Investigation of molecular mechanism and therapeutic target of Chronic Mucocutaneous Candidiasis

• Project/Area Number: 16H05355
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hiroshima University
• Principal Investigator: OKADA SATOSHI 広島大学, 医系科学研究科(医), 講師 (80457241)
• Co-Investigator(Kenkyū-buntansha): 津村 弥来 広島大学, 医歯薬保健学研究科(医), 研究員 (80646274) ; 山本 卓 広島大学, 理学研究科, 教授 (90244102)
• Research Collaborator: OHARA osamu ; ASANO takaki ; NISHIMURA shiho ; SAITO satoshi ; SAKATA sonoko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 慢性皮膚粘膜カンジダ症 / STAT1機能獲得型変異 / IL17RA / 造血細胞移植 / 疾患モデルマウス / STAT1 / 機能獲得型変異 / 原発性免疫不全症 / IL-17 / RORC / CMC / カンジダ / 全エクソーム解析

Outline of Final Research Achievements

We systematically investigated patients with gain-of-function (GOF) mutation in STAT1 that explain more than half of the patients with chronic mucocutaneous candidiasis (CMCD). We conducted questionnaire based international survey of patients with STAT1-GOF mutations and revealed that the patients show broad infectious and non-infectious manifestations. We next investigated patients with severe clinical manifestation who were treated with haematopoietic stem cell transplantation (HSCT). This study revealed that HSCT can be a curable treatment, but it has a significant risk of death. We also established reference database which can predict functional significance of uncharacterized amino acid substitution in STAT1. Simultaneously, we generated disease model mouse by generating R274Q STAT1-GOF mutation knock in mouse.
As for the CMCD patients without STAT1 mutation, we identified patients with IL17RA deficiency and characterized clinical manifestation of this disorder.

Academic Significance and Societal Importance of the Research Achievements

研究成果のうち学術的に意義深い点は以下の３点と考えられる。本研究により、1) STAT1遺伝子に認めたアミノ酸置換の病的意義が容易となった点、2) 本症の病態解明・治療法の開発に役立つ疾患モデルマウスを確立できた点、3) IL17RA異常症という疾患概念を確立できた点。
また本研究で、STAT1-GOF変異を持つ患者の臨床症状を明らかとするとともに、本症患者に対する造血幹細胞移植の有用性・問題点を解明することができた。この2点は、STAT1-GOF変異を持つ患者の診療に直結する成果であり、非常に大きな社会的意義を持つと考えらえる。

Research Products

• [Int'l Joint Research] Rockefeller University(米国)
• [Int'l Joint Research] Inserm/Necker Hospital for Sick Children(フランス)
• [Int'l Joint Research] Garvan Institute of Medical Research/Australian National University(オーストラリア)
• [Int'l Joint Research] University of Freiburg(ドイツ)
• [Int'l Joint Research] The Rockefeller University/University of South Florida/Johns Hopkins(United States)
• [Int'l Joint Research] Inserm/Imagine institute(France)
• [Int'l Joint Research] Garvan Institute of Medical Research(Australia)
• [Int'l Joint Research] Imperial College London(United Kingdom)
• [Int'l Joint Research] The Rockefeller University(United States)
• [Int'l Joint Research] Necker-Enfants Malades Hospital/INSERM(France)
• [Journal Article] Atypical SIFD with novel TRNT1 mutations: a case study on the pathogenesis of B-cell deficiency (2019)
  • Author(s): Kumaki E, Tanaka K, Imai K, Aoki-Nogami Y, Ishiguro A, Okada S, Kanegane H, Ishikawa F, Morio T.
  • Journal Title: International Journal of Hematology Volume: 109 Pages: 382-389
  • DOI: 10.1007/s12185-019-02614-0
  • Peer Reviewed
• [Journal Article] Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23 (2018)
  • Author(s): Martinez-Barricarte Ruben、Markle Janet G.、Ma Cindy S.、Deenick Elissa K.、Ramirez-Alejo Noe、 Mele Federico、Latorre Daniela、Mahdaviani Seyed Alireza、Aytekin Caner、Mansouri Davood、 Bryant Vanessa L.、Jabot-Hanin Fabienne、Deswarte Caroline、et al.
  • Journal Title: Science Immunology Volume: 3
  • DOI: 10.1126/sciimmunol.aau6759
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rescue of recurrent deep intronic mutation underlying cell type?dependent quantitative NEMO deficiency (2018)
  • Author(s): Boisson Bertrand、Honda Yoshitaka、Ajiro Masahiko、Bustamante Jacinta、Bendavid Matthieu、Gennery Andrew R.、Kawasaki Yuri、Ichishima Jose、Osawa Mitsujiro、Nihira Hiroshi、Shiba Takeshi、Tanaka Takayuki、Chrabieh Maya、Bigio Benedetta、Hur Hong、Itan Yuval、Liang Yupu、Okada Satoshi、et al.
  • Journal Title: Journal of Clinical Investigation Volume: 129 Pages: 583-597
  • DOI: 10.1172/jci124011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gain-of-function IKBKB mutation causes human combined immune deficiency. (2018)
  • Author(s): Cardinez C, Miraghazadeh B, Tanita K, da Silva E, Hoshino A, Okada S, Chand R, Asano T, Tsumura M, Yoshida K, Ohnishi H, Kato Z, Yamazaki M, Okuno Y, Miyano S, Kojima S, Ogawa S, Andrews TD, Field MA, Burgio G,et al.
  • Journal Title: J Exp Med. Volume: 215 Pages: 2715-2724
  • DOI: 10.1084/jem.20180639
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4?insufficient subjects (2018)
  • Author(s): Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, Wolff D, Hoshino A, Kobayashi M, Imai K, Takagi M, Dybedal I, Haddock JA, Sansom DM, Lucena JM, Seidl M, Schmitt-Graeff A, Reiser V, Emmerich F, Frede N, Bulashevska A, et al.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 142 Pages: 1932-1946
  • DOI: 10.1016/j.jaci.2018.02.055
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enhanced AKT phosphorylation of circulating B cells in patients with activated PI3Kδ syndrome. (2018)
  • Author(s): Asano Takaki、Okada Satoshi、Tsumura Miyuki、Yeh Tzu-Wen、Mitsui-Sekinaka Kanako、Tsujita Yuki、Ichinose Youjiro、Shimada Akira、Hashimoto Kunio、Wada Taizo、Imai Kohsuke、Ohara Osamu、Morio Tomohiro、Nonoyama Shigeaki、Kobayashi Masao
  • Journal Title: Front Immunol. Volume: 9 Pages: 568-568
  • DOI: 10.3389/fimmu.2018.00568
  • NAID: 120006473827
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers (2018)
  • Author(s): Egg David、Schwab Charlotte、Gabrysch Annemarie、Arkwright Peter D.、Cheesman Edmund、Giulino-Roth Lisa、Neth Olaf、Snapper Scott、Okada Satoshi、et al.
  • Journal Title: Frontiers in Immunology Volume: 9 Pages: 2012-2012
  • DOI: 10.3389/fimmu.2018.02012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mendelian susceptibility to mycobacterial disease: 2014-2018 update (2018)
  • Author(s): Rosain Jeremie、Kong Xiao-Fei、Martinez-Barricarte Ruben、Oleaga-Quintas Carmen、Ramirez-Alejo Noe、Markle Janet、Okada Satoshi、et al.
  • Journal Title: Immunology and Cell Biology Volume: epub
  • DOI: 10.1111/imcb.12210
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] コルチコステロイド減量により奇異性反応を繰り返した重症結核性髄膜炎・脳結核腫 (2018)
  • Author(s): 野間康輔, 土居岳彦, 古森遼太, 江口勇太, 小野大地, 松村梨紗, 望月慎史, 岡田 賢, 小林正夫
  • Journal Title: 小児科学会雑誌 Volume: 122(7) Pages: 1818-1825
  • Peer Reviewed
• [Journal Article] 慢性皮膚粘膜カンジダ症 (2018)
  • Author(s): 岡田 賢
  • Journal Title: 小児疾患の診断治療基準 Volume: 改訂5版 Pages: 266-267
  • NAID: 130005696887
• [Journal Article] メンデル遺伝型マイコバクテリア易感染症 (2018)
  • Author(s): 浅野孝基, 岡田 賢
  • Journal Title: 小児疾患の診断治療基準 改訂5版 Volume: 改訂5版 Pages: 264-265
• [Journal Article] 伴性遺伝性低ガンマグロブリン血症を伴うGH単独欠損症 (2018)
  • Author(s): 岡田 賢
  • Journal Title: 内分泌症候群（第3版）Iーその他の内分泌疾患を含めて－ Volume: （第3版）I Pages: 73-76
• [Journal Article] Hematopoietic stem cell transplantation in patients with Gain of Function STAT1 Mutation (2018)
  • Author(s): Leiding JW, Okada S, Hagin D, Abinun M, Shcherbina A, Balashov DN, Kim VHD, Ovadia A, Guthery SL, Pulsipher M, Lilic D, Devlin LA, Christie S, Depner M, Fuchs S, van Royen-Kerkhof A, et al.
  • Journal Title: J Allergy Clin Immunol Volume: 141 Pages: 704-717
  • DOI: 10.1016/j.jaci.2017.03.049
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection (2018)
  • Author(s): Zhang SY, Clark NE, Freije CA, Pauwels E, Taggart AJ, Okada S, Mandel H, Garcia P, Ciancanelli MJ, Biran A, Lafaille FG, Tsumura M, et al.
  • Journal Title: Cell. Volume: 172
  • DOI: 10.1016/j.cell.2018.02.019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Flow cytometry-based diagnosis of primary immunodeficiency diseases (2018)
  • Author(s): Kanegane H, Hoshino A, Okano T, Yasumi T, Wada T, Takada H, Okada S, Yamashita M, Yeh TW, Nishikomori R, Takagi M, Imai K, Ochs HD, Morio T.
  • Journal Title: Allergol. Int. Volume: 67 Issue: 1 Pages: 43-54
  • DOI: 10.1016/j.alit.2017.06.003
  • NAID: 130006322088
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants. (2017)
  • Author(s): Kagawa R, Fujiki R, Tsumura M, Sakata S, Nishimura S,Itan Y, Kong XF, Kato Z, Ohnishi H, Hirata O, Saito S, Ikeda M,Baghdadi JE, Bousfiha A, Fujiwara K, Oleastro M, Yancoski J,Perez L, Danielian S, Ailal F, Takada H, Hara T, Anne Puel A, Boisson-Dupuis S, Bustamante J, Casanova JL, Ohara O, Okada S, Masao Kobayashi M.
  • Journal Title: J Allergy Clin Immunol Volume: － Pages: 232-241
  • DOI: 10.1016/j.jaci.2016.09.035
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Abnormal hematopoiesis and autoimmunity in human subjects with germline IKZF1 mutations (2017)
  • Author(s): Hoshino A, Okada S, Yoshida K, Nishida N, Okuno Y, Ueno H, Yamashita M, Okano T, Tsumura M, Nishimura S, Sakata S, Kobayashi M, Nakamura H, Kamizono J, Mitsui-Sekinaka K, Ichimura T, Ohga S, Nakazawa Y, Takagi M, Imai K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Kojima S, Nonoyama S, Morio T, Kanegane H.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: - Pages: 223-231
  • DOI: 10.1016/j.jaci.2016.09.029
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular mechanism and structural basis of gain-of-function of STAT1 caused by pathogenic R274Q mutation (2017)
  • Author(s): Fujiki R, Hijikata A, Shirai T, Okada S, Kobayashi M, Ohara O
  • Journal Title: Journal of Biological Chemistry Volume: 292 Pages: 6240-6254
  • DOI: 10.1074/jbc.m116.753848
  • Peer Reviewed / Open Access
• [Journal Article] A gain-of-function mutation of STAT1: A novel genetic factor contributing to chronic mucocutaneous candidiasis (2017)
  • Author(s): Eslami Narges、Tavakol Marzieh、Mesdaghi Mehrnaz、Gharegozlou Mohammad、Casanova Jean-Laurent、Puel Anne、Okada Satoshi、Arshi Saba、Bemanian Mohammad Hassan、Fallahpour Morteza、Molatefi Rasool、Seif Farhad、Zoghi Samaneh、Rezaei Nima、Nabavi Mohammad
  • Journal Title: Acta Microbiol Immunol Hung Volume: 64 Pages: 191-201
  • DOI: 10.1556/030.64.2017.014
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Significant augmentation of regulatory T cell numbers occurs during the early neonatal period (2017)
  • Author(s): Hayakawa S.、Ohno N.、Okada S.、Kobayashi M.
  • Journal Title: Clin Exp Immunol. Volume: 190 Pages: 268-279
  • DOI: 10.1111/cei.13008
  • Peer Reviewed
• [Journal Article] Anti-human neutrophil antigen-1a, -1b, and -2 antibodies in neonates and children with immune neutropenias analyzed by extracted granulocyte antigen immunofluorescence assay (2017)
  • Author(s): Onodera Rie、Kurita Emi、Taniguchi Kikuyo、Karakawa Shuhei、Okada Satoshi、Kihara Hirotaka、Fujii Teruhisa、Kobayashi Masao
  • Journal Title: Transfusion Volume: 57 Pages: 2586-2594
  • DOI: 10.1111/trf.14291
  • Peer Reviewed
• [Journal Article] Individual Clinically Diagnosed with CHARGE Syndrome but with a Mutation in KMT2D, a Gene Associated with Kabuki Syndrome: A Case Report (2017)
  • Author(s): Sakata Sonoko、Okada Satoshi、Aoyama Kohei、Hara Keiichi、Tani Chihiro、Kagawa Reiko、Utsunomiya-Nakamura Akari、Miyagawa Shinichiro、Ogata Tsutomu、Mizuno Haruo、Kobayashi Masao
  • Journal Title: Front Genet. Volume: 8 Pages: 210-210
  • DOI: 10.3389/fgene.2017.00210
  • Peer Reviewed / Open Access
• [Journal Article] A Case with Spondyloenchondrodysplasia Treated with Growth Hormone (2017)
  • Author(s): Utsumi Takanori、Okada Satoshi、Izawa Kazushi、Honda Yoshitaka、Nishimura Gen、Nishikomori Ryuta、Okano Rika、Kobayashi Masao
  • Journal Title: Front Endocrinol. Volume: 8 Pages: 157-157
  • DOI: 10.3389/fendo.2017.00157
  • NAID: 120006331972
  • Peer Reviewed / Open Access
• [Journal Article] Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia: Results from a Japanese clinical trial (2017)
  • Author(s): Kitaoka Taichi、Tajima Toshihiro、Nagasaki Keisuke、Kikuchi Toru、Yamamoto Katsusuke、Michigami Toshimi、Okada Satoshi、Fujiwara Ikuma、Kokaji Masayuki、Mochizuki Hiroshi、Ogata Tsutomu、Tatebayashi Koji、Watanabe Atsushi、Yatsuga Shuichi、Kubota Takuo、Ozono Keiichi
  • Journal Title: Clin Endocrinol. Volume: 87 Pages: 10-19
  • DOI: 10.1111/cen.13343
  • Peer Reviewed
• [Journal Article] Newborn screening for carnitine palmitoyltransferase II deficiency using (C16+C18:1)/C2: Evaluation of additional indices for adequate sensitivity and lower false-positivity (2017)
  • Author(s): Tajima G, Hara K, Tsumura M, Kagawa R, Okada S, Sakura N, Maruyama S, Noguchi A, Awaya T, Ishige N, Musha I, Ajihara S, Ohtake A, Naito E, Hamada Y, Kono T, Asada T, Sasaio H, Fukaoo T, Fujikip R, Ohara O, Bo R, Yamada K, Kobayashi H, Hasegawa Y, Yamaguchi S, Takayanagis M, Hata I, Shigematsu Y, Kobayashi M
  • Journal Title: Mol Genet Metab. Volume: 122 Pages: 67-75
  • DOI: 10.1016/j.ymgme.2017.07.011
  • Peer Reviewed / Open Access
• [Journal Article] Characteristic clinical features of adipsic hypernatremia patients with subfornical organ-targeting antibody (2017)
  • Author(s): Nakamura-Utsunomiya A, Hiyama TY, Okada S, Noda M, Kobayashi M.
  • Journal Title: Clin Pediatr Endocrinol Volume: 26 Issue: 4 Pages: 197-205
  • DOI: 10.1297/cpe.26.197
  • NAID: 130006105714
  • ISSN: 0918-5739, 1347-7358
  • Peer Reviewed
• [Journal Article] Clinical characteristics of septo-optic dysplasia accompanied by congenital central hypothyroidism in Japan (2017)
  • Author(s): Nagasaki Keisuke、Kubota Takuo、Kobayashi Hironori、Sawada Hirotake、Numakura Chikahiko、Harada Shohei、Takasawa Kei、Minamitani Kanshi、Ishii Tomohiro、Okada Satoshi、Kamasaki Hotaka、Sugihara Shigetaka、Adachi Masanori、Tajima Toshihiro
  • Journal Title: Clin Pediatr Endocrinol Volume: 26 Issue: 4 Pages: 207-213
  • DOI: 10.1297/cpe.26.207
  • NAID: 130006105766
  • ISSN: 0918-5739, 1347-7358
  • Peer Reviewed
• [Journal Article] 慢性皮膚粘膜カンジダ症 (2017)
  • Author(s): 岡田 賢
  • Journal Title: 日本臨床免疫学会会誌 Volume: 40 Pages: 109-117
  • NAID: 130005696887
• [Journal Article] Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency. (2016)
  • Author(s): Levy R, Okada S, Beziat V, Moriya K, Liu C, Chai LY, Migaud M, Hauck F, Al Ali A, Cyrus C, Vatte C, Patiroglu T, Unal E, Ferneiny M, Hyakuna N, Nepesov S, Oleastro M, Ikinciogullari A, Dogu F, Asano T, et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 113
  • DOI: 10.1073/pnas.1618300114
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity. (2016)
  • Author(s): Okada S, Puel A, Casanova JL, Kobayashi M
  • Journal Title: Clin Transl Immunology. Volume: 5
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase δ syndrome-like immunodeficiency (2016)
  • Author(s): Tsujita Y, et al.
  • Journal Title: J Allergy Clin Immunol Volume: 138 Pages: 1672-1680
  • DOI: 10.1016/j.jaci.2016.03.055
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Unique and shared signaling pathways co-operate to regulate the differentiation of human CD4+T cells into distinct effector subsets. (2016)
  • Author(s): Ma CS, Wong N, Rao G, Nguyen A, Avery DT, Payne K, Torpy J, O'Young P, Deenick E, Bustamante J, Puel A, Okada S, Kobayashi M, Martinez-Barricarte R, Elliott M, Sebnem Kilic S, El Baghdadi J, Minegishi Y, Bousfiha A, Robertson N, et al.
  • Journal Title: J Exp Med Volume: 213 Pages: 1589-1608
  • DOI: 10.1084/jem.20151467
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype: an international survey of 274 patients from 167 kindreds. (2016)
  • Author(s): Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, Ouachee-Chardin M, Fouyssac F, Girisha KM, Etzioni A, Van Montfrans J, Camcioglu Y, Kerns LA, Belohradsky B, Blanche S, Bousfiha A, Rodriguez-Gallego C, Meyts I, Kisand K, Reichenbach J, et al.
  • Journal Title: blood. Volume: 127 Pages: 3154-3164
  • DOI: 10.1182/blood-2015-11-679902
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 原発性免疫不全症患者の分子学的診断 (2019)
  • Author(s): 岡田 賢
  • Organizer: 第2回日本免疫不全・自己炎症学会総会
  • Invited
• [Presentation] MSMD update (2018)
  • Author(s): 岡田 賢
  • Organizer: 第60回 日本小児血液・がん学会
  • Invited
• [Presentation] 未来を担う若手への『研究』のススメ (2018)
  • Author(s): 岡田 賢
  • Organizer: 第46回 日本臨床免疫学会総会
  • Invited
• [Presentation] HSCT in Patients with STAT1 Gain-of-function Mutation (2018)
  • Author(s): Satoshi Okada
  • Organizer: 2018 the Korean Society of Pediatric Hematology-Oncology Autumn Meeting
  • Int'l Joint Research / Invited
• [Presentation] STAT1 gain of function etiology, molecular biology, and treatment (2018)
  • Author(s): Satoshi Okada
  • Organizer: The 2nd APSID Scientific Congress
  • Int'l Joint Research / Invited
• [Presentation] STAT1機能獲得型変異による原発性免疫不全症患者に対する造血幹細胞移植の有効性と問題点の検討 (2018)
  • Author(s): 岡田 賢, Jennifer W. Leiding, Troy R. Torgerson, 今井耕輔, 井口晶裕, 有賀 正, 森尾友宏, 小林正夫
  • Organizer: 第40回 日本造血細胞移植学会総会
• [Presentation] STAT1機能獲得型変異による原発性免疫不全症 (2018)
  • Author(s): 岡田 賢
  • Organizer: 第1 回日本免疫不全・自己炎症学会総会・学術集会
  • Invited
• [Presentation] Asfotase Alfa投与によりミオパチー症状の軽快を得た成人型低ホスファターゼ症 (2017)
  • Author(s): 岡田 賢, 坂田園子, 香川礼子, 宇都宮朱里, 立川 加奈子, 北岡太一, 道上敏美, 大薗恵一, 小林正夫
  • Organizer: 第90回 日本内分泌学会学術集会
• [Presentation] Primary immunodeficiency associate with functional defect of RORγT (2016)
  • Author(s): Satoshi Okada, Janet Markle, Anne Puel, Masao Kobayashi, Jean-Laurent Casanova
  • Organizer: The 39th Annual Meeting of the Molecular Biology
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] International survey of clinical manifestations of patients with STAT1 gain-of-function mutations (2016)
  • Author(s): 岡田賢, 津村弥来, 西村志帆, 坂田園子, 香川礼子, Julie Toubiana, Anne Puel, Jean-Laurent Casanova, 小林正夫
  • Organizer: 第78回 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-13
• [Presentation] Alanine-scanning mutagenesis of human STAT1 to estimate the loss- or gain-of-function nature of variants (2016)
  • Author(s): Satoshi Okada, Ryoji Fujiki, Reiko Kagawa, Miyuki Tsumura, Xiaofei Kong, Sonoko Sakata, Shiho Nishimura, Zenichiro Kato, Hidenori Ohnishi, Yuval Itan, Stephanie Boisson-Dupuis, Jacinta Bustamante, Jean-Laurent Casanova, Osamu Ohara, and Masao Kobayashi
  • Organizer: 17th Biennial Meeting of the European Society for immunodeficiencies
  • Place of Presentation: Barcelona (Spain)
  • Year and Date: 2016-09-21
  • Int'l Joint Research
• [Presentation] STAT1機能獲得型変異を有する原発性免疫不全症患者の臨床症状の国際調査 (2016)
  • Author(s): 岡田賢, 津村弥来, 西村志帆, 坂田園子, Julie Toubiana, Anne Puel, Jean-Laurent Casanova, 小林正夫
  • Organizer: 第44回 日本臨床免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-08
• [Presentation] Loss-of-function and dominant negative STAT1 coiled-coil domain mutations in MSMD (2016)
  • Author(s): Satoshi Okada, Reiko Kagawa, Ryoji Fujiki, Zenichiro Kato, Hidenori Ohnishi, Stephanie Boisson-Dupuis, Jacinta Bustamante, Jean-Laurent Casanova, Osamu Ohara, and Masao Kobayashi
  • Organizer: Congress of Asia Pacific Society for Immunodeficiencies
  • Place of Presentation: Hong Kong (China)
  • Year and Date: 2016-04-30
  • Int'l Joint Research
• [Book] 原発性免疫不全症症候群 診療の手引き (2017)
  • Author(s): 岡田 賢
  • Total Pages: 10
  • Publisher: 診断と治療社
• [Book] 臨床免疫・アレルギー科 (2017)
  • Author(s): 岡田 賢, 津村弥来, 小林正夫
  • Total Pages: 7
  • Publisher: 科学評論社
• [Book] 日本臨床 免疫症候群III (2016)
  • Author(s): 岡田 賢
  • Total Pages: 17
  • Publisher: 日本臨牀社
• [Remarks] Identifying mutants one amino acid at a time
  • URL: https://www.nanbyo-research.jp/research/28/identifying-mutants-one-amino-acid-at-a-time
• [Remarks] Outcomes of stem cell transplants
  • URL: https://www.nanbyo-research.jp/research/31/outcomes-of-stem-cell-transplants-in-gene-mutation-patients
• [Remarks] 稀な免疫不全症、APDSの迅速診断法を開発
  • URL: https://www.amed.go.jp/news/release_20180405-02.html
• [Remarks] 稀な免疫不全症、APDSの迅速診断法を開発
  • URL: https://www.hiroshima-u.ac.jp/news/44718
• [Remarks] Rapid test pinpoints enzyme-related immuno def.
  • URL: https://www.nanbyo-research.jp/research/37/rapid-test-pinpoints-enzyme-related-immune-deficiency
• [Remarks] 【研究成果】まれな原発性免疫不全症に対する造血幹細胞移植の有効性と問題点を解明
  • URL: https://www.hiroshima-u.ac.jp/news/40053
• [Remarks] STAT1遺伝子変異の病的意義を高精度に予測するツール
  • URL: https://www.hiroshima-u.ac.jp/news/36849