Development of an animal model of Stevens-Johnson syndrome induced by drugs.

• Project/Area Number: 16K15154
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: University of Tsukuba
• Principal Investigator: FURUKAWA HIROSHI 筑波大学, 医学医療系, 准教授 (00372293)
• Co-Investigator(Renkei-kenkyūsha): TSUCHIYA NAOYUKI 筑波大学, 医学医療系, 教授 (60231437)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヒトの薬物動態・代謝予測系 / 皮膚薬剤過敏症

Outline of Final Research Achievements

Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening drug adverse effects and are associated with human leukocyte antigen (HLA). Established animal models of Stevens-Johnson syndrome are using graft versus host effects. Thus, it was tried to develop an animal model of Stevens-Johnson syndrome induced by carbamazepine. Stevens-Johnson syndrome was not induced with carbamazepine in the transgenic mouse of HLA-A*31:01, a susceptibility allele for carbamazepine-induced Stevens-Johnson syndrome. The treatment with Poly (I:C) or irradiation did not enhance the development of Stevens-Johnson syndrome in the transgenic mouse of HLA-A*31:01.

Research Products

• [Journal Article] Association of a single nucleotide polymorphism in TNIP1 with type-1 autoimmune hepatitis in the Japanese population. (2018)
  • Author(s): Oka S, Higuchi T, Furukawa H, Nakamura M, Komori A, Abiru S, Nagaoka S, Hashimoto S, Naganuma A, Naeshiro N, Yoshizawa K, Shimada M, Nishimura H, Tomizawa M, Kikuchi M, Makita F, Yamashita H, Ario K, Yatsuhashi H, Tohma S, Kawasaki A, Tsuchiya N, Migita K.
  • Journal Title: J Hum Genet. Volume: 印刷中 Issue: 6 Pages: 739-744
  • DOI: 10.1038/s10038-018-0440-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of ETS1 polymorphism with granulomatosis with polyangiitis and proteinase 3-anti-neutrophil cytoplasmic antibody positive vasculitis in a Japanese population (2018)
  • Author(s): A Kawasaki, K Yamashita, F Hirano, KE Sada, D Tsukui, Y Kondo, Y Kimura, K Asako, S Kobayashi, H Yamada, H Furukawa, K Nagasaka, T Sugihara, K Yamagata, T Sumida, S Tohma, H Kono, S Ozaki, S Matsuo, H Hashimoto, H Makino, Y Arimura, M Harigai, N Tsuchiya
  • Journal Title: Journal of Human Genetics Volume: 63 Issue: 1 Pages: 55-62
  • DOI: 10.1038/s10038-017-0362-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biomarker for nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis: anti-glycopeptidolipid core antigen immunoglobulin A antibodies. (2018)
  • Author(s): Iwata K, Oka S, Tsuno H, Furukawa H, Shimada K, Hashimoto A, Komiya A, Tsuchiya N, Katayama M, Tohma S.
  • Journal Title: Mod Rheumatol. Volume: 28 Issue: 2 Pages: 271-275
  • DOI: 10.1080/14397595.2017.1336866
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype (2017)
  • Author(s): Oka Shomi、Furukawa Hiroshi、Yasunami Michio、他
  • Journal Title: PLOS ONE Volume: 12 Issue: 10 Pages: e0187325-e0187325
  • DOI: 10.1371/journal.pone.0187325
  • NAID: 120007128808
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Incidence and risk factors for infections requiring hospitalization, including pneumocystis pneumonia, in Japanese patients with rheumatoid arthritis. (2017)
  • Author(s): Hashimoto A, Suto S, Horie K, Fukuda H, Nogi S, Iwata K, Tsuno H, Ogihara H, Kawakami M, Komiya A, Furukawa H, Matsui M, Tohma S.
  • Journal Title: Int J Rheumatol. Volume: 2017 Pages: 6730812-6730812
  • DOI: 10.1155/2017/6730812
  • NAID: 120007134663
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still's disease. (2017)
  • Author(s): Asano T, Furukawa H, Sato S, Yashiro M, Kobayashi H, Watanabe H, Suzuki E, Ito T, Ubara Y, Kobayashi D, Iwanaga N, Izumi Y, Fujikawa K, Yamasaki S, Nakamura T, Koga T, Shimizu T, Umeda M, Nonaka F, Yasunami M, Ueki Y, Eguchi K, Tsuchiya N, Tohma S, Yoshiura KI, Ohira H, Kawakami A, Migita K.
  • Journal Title: Arthritis Res Ther. Volume: 19 Issue: 1 Pages: 199-199
  • DOI: 10.1186/s13075-017-1406-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Response to: ‘HLA-A 31:01 is not associated with the development of methotrexate pneumonitis in the UK population: results from a genome wide association study.’ by Bluett et al. (2017)
  • Author(s): Furukawa H, Oka S, Shimada K, Tsuchiya N, Tohma S, the Rheumatoid Arthritis associated Interstitial Lung Disease Study Consortium.
  • Journal Title: Ann Rheum Dis. Volume: 76 Issue: 12 Pages: e52-e53
  • DOI: 10.1136/annrheumdis-2017-211518
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis. (2017)
  • Author(s): Terao C, Kawaguchi T, Dieude P, Varga J, Kuwana M, Hudson M, Kawaguchi Y, Matucci-Cerinic M, Ohmura K, Riemekasten G, Kawasaki A, Airo P, Horita T, Oka A, Hachulla E, Yoshifuji H, Caramaschi P, Hunzelmann N, Baron M, Atsumi T, Hassoun P, Torii T, Takahashi M, et al.
  • Journal Title: Ann Rheum Dis. Volume: 印刷中 Issue: 6 Pages: 1150-1158
  • DOI: 10.1136/annrheumdis-2016-210645
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial. (2017)
  • Author(s): Izumi Y, Akazawa M, Akeda Y, Tohma S, Hirano F, Ideguchi H, Matsumura R, Miyamura T, Mori S, Fukui T, Iwanaga N, Jiuchi Y, Kozuru H, Tsutani H, Saisyo K, Sugiyama T, Suenaga Y, Okada Y, Katayama M, Ichikawa K, Furukawa H, Kawakami K, Oishi K, Migita K.
  • Journal Title: Arthritis Res Ther. Volume: 19 Issue: 1 Pages: 15-15
  • DOI: 10.1186/s13075-016-1207-7
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Common Protective Alleles HLA-DRB1*13 Among Systemic Autoimmune Diseases. (2017)
  • Author(s): Furukawa H, Oka S, Tsuchiya N, Shimada K, Hashimoto A, Tohma S, Kawasaki A.
  • Journal Title: Genes Immun. Volume: 18 Issue: 1 Pages: 1-7
  • DOI: 10.1038/gene.2016.40
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasma miRNA Expression Profiles in Rheumatoid Arthritis Associated Interstitial Lung Disease. (2017)
  • Author(s): Oka S, Furukawa H, Shimada K, Hashimoto A, Komiya A, Fukui N, Tsuchiya N, Tohma S.
  • Journal Title: BMC Musculoskelet Disord. Volume: 18 Issue: 1 Pages: 21-21
  • DOI: 10.1186/s12891-017-1389-4
  • NAID: 120007134825
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association of a single nucleotide polymorphism upstream of ICOS with Japanese autoimmune hepatitis type 1. (2017)
  • Author(s): Higuchi T, Oka S, Furukawa H, Nakamura M, Komori A, Abiru S, Nagaoka S, Hashimoto S, Naganuma A, Naeshiro N, Yoshizawa K, Shimada M, Nishimura H, Tomizawa M, Kikuchi M, Makita F, Yamashita H, Ario K, Yatsuhashi H, Tohma S, Kawasaki A, Ohira H, Tsuchiya N, Migita K.
  • Journal Title: J Hum Genet. Volume: in press Issue: 4 Pages: 481-484
  • DOI: 10.1038/jhg.2016.155
  • NAID: 40021158271
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Independent Association of HLA-G 3’ Untranslated Region 14bp Indel Polymorphism with Systemic Lupus Erythematosus in a Japanese Population: a Case-control Association Study. (2016)
  • Author(s): Hachiya Y, Kawasaki A, Oka S, Kondo Y, Ito S, Matsumoto I, Kusaoi M, Amano H, Suda A, Setoguchi K, Nagai T,Shimada K, Sugii S, Okamoto A, Chiba N, Suematsu E, Ohno S, Katayama M, Kono H, Hirohata S, Takasaki Y, Hashimoto H, Sumida T, Nagaoka S, Tohma S, Furukawa H, Tsuchiya N.
  • Journal Title: PLoS ONE. Volume: 11 Issue: 6 Pages: 22-22
  • DOI: 10.1371/journal.pone.0158065
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protective role of HLA-DRB1*13:02 against microscopic polyangiitis and MPO-ANCA positive vasculitis in a Japanese population: a case-control study. (2016)
  • Author(s): Kawasaki A, Hasebe N, Hidaka M, Hirano F, Sada K, Kobayashi S, Yamada H, Furukawa H, Yamagata K, Sumida T, Miyasaka N, Tohma S, Ozaki S, Matsuo S, Hashimoto H, Makino H, Arimura Y, Harigai M, Tsuchiya N.
  • Journal Title: PLoS ONE. Volume: 11 Issue: 5 Pages: e0154393-e0154393
  • DOI: 10.1371/journal.pone.0154393
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human Leukocyte Antigen and Systemic Sclerosis in Japanese: The Sign of the Four Independent Protective Alleles, DRB1*13:02, DRB1*14:06, DQB1*03:01, and DPB1*02:01. (2016)
  • Author(s): Furukawa H, Tohma S, Tsuchiya N, et al
  • Journal Title: PLoS One. Volume: 11(4) Issue: 4 Pages: e0154255-e0154255
  • DOI: 10.1371/journal.pone.0154255
  • NAID: 120007135446
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] HLAクラスIIと強皮症 (2017)
  • Author(s): 古川宏,岡笑美,川崎綾,島田浩太,杉井章二,松下貴史,橋本篤,小宮明子,福井尚志,小林幸司,長田侑,井畑淳,近藤裕也,永井立夫,瀬戸口京吾,岡本明子,岡本享,千葉実行,末松栄一,河野肇,片山雅夫,廣畑俊成,住田孝之,右田清志,長谷川稔,藤本学,佐藤伸一,長岡章平,竹原和彦,當間重人,土屋尚之
  • Organizer: 第20回強皮症研究会議
  • Place of Presentation: アステラス製薬本社(東京都中央区)
  • Year and Date: 2017-01-14
• [Presentation] 自己免疫性肝炎とTNIP1遺伝子多型の関連 (2017)
  • Author(s): 岡笑美,古川宏,當間重人,川崎綾,土屋尚之, 右田清志
  • Organizer: 第28回日本リウマチ学会関東支部学術集会
• [Presentation] 食餌によるメトトレキサート毒性の増強 (2017)
  • Author(s): 樋口貴士,吉村美郁,岡笑美,川崎綾,蕨栄治,水野聖哉,小野栄夫,高橋智,當間重人,土屋尚之,古川宏
  • Organizer: 第38回日本臨床薬理学会学術総会
• [Presentation] 食餌によるメトトレキサート毒性の増強 (2017)
  • Author(s): 樋口貴士,吉村美郁,岡笑美,川崎綾,蕨栄治,水野聖哉,小野栄夫,高橋智,當間重人,土屋尚之,古川宏
  • Organizer: 第28回日本リウマチ学会関東支部学術集会
• [Presentation] 関節リウマチとの比較による変形性関節症の滑膜病変の成立機序に関する検討 (2017)
  • Author(s): 福井尚志,田中信帆,田代俊之,桂川陽三,古川宏,大橋暁,増田公男,岩澤三康,森俊仁,當間重人
  • Organizer: 第28回日本リウマチ学会関東支部学術集会
• [Presentation] 自己免疫性肝炎とTNIP1遺伝子多型の関連 (2017)
  • Author(s): 岡笑美,古川宏,當間重人,川崎綾,土屋尚之, 右田清志
  • Organizer: 第61回日本リウマチ学会
• [Presentation] 自己免疫性肝炎とTNIP1遺伝子多型の関連 (2017)
  • Author(s): 岡笑美,古川宏,當間重人,川崎綾,土屋尚之,右田清志
  • Organizer: 第71回国立病院総合医学会
• [Presentation] 変形性関節症と関節リウマチの滑膜組織におけるmiRNA の発現比較 (2017)
  • Author(s): 田中信帆,田代俊之,桂川陽三,古川宏,大橋暁,増田公男,岩澤三康,森俊仁,當間重人,福井尚志
  • Organizer: 第28回日本リウマチ学会関東支部学術集会
• [Presentation] 関節リウマチ関連間質性肺病変における血漿中miRNA (2016)
  • Author(s): 岡笑美,古川宏,島田浩太,橋本篤,小宮明子,土屋尚之,當間重人
  • Organizer: 第70回国立病院総合医学会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県宜野湾市)
  • Year and Date: 2016-11-11
• [Presentation] 日本人全身性エリテマトーデスとHLA-G多型の関連 (2016)
  • Author(s): 川崎綾,八谷有紀,古川宏,近藤裕也,伊藤聡,松本功,草生真規雄,天野浩文,須田昭子,長岡章平,瀬戸口京吾,永井立夫,廣畑俊成,島田浩太,杉井章二,岡本享,千葉実行,末松栄一,大野滋,片山雅夫,河野肇,髙崎芳成,橋本博史,住田孝之,當間重人,土屋尚之
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-04-21
• [Presentation] 関節リウマチに合併する間質性肺病変と血漿中miRNA発現 (2016)
  • Author(s): 岡笑美,古川宏,島田浩太,橋本篤,小宮明子,土屋尚之,當間重人
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-04-21
• [Book] 「強皮症の基礎と臨床：病態の解明から最新の診療まで」（佐藤伸一編） (2016)
  • Author(s): 八谷有紀,古川宏,土屋尚之:遺伝因子 共著 分担執筆
  • Total Pages: 10
  • Publisher: 医薬ジャーナル社