Characterization of etiology of primary immunodeficiency by focusing on host susceptibility to specific pathogens

• Project/Area Number: 19H03620
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hiroshima University
• Principal Investigator: OKADA SATOSHI 広島大学, 医系科学研究科(医), 教授 (80457241)
• Co-Investigator(Kenkyū-buntansha): 小原 收 公益財団法人かずさDNA研究所, その他部局等, 副所長 (20370926) ; 津村 弥来 広島大学, 医系科学研究科(医), 研究員 (80646274)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 原発性免疫不全症 / メンデル遺伝型マイコバクテリア易感染症 / 慢性皮膚粘膜カンジダ症 / STAT1 / MSMD / CMC / 慢性皮膚粘膜カンジダ感染 / RORγT / IL-17RC / 多発性骨髄炎 / 脱リン酸化酵素 / 慢性皮膚粘膜カンジダ感染症 / CMCD

Outline of Research at the Start

抗酸菌に対して選択的に易感染性を示すMSMDと、カンジダに対して選択的に易感染性を示すCMCDを研究対象とする。未診断のMSMD、CMCD患者、および、MSMDとCMCDを合併した患者に対して全エクソーム解析、RNAシークエンスを併用した網羅的解析を行い、新規責任遺伝子を同定する。さらに、同定した遺伝子変異の病的意義を実験的に検証し、該当分子の障害による新規の原発性免疫不全症という疾患概念を確立する。並行して、リン酸化プロテオーム解析によって、CMCDの主要原因であるSTAT1機能獲得型（GOF）変異が細胞内リン酸化ネットワークへ及ぼす影響を明らかとする。

Outline of Final Research Achievements

We worked to identify the responsible genes in patients with primary immunodeficiency and to elucidate the molecular pathogenesis of the disease based on the identification of the responsible genes. As a representative result, we discovered RELA deficiency due to dominant negative effect. We have also worked extensively to elucidate the pathogenesis of STAT1 abnormalities, including the identification of the first autosomal recessive STAT1 complete deficiency in Japan, the elucidation of the epidemiology of autosomal dominant STAT1 partial deficiency, and the elucidation of the pathogenesis of STAT1 gain-of-function.

Academic Significance and Societal Importance of the Research Achievements

RELA異常症は半量不全で発症することが知られていたが、本研究での優性阻害効果により発症するRELA異常症の同定は、本症の疾患概念を変える発見であり、その学術的意義は極めて高い。抗NMDAR脳炎の乳児例におけるIRAK4欠損症の同定も、傍腫瘍症候群という側面が強かった抗NMDAR脳炎の病態を考える上で、非常に重要な知見となる。STAT1異常症の病態解明は、代表者が長年取り組んできた研究課題であり、診断確定により造血幹細胞移植による救命が得られた症例の存在など、社会的意義も高いと言える。

Research Products

• [Int'l Joint Research] ロックフェラー大学/ベイラー大学/ペンシルバニア大学(米国)
• [Int'l Joint Research] INSERM/ネッケル小児病院(フランス)
• [Int'l Joint Research] インペリアル大学(英国)
• [Int'l Joint Research] 復旦大學/長庚大學(中国)
• [Int'l Joint Research] Garvan Institute(オーストラリア)
• [Int'l Joint Research]
• [Int'l Joint Research] ロックフェラー大学/ベイラー大学/ペンシルバニア大学(米国)
• [Int'l Joint Research] INSERM/ネッケル小児病院(フランス)
• [Int'l Joint Research] インペリアル大学(英国)
• [Int'l Joint Research] 復旦大学/長庚大學(中国)
• [Journal Article] Mendelian susceptibility to mycobacterial diseases: state-of-the-art (2022)
  • Author(s): Noma Kosuke、Mizoguchi Yoko、Tsumura Miyuki、Okada Satoshi
  • Journal Title: Clinical Microbiology and Infection Volume: － Issue: 11 Pages: 00143-4
  • DOI: 10.1016/j.cmi.2022.03.004
  • Peer Reviewed / Open Access
• [Journal Article] Early diagnosis of partial interferon-γ receptor 1 deficiency prevents the development of Bacille de Calmette et Guerin osteomyelitis (2022)
  • Author(s): Tomomasa Dan、Tanita Kay、Higashi Seishi、Tasaka Yuri、Shimamura Takashi、Sakurai Urara、Matsubara Tomoyo、Okada Satoshi、Morio Tomohiro、Kanegane Hirokazu
  • Journal Title: Clinical Immunology Volume: 235 Pages: 108933-108933
  • DOI: 10.1016/j.clim.2022.108933
  • Peer Reviewed
• [Journal Article] Therapeutic options for CTLA-4 insufficiency (2022)
  • Author(s): Egg David、Rump Ina Caroline、Mitsuiki Noriko、Rojas-Restrepo Jessica、Maccari Maria-Elena、 Schwab Charlotte、Gabrysch Annemarie、Warnatz Klaus、Goldacker Sigune、Patino Virginia、Wolff Daniel、Okada Satoshi、et al.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 149 Issue: 2 Pages: 736-746
  • DOI: 10.1016/j.jaci.2021.04.039
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enhanced osteoclastogenesis in patients with MSMD due to impaired response to IFN-γ (2022)
  • Author(s): Tsumura Miyuki、Miki Mizuka、Mizoguchi Yoko、Hirata Osamu、Nishimura Shiho、Tamaura Moe、Kagawa Reiko、Hayakawa Seiichi、Kobayashi Masao、Okada Satoshi
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 149 Issue: 1 Pages: 252-261
  • DOI: 10.1016/j.jaci.2021.05.018
  • Peer Reviewed / Open Access
• [Journal Article] 自己炎症性疾患関連血管炎 (2022)
  • Author(s): 土居 岳彦, 野間 康輔, 岡田 賢
  • Journal Title: 日本免疫不全・自己炎症学会雑誌 Volume: 1 Pages: 3-12
  • NAID: 130008142176
• [Journal Article] Identification of discriminative gene-level and protein-level features associated with pathogenic gain-of-function and loss-of-function variants (2021)
  • Author(s): Sevim Bayrak Cigdem、Stein David、Jain Aayushee、Chaudhary Kumardeep、Nadkarni Girish N.、Van Vleck Tielman T.、Puel Anne、Boisson-Dupuis Stephanie、Okada Satoshi、Stenson Peter D.、Cooper David N.、Schlessinger Avner、Itan Yuval
  • Journal Title: The American Journal of Human Genetics Volume: 108 Issue: 12 Pages: 2301-2318
  • DOI: 10.1016/j.ajhg.2021.10.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association (2021)
  • Author(s): Martinot Martin、Korganow Anne Sophie、Wald Mathieu、Second Julie、Birckel Elodie、Mahe Antoine、Souply Laurent、Mohseni-Zadeh Mahsa、Droy Laure、Tarabeux Julien、Okada Satoshi、 Migaud Melanie、Puel Anne、Guffroy Aurelien
  • Journal Title: Frontiers in Immunology Volume: 12 Pages: 760019-760019
  • DOI: 10.3389/fimmu.2021.760019
  • Peer Reviewed / Open Access
• [Journal Article] Heterozygous missense variant of the proteasome subunit β-type 9 causes neonatal-onset autoinflammation and immunodeficiency (2021)
  • Author(s): Kanazawa N, Hemmi H, Kinjo N, Ohnishi H, Hamazaki J, M.H, K.A, M.T, H.S, K.N, K.S, H.Y, I.K, N.R, T.M, Y.Y, T.S, O.T, O.T, K.T, S.I, F.Y, W.N, I.Y, K.K, O.S, T.T, N.K, M.S, Y.K, Kaisho T
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 0-0
  • DOI: 10.1038/s41467-021-27085-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations (2021)
  • Author(s): Tomioka K, Miyamoto T, Akutsu SN, Yanagihara H, Fujita K, Royba E, Tauchi H, Yamamoto T, Koh I, Hirata E, Kudo Y, Kobayashi M, Okada S, Matsuura S
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 1-13
  • DOI: 10.1038/s41598-021-98673-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The expansion of human T-bet high CD21 low B cells is T cell dependent (2021)
  • Author(s): Keller Baerbel、Strohmeier Valentina、Harder Ina、Unger Susanne、Payne Kathryn J.、Andrieux Geoffroy、Boerries Melanie、Felixberger Peter Tobias、Landry Jonathan J. M.、Nieters Alexandra、Rensing-Ehl Anne、Salzer Ulrich、Frede Natalie、Usadel Susanne、Elling Roland、 Speckmann Carsten、...、Okada Satoshi、et al.
  • Journal Title: Science Immunology Volume: 6 Issue: 64
  • DOI: 10.1126/sciimmunol.abh0891
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inborn errors of STAT1 immunity (2021)
  • Author(s): Mizoguchi Yoko、Okada Satoshi
  • Journal Title: Current Opinion in Immunology Volume: 72 Pages: 59-64
  • DOI: 10.1016/j.coi.2021.02.009
  • Peer Reviewed
• [Journal Article] Novel STAT-3 gain-of-function variant with hypogammaglobulinemia and recurrent infection phenotype (2021)
  • Author(s): Melinda Erdos、Miyuki Tsumura、Judit Kallai、Arpad Lanyi、Zoltan Nyul、Gyorgy Balazs、Satoshi Okada、Laszlo Marodi
  • Journal Title: Clinical and Experimental Immunology Volume: 205 Issue: 3 Pages: 354-362
  • DOI: 10.1111/cei.13625
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths (2021)
  • Author(s): Paul Bastard、Adrian Gervais、Tom Le Voyer、Jeremie Rosain、Quentin Philippot、Jeremy Manry、 Eleftherios Michailidis、Hans-Heinrich Hoffmann、Shohei Eto、Marina Garcia-Prat 、Lucy Bizien、 Alba Parra-Martinez、Rui Yang、Liis Haljasmagi、Melanie Migaud、...、Satoshi Okada、et al.
  • Journal Title: Science Immunology Volume: 6 Issue: 62 Pages: 1-26
  • DOI: 10.1126/sciimmunol.abl4340
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS (2021)
  • Author(s): Yamashita Motoi、Kuehn Hye Sun、Okuyama Kazuki、Okada Satoshi、Inoue Yuzaburo、Takagi Masatoshi、Kanegane Hirokazu、Takeuchi Masahiro、Shimojo Naoki、Tsumura Miyuki、Padhi Aditya K.、Zhang Kam Y. J.、Boisson Bertrand、Casanova Jean-Laurent、Ohara Osamu、Rosenzweig Sergio D.、Taniuchi Ichiro、Morio Tomohiro
  • Journal Title: Nature Immunology Volume: 22 Issue: 7 Pages: 893-903
  • DOI: 10.1038/s41590-021-00951-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency (2021)
  • Author(s): Le Voyer Tom、Sakata Sonoko、Tsumura Miyuki、Khan Taushif、Esteve-Sole Ana、Al-Saud Bandar K.、 Gungor Hatice Eke、Taur Prasad、Jeanne-Julien Valentine、Christiansen Mette、Kohler Lisa- Maria、ElGhazali Gehad Eltayeb、Rosain Jeremie、Nishimura Shiho、Sakura Fumiaki、...、Okada Satoshi、Bustamante Jacinta
  • Journal Title: The Journal of Immunology Volume: 207 Issue: 1 Pages: 133-152
  • DOI: 10.4049/jimmunol.2001451
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 維持療法中にヒトパルボウイルスB19 感染による急激な貧血を伴う血球減少を呈した混合形質性急性白血病の一例 (2021)
  • Author(s): 芦原康介，松村梨紗，望月慎史，森下祐介，野間康輔，川口浩史，小林正夫，岡田 賢
  • Journal Title: 日本小児血液・がん学会雑誌 Volume: 58 Pages: 442-445
  • NAID: 130008158330
• [Journal Article] 好中球減少症（自己免疫性好中球減少症、重症先天性好中球減少症） (2021)
  • Author(s): 郷田 聡, 川口浩史, 岡田 賢
  • Journal Title: 小児内科 Volume: 53 Pages: 1094-1098
• [Journal Article] Inherited CARD9 Deficiency in a Child with Invasive Disease Due to Exophiala dermatitidis and Two Older but Asymptomatic Siblings (2021)
  • Author(s): Imanaka Yusuke、Taniguchi Maki、Doi Takehiko、Tsumura Miyuki、Nagaoka Rie、Shimomura Maiko、Asano Takaki、Kagawa Reiko、Mizoguchi Yoko、Karakawa Shuhei、Arihiro Koji、Imai Kohsuke、Morio Tomohiro、Casanova Jean-Laurent、Puel Anne、Ohara Osamu、Kamei Katsuhiko、Kobayashi Masao、Okada Satoshi
  • Journal Title: Journal of Clinical Immunology Volume: - Issue: 5 Pages: 975-986
  • DOI: 10.1007/s10875-021-00988-7
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Successful Hematopoietic Stem Cell Transplantation for Autosomal Recessive STAT1 Complete Deficiency (2021)
  • Author(s): Karakawa Shuhei、Shimomura Maiko、Sakata Sonoko、Matsubayashi Tadashi、Okada Satoshi
  • Journal Title: Journal of Clinical Immunology Volume: 41 Issue: 3 Pages: 684-687
  • DOI: 10.1007/s10875-020-00948-7
  • Peer Reviewed
• [Journal Article] Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation (2021)
  • Author(s): Beck David B.、Basar Mohammed A.、Asmar Anthony J.、Thompson Joyce J.、Oda Hirotsugu、Uehara Daniela T.、Saida Ken、Pajusalu Sander、Talvik Inga、D’Souza Precilla、Bodurtha Joann、Mu Weiyi、Baranano Kristin W.、Miyake Noriko、Wang Raymond、Kempers Marlies、Tamada Tomoko、Nishimura Yutaka、Okada Satoshi、et al.
  • Journal Title: Science Advances Volume: 7 Issue: 4
  • DOI: 10.1126/sciadv.abe2116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and Immunological Heterogeneity in Japanese Patients with Gain-of-Function Variants in STAT3 (2021)
  • Author(s): Tanita Kay、Sakura Fumiaki、Nambu Ryusuke、Tsumura Miyuki、Imanaka Yusuke、Ohnishi Hidenori、Kato Zenichiro、Pan Jie、Hoshino Akihiro、Suzuki Koji、Yasutomi Motoko、Umetsu Shuichiro、Okada Chizuru、Takagi Masatoshi、Imai Kohsuke、Ohara Osamu、Muise Alexo M.、Okada Satoshi、Morio Tomohiro、Kanegane Hirokazu
  • Journal Title: Journal of Clinical Immunology Volume: - Issue: 4 Pages: 780-790
  • DOI: 10.1007/s10875-021-00975-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Novel Homozygous Mutation Destabilizes IKKβ and Leads to Human Combined Immunodeficiency (2021)
  • Author(s): Qin Tao、Jia Yanjun、Liu Yuhang、Dai Rongxin、Zhou Lina、Okada Satoshi、Tsumura Miyuki、Ohnishi Hidenori、Kato Zenichiro、Kanegane Hirokazu、Sun Xiulian、Zhao Xiaodong
  • Journal Title: Frontiers in Immunology Volume: 11 Pages: 517544-517544
  • DOI: 10.3389/fimmu.2020.517544
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pneumococcal serotype-specific opsonophagocytic activity in interleukin-1 receptor-associated kinase 4-deficient patients. (2021)
  • Author(s): Uehara T, Morino S, Oishi K, Nakamura Y, Togashi N, Imaizumi M, Nishimura S, Okada S, Yara A, Fukushima H, Imagawa K, Takada H.
  • Journal Title: Pediatr Infect Dis J Volume: 40 Issue: 5 Pages: 460-463
  • DOI: 10.1097/inf.0000000000003060
  • Peer Reviewed
• [Journal Article] 先天性免疫異常 (2021)
  • Author(s): 玉浦 萌, 岡田 賢
  • Journal Title: 臨床免疫・アレルギー科 Volume: 75 Pages: 63-76
  • NAID: 40022452477
• [Journal Article] Autosomal recessive complete STAT1 deficiency caused by compound heterozygous intronic mutations (2020)
  • Author(s): Sakata Sonoko、Tsumura Miyuki、Matsubayashi Tadashi、Karakawa Shuhei、Kimura Shunsuke、Tamaura Moe、Okano Tsubasa、Naruto Takuya、Mizoguchi Yoko、Kagawa Reiko、Nishimura Shiho、Imai Kohsuke、Le Voyer Tom、Casanova Jean-Laurent、Bustamante Jacinta、Morio Tomohiro、Ohara Osamu、Kobayashi Masao、Okada Satoshi
  • Journal Title: International Immunology Volume: 32 Issue: 10 Pages: 663-671
  • DOI: 10.1093/intimm/dxaa043
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] IRAK4 Deficiency Presenting with Anti-NMDAR Encephalitis and HHV6 Reactivation (2020)
  • Author(s): Nishimura Shiho、Kobayashi Yoshiyuki、Ohnishi Hidenori、Moriya Kunihiko、Tsumura Miyuki、Sakata Sonoko、Mizoguchi Yoko、Takada Hidetoshi、Kato Zenichiro、Sancho-Shimizu Vanessa、Picard Capucine、Irani Sarosh R.、Ohara Osamu、Casanova Jean-Laurent、Puel Anne、Ishikawa Nobutsune、Okada Satoshi、Kobayashi Masao
  • Journal Title: Journal of Clinical Immunology Volume: 41 Issue: 1 Pages: 125-135
  • DOI: 10.1007/s10875-020-00885-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human STAT1 Gain-of-Function Heterozygous Mutations: Chronic Mucocutaneous Candidiasis and Type I Interferonopathy (2020)
  • Author(s): Okada Satoshi、Asano Takaki、Moriya Kunihiko、Boisson-Dupuis Stephanie、Kobayashi Masao、Casanova Jean-Laurent、Puel Anne
  • Journal Title: Journal of Clinical Immunology Volume: 40 Issue: 8 Pages: 1065-1081
  • DOI: 10.1007/s10875-020-00847-x
  • NAID: 120007168960
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation (2020)
  • Author(s): Matsuda, T. Kambe, N. Hosokawa, J. Ohara, O. Saito, M. K. Nishikomori, R.
  • Journal Title: Annals of the Rheumatic Diseases Volume: 79 Issue: 11 Pages: 1492-1499
  • DOI: 10.1136/annrheumdis-2020-217320
  • Peer Reviewed
• [Journal Article] APRIL-dependent lifelong plasmacyte maintenance and immunoglobulin production in humans (2020)
  • Author(s): Yeh Tzu-Wen、Okano Tsubasa、Naruto Takuya、Yamashita Motoi、Okamura Miko、Tanita Kay、Du Likun、Pan-Hammarstrom Qiang、Mitsuiki Noriko、Okada Satoshi、Kanegane Hirokazu、Imai Kohsuke、Morio Tomohiro
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 146 Issue: 5 Pages: 1109-1120
  • DOI: 10.1016/j.jaci.2020.03.025
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Whole-Exome Sequencing-Based Approach for Germline Mutations in Patients with Inborn Errors of Immunity (2020)
  • Author(s): Okano Tsubasa、Imai Kohsuke、Naruto Takuya、Okada Satoshi、Yamashita Motoi、Yeh Tzu-wen、Ono Shintaro、Tanaka Keisuke、Okamoto Keisuke、Tanita Kay、Matsumoto Kazuaki、Toyofuku Etsushi、Kumaki-Matsumoto Eri、Okamura Miko、Ueno Hiroo、Ogawa Seishi、Ohara Osamu、Takagi Masatoshi、Kanegane Hirokazu、Morio Tomohiro
  • Journal Title: Journal of Clinical Immunology Volume: 40 Issue: 5 Pages: 729-740
  • DOI: 10.1007/s10875-020-00798-3
  • Peer Reviewed
• [Journal Article] Possible involvement of regulatory T cell abnormalities and variational usage of TCR repertoire in children with autoimmune neutropenia (2020)
  • Author(s): Goda S.、Hayakawa S.、Karakawa S.、Okada S.、Kawaguchi H.、Kobayashi M.
  • Journal Title: Clinical & Experimental Immunology Volume: 204 Issue: 1 Pages: 1-13
  • DOI: 10.1111/cei.13559
  • Peer Reviewed
• [Journal Article] Clinical Significance of Serum Soluble TNF Receptor I/II Ratio for the Differential Diagnosis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome From Other Autoinflammatory Diseases (2020)
  • Author(s): Yasumura Junko、Shimizu Masaki、Toma Tomoko、Yashiro Masato、Yachie Akihiro、Okada Satoshi
  • Journal Title: Frontiers in Immunology Volume: 11 Pages: 576152-576152
  • DOI: 10.3389/fimmu.2020.576152
  • Peer Reviewed / Open Access
• [Journal Article] Impaired B-Cell Differentiation in a Patient With STAT1 Gain-of-Function Mutation. (2020)
  • Author(s): Nemoto K, Kawanami T, Hoshina T, Ishimura M, Yamasaki K, Okada S, Kanegane H, Yatera K, Kusuhara K.
  • Journal Title: Front Immunol Volume: 11 Pages: 557521-557521
  • DOI: 10.3389/fimmu.2020.557521
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in a co-culture system with human stimulated X-linked CGD neutrophils (2020)
  • Author(s): Nakamura-Utsunomiya Akari、Tsumura Miyuki、Okada Satoshi、Kawaguchi Hiroshi、Kobayashi Masao
  • Journal Title: PLOS ONE Volume: 15 Issue: 4 Pages: e0230665-e0230665
  • DOI: 10.1371/journal.pone.0230665
  • Peer Reviewed / Open Access
• [Journal Article] Ruxolitinib Response in an Infant With Very-early-onset Inflammatory Bowel Disease and Gain-of-function STAT1 Mutation (2020)
  • Author(s): Acker Karen P.、Borlack Rachel、Iuga Alina、Remotti Helen E.、Soderquist Craig R.、Okada Satoshi、Tsumura Miyuki、Casanova Jean-Laurent、Picoraro Joseph、Puel Anne、Kinberg Sivan、Demirdag Yesim
  • Journal Title: Journal of Pediatric Gastroenterology & Nutrition Volume: 71 Issue: 4
  • DOI: 10.1097/mpg.0000000000002854
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Bone marrow transplantation from a human leukocyte antigen-mismatched unrelated donor in a case with C1q deficiency associated with refractory systemic lupus erythematosus (2020)
  • Author(s): Matsumura Risa、Mochizuki Shinji、Maruyama Natsuki、Morishita Yusuke、Kawaguchi Hiroshi、Okada Satoshi、Tsumura Miyuki、Kaji Shunsaku、Shimizu Junya、Shimada Akira、Kobayashi Masao
  • Journal Title: International Journal of Hematology Volume: 113 Issue: 2 Pages: 302-307
  • DOI: 10.1007/s12185-020-03004-7
  • Peer Reviewed / Open Access
• [Journal Article] Successful allogeneic bone marrow transplantation using immunosuppressive conditioning regimen for a patient with red blood cell transfusion-dependent pyruvate kinase deficiency anemia (2020)
  • Author(s): Shimomura Maiko、Doi Takehiko、Nishimura Shiho、Imanaka Yusuke、Karakawa Shuhei、Okada Satoshi、Kawaguchi Hiroshi、Kobayashi Masao
  • Journal Title: Hematology Reports Volume: 12 Issue: 1 Pages: 8305-8305
  • DOI: 10.4081/hr.2020.8305
  • Peer Reviewed / Open Access
• [Journal Article] ゲノム編集と治療 ゲノム編集技術を活用した重症先天性好中球減少症の治療開発 (2020)
  • Author(s): 今中 雄介, 岡田 賢
  • Journal Title: 医学のあゆみ Volume: 273 Pages: 835-840
• [Journal Article] T+/low B+NK+の表現型を呈した非典型的X連鎖性重症複合免疫不全症 (2020)
  • Author(s): 江口 勇太，土居 岳彦，野間 康輔，浅野 孝基，岡田 賢，小林 正夫
  • Journal Title: 日本小児科学会雑誌 Volume: 123 Pages: 1009-1014
• [Journal Article] リンパ増殖性疾患と原発性免疫不全 (2020)
  • Author(s): 土居 岳彦, 岡田 賢
  • Journal Title: 臨床血液 Volume: 61 Pages: 1365-1372
  • NAID: 130007937083
• [Journal Article] 急性壊死性脳症 (2020)
  • Author(s): 野間康輔, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 366-368
• [Journal Article] Acute liver failure due to NBAS deficiency (2020)
  • Author(s): 藤川 皓基, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 363-365
  • NAID: 40022450096
• [Journal Article] IL-17RC欠損症 (2020)
  • Author(s): 齋藤 聡志, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 354-356
• [Journal Article] DBR1欠損 (2020)
  • Author(s): 坂田 園子, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 351-353
• [Journal Article] IRF3欠損症 (2020)
  • Author(s): 佐倉 文祥, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 348-350
• [Journal Article] RNA polymerase III欠損症 (2020)
  • Author(s): 今中 雄介, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 345-347
• [Journal Article] CD16欠損症 (2020)
  • Author(s): 江藤 昌平, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 339-341
• [Journal Article] IFNAR2欠損症 (2020)
  • Author(s): 郷田 聡, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 335-338
• [Journal Article] IFNAR1欠損症 (2020)
  • Author(s): 郷田 聡, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 331-334
• [Journal Article] IRF9欠損症 (2020)
  • Author(s): 加藤 豊, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 328-330
• [Journal Article] CIB1欠損症 (2020)
  • Author(s): 溝口 洋子, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 325-327
• [Journal Article] JAK1欠損症 (2020)
  • Author(s): 西村 志帆, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 322-324
• [Journal Article] RORγT欠損症 (2020)
  • Author(s): 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 319-321
• [Journal Article] P1104A TYK2 homozygosity (2020)
  • Author(s): 早川 誠一, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 316-318
  • NAID: 40022450587
• [Journal Article] SPPL2a欠損症 (2020)
  • Author(s): 冨岡 啓太, 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 313-315
• [Journal Article] 内因性あるいは自然免疫の異常 概論およびトピックス (2020)
  • Author(s): 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 303-312
• [Journal Article] 研究の進歩 責任遺伝子探索 (2020)
  • Author(s): 岡田 賢
  • Journal Title: 日本臨床 8巻増刊7 原発性免疫不全症候群 Volume: 8 Pages: 21-26
• [Journal Article] Ruxolitinib treatment of a patient with steroid-dependent severe autoimmunity due to STAT1 gain-of-function mutation (2020)
  • Author(s): Moriya K, Suzuki T, Uchida N, Nakano T, Katayama S, Irie M, Rikiishi T, Niizuma H, Okada S, Imai K, Sasahara Y, Kure S
  • Journal Title: Int J Hematol Volume: - Issue: 2 Pages: 258-262
  • DOI: 10.1007/s12185-020-02860-7
  • Peer Reviewed / Open Access
• [Journal Article] A Case Report of a Japanese Boy with Morquio A Syndrome: Effects of Enzyme Replacement Therapy Initiated at the Age of 24 Months (2020)
  • Author(s): Nakamura-Utsunomiya Akari、Nakamae Toshio、Kagawa Reiko、Karakawa Shuhei、Sakata Sonoko、Sakura Fumiaki、Tani Chihiro、Matsubara Yoshiko、Ishino Takashi、Tajima Go、Okada Satoshi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 3 Pages: 989-989
  • DOI: 10.3390/ijms21030989
  • Peer Reviewed / Open Access
• [Journal Article] 非結核性抗酸菌ならびに真菌に易感染性を示す免疫不全症 (2020)
  • Author(s): 岡田 賢
  • Journal Title: 小児科診療 Volume: 83 Pages: 335-340
• [Journal Article] 増刊号 検査項目と異常値からみた-緊急･重要疾患レッドページ 10章 膠原病･免疫疾患 免疫不全症 (2019)
  • Author(s): 浅野 孝基、岡田 賢
  • Journal Title: 臨床検査 Volume: 63 Issue: 4 Pages: 536-537
  • DOI: 10.11477/mf.1542201999
  • ISSN: 0485-1420, 1882-1367
  • Year and Date: 2019-04-15
• [Journal Article] Human gain-of-function STAT1 mutation disturbs IL-17 immunity in mice (2019)
  • Author(s): Tamaura Moe、Satoh-Takayama Naoko、Tsumura Miyuki、Sasaki Takaharu、Goda Satoshi、Kageyama Tomoko、Hayakawa Seiichi、Kimura Shunsuke、Asano Takaki、Nakayama Manabu、Koseki Haruhiko、Ohara Osamu、Okada Satoshi、Ohno Hiroshi、Kobayashi Masao
  • Journal Title: International Immunology Volume: － Issue: 4 Pages: 259-272
  • DOI: 10.1093/intimm/dxz079
  • Peer Reviewed / Open Access
• [Journal Article] Dr. Maeshima, et al, reply (2019)
  • Author(s): MAESHIMA KEISUKE、OKADA SATOSHI、SHIBATA HIROTAKA
  • Journal Title: The Journal of Rheumatology Volume: 46 Issue: 6 Pages: 655-656
  • DOI: 10.3899/jrheum.181455
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Germline-Activating RRAS2 Mutations Cause Noonan Syndrome (2019)
  • Author(s): Niihori Tetsuya、Nagai Koki、Fujita Atsushi、Ohashi Hirofumi、Okamoto Nobuhiko、Okada Satoshi、Harada Atsuko、Kihara Hirotaka、Arbogast Thomas、Funayama Ryo、Shirota Matsuyuki、Nakayama Keiko、Abe Taiki、Inoue Shin-ichi、Tsai I-Chun、Matsumoto Naomichi、Davis Erica E.、Katsanis Nicholas、Aoki Yoko
  • Journal Title: The American Journal of Human Genetics Volume: 104 Issue: 6 Pages: 1233-1240
  • DOI: 10.1016/j.ajhg.2019.04.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gain-of-Function STAT1 Mutation With Familial Lymphadenopathy and Hodgkin Lymphoma (2019)
  • Author(s): Henrickson Sarah E.、Dolan Joseph G.、Forbes Lisa R.、Vargas-Hernandez Alexander、Nishimura Shiho、Okada Satoshi、Kersun Leslie S.、Brodeur Garrett M.、Heimall Jennifer R.
  • Journal Title: Frontiers in Pediatrics Volume: 7 Pages: 160-160
  • DOI: 10.3389/fped.2019.00160
  • Peer Reviewed / Open Access
• [Journal Article] Atypical SIFD with novel TRNT1 mutations: a case study on the pathogenesis of B-cell deficiency (2019)
  • Author(s): Kumaki Eri、Tanaka Keisuke、Imai Kohsuke、Aoki-Nogami Yuki、Ishiguro Akira、Okada Satoshi、Kanegane Hirokazu、Ishikawa Fumihiko、Morio Tomohiro
  • Journal Title: International Journal of Hematology Volume: 109 Issue: 4 Pages: 382-389
  • DOI: 10.1007/s12185-019-02614-0
  • Peer Reviewed
• [Journal Article] メンデル遺伝型マイコバクテリア易感染症（MSMD; Mendelian Susceptibility to Mycobacterial Disease） (2019)
  • Author(s): 浅野 孝基、岡田 賢
  • Journal Title: The Japanese Journal of Pediatric Hematology / Oncology Volume: 56 Issue: 5 Pages: 379-387
  • DOI: 10.11412/jspho.56.379
  • NAID: 130007795815
  • ISSN: 2187-011X, 2189-5384
• [Journal Article] 小児、AYA世代の悪性脳腫瘍サバイバーにおける内分泌学的問題点 GH補充療法を中心に (2019)
  • Author(s): 山崎 文之, 木下 康之, 碓井 智, 岡田 賢, 高野 元気, 米澤 潮, 田口 慧, 宮河 真一郎, 富永 篤, 杉山 一彦, 栗栖 薫
  • Journal Title: 日本内分泌学会雑誌 Volume: 95 Pages: 36-38
• [Journal Article] 発熱、貧血、歩行障害を主訴に小児壊血病を発症した自閉スペクトラム症 (2019)
  • Author(s): 古森 遼太, 土居 岳彦, 野間 康輔, 岡田 賢, 小林 正夫
  • Journal Title: 日本小児科学会雑誌 Volume: 123 Pages: 1283-1289
  • Peer Reviewed
• [Journal Article] 真菌感染症 (2019)
  • Author(s): 玉浦 萌, 岡田 賢
  • Journal Title: 小児内科 Volume: 51 Pages: 1147-1150
• [Journal Article] 成人例も含む国内本態性高Na血症12例での脳弓下器官への特異的抗体解析 (2019)
  • Author(s): 宇都宮 朱里, 檜山 武史, 岡田 賢, 小林 正夫
  • Journal Title: 日本内分泌学会雑誌 Volume: 95 Pages: 34-37
• [Presentation] 原発性免疫不全症とウイルス感染 ～新型コロナウイルスと宿主免疫～ (2022)
  • Author(s): 岡田 賢
  • Organizer: 第5回 日本免疫不全・自己炎症学会総会・学術集会
  • Invited
• [Presentation] 宿主免疫の異常と内分泌障害 (2021)
  • Author(s): 岡田 賢
  • Organizer: 第31回 臨床内分泌代謝Update
  • Invited
• [Presentation] 内分泌障害を合併する原発性免疫不全症 (2021)
  • Author(s): 岡田 賢
  • Organizer: 第54回 日本小児内分泌学会学術集会
  • Invited
• [Presentation] 新型コロナウイルス感染症の重症化と宿主因子 (2021)
  • Author(s): 岡田 賢
  • Organizer: 第53回 日本小児感染症学会総会・学術集会
  • Invited
• [Presentation] 免疫不全症 (2021)
  • Author(s): 岡田 賢
  • Organizer: 日本小児血液がん学会・教育セミナー
  • Invited
• [Presentation] 中枢神経症状を呈する原発性免疫不全症 (2021)
  • Author(s): 岡田 賢
  • Organizer: 第4回 日本免疫不全・自己炎症学会総会・学術集会
  • Invited
• [Presentation] 原発性免疫不全症とウイルス感染症 (2020)
  • Author(s): 岡田 賢
  • Organizer: 第82回 日本血液学会学術集会
• [Presentation] リンパ増殖性疾患と原発性免疫不全 (2020)
  • Author(s): 岡田 賢
  • Organizer: 第82回 日本血液学会学術集会
  • Invited
• [Presentation] 新型コロナウイルス感染と宿主免疫 (2020)
  • Author(s): 岡田 賢
  • Organizer: 第48回日本臨床免疫学会総会
  • Invited
• [Presentation] 免疫疾患の遺伝的背景 (2020)
  • Author(s): 岡田 賢
  • Organizer: 第48回日本臨床免疫学会総会
  • Invited
• [Presentation] 成人期における原発性免疫不全症 (2020)
  • Author(s): 岡田 賢
  • Organizer: 第48回日本臨床免疫学会総会
• [Presentation] 反復する風邪, 重症インフルエンザ感染症・・・：免疫不全症ではないですか？ (2019)
  • Author(s): 岡田 賢
  • Organizer: 日本小児科学会学術集会
  • Invited
• [Presentation] ELANE変異アレル破壊による遺伝子治療の検討 (2019)
  • Author(s): 岡田 賢
  • Organizer: 日本小児科学会学術集会
• [Presentation] 当院で経験した完全型アンドロゲン受容体異常症の5例 (2019)
  • Author(s): 岡田 賢, 坂田園子, 香川礼子, 宇都宮朱里, 兵頭麻希, 神野和彦, 小林正夫
  • Organizer: 日本内分泌学会学術総会
• [Presentation] Primary immunodeficiency caused by gain-of-function mutations in STAT1 (2019)
  • Author(s): Satoshi Okada
  • Organizer: Infectious Diseases Society of Taiwan
  • Invited
• [Remarks] MSMD患者における多発性骨髄炎の発症メカニズムを解明
  • URL: https://www.hiroshima-u.ac.jp/news/65371
• [Remarks] COVID-19による死亡者の約20%、70歳以上の未感染者の約4%がI型IFN中和抗体を保有
  • URL: https://www.hiroshima-u.ac.jp/news/66202
• [Remarks] イントロン領域の複合ヘテロ接合性変異による「常染色体劣性STAT1完全欠損症」を、世界で初めて発見
  • URL: https://www.hiroshima-u.ac.jp/news/58974
• [Remarks] 【研究成果】乳児期に抗NMDAR脳炎を発症したIRAK4欠損症を発見
  • URL: https://www.hiroshima-u.ac.jp/news/60699
• [Remarks] 【研究成果】患者の病態解明に有用なSTAT1-GOF 変異導入マウスを新規に樹立
  • URL: https://www.hiroshima-u.ac.jp/news/56121