Y amada M, Kondoh K, Okada S, Kobayashi M, Agematsu K, T akada H, Mitsuiki N, Oshima K, Ohar a O, Suri D, Rawat A, Singh S, Nakagawa N, Imai K, Kanegane H, Sato H, Y amada M, Kondoh K, Okada S, Kobayashi M, Agematsu K, T akada H, Mitsuiki N, Oshima K, Ohar a O, Suri D, Rawat A, Singh S
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Journal Title
J Aller gy Clin I mmunol
Volume: 128
Pages: 223-225
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Peer Reviewed
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[Journal Article] Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells2011
Author(s)
Imadome K, Yajima M, Arai A, Nakazawa A, Kawano F, Ichikawa S, Shimizu N, Yamamoto N, Morio T, Ohga S, Nakamura H, Ito M, Miura O, Komano J, Fujiwara S
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Journal Title
Plos Pathogens.
Volume: 7
Pages: e1002326
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Peer Reviewed
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[Journal Article] Outcome of unrelated umbilical cord blood transplantation in 88patients with primary immunodeficiency in Japan2011
Author(s)
Morio T., Atsuta Y., Tomizawa D., Nagamura-Inoue T., Kato K., Ariga T., Kawa K., Koike K., Tauchi H., Kajiwara M., Hara T., Kato S.
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Journal Title
Br.J.Haematol.
Volume: 154
Pages: 363-372
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Peer Reviewed
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[Journal Article] Analysis of mutations and recombination activity in RAG-deficient patient2011
Author(s)
Asai E., Wada T., Sakakibara Y., Toga A., Toma T., Shimizu T., Imai K., Nonoyama S., Morio T., Kamachi Y., Ohara O., Yachie A.
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Journal Title
Clin.Immunol.
Volume: 138
Pages: 172-7
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Peer Reviewed
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[Journal Article] Autoimmune Lymphoproliferative Syndrome Like Disease With Somatic KRAS Mutation2011
Author(s)
Takagi M., Shinoda K., Piao J., Mitsuiki N., Takagi M., Matsuda K., Muramatsu H., Doisaki S., Nagasawa M., Morio T., Kasahara Y., Koike K., Kojima S., Takao A., MizutaniS.
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Journal Title
Blood
Volume: 117
Pages: 2887-9
Related Report
Peer Reviewed
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