Prevention of the onset of Graves' disease using high sensitivity method for TSH receptor antibody

• Project/Area Number: 23590671
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Osaka University
• Principal Investigator: HIDAKA YOH 大阪大学, 医学(系)研究科(研究院), 准教授 (30243231)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: バセドウ病 / TSHレセプター抗体

Research Abstract

We examined the correlation between the levels of TSH receptor antibody (TRAb) and cytokines in the supernatant incubated with the peripheral blood mononuclear cells (PBMCs) from the patients with Graves' disease in order to analyze the mechanism of onset of Graves' disease. However we could not find the correlation between the level of TRAb and cytokines.
We tried to find the drugs that could suppress the production of TRAb in order to prevent the onset of Graves' disease. However the production of TRAb was not suppressed by anti-thyroid drug (methimazol) and anti-CD20 monoclonal antibody (rituximab).

Research Products

• [Journal Article] An improved protocol for mRNA quantification after fluorescence activated cell sorting with an increased signal to noise ratio in flow cytometry (2014)
  • Author(s): Date, A., Maeda, T., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T
  • Journal Title: Mol Biotechnol Volume: (in press) Issue: 7 Pages: 591-598
  • DOI: 10.1007/s12033-014-9733-5
  • Peer Reviewed
• [Journal Article] The GG genotype of the 1125G/T polymorphism in the EPO gene protects against the development of Graves' disease (2013)
  • Author(s): Inoue, N. Watanabe, M., Nobuhara, T., Hidaka, Y., Iwatani, Y
  • Journal Title: Immunol Letters Volume: 156 Issue: 1-2 Pages: 156-158
  • DOI: 10.1016/j.imlet.2013.10.006
  • Peer Reviewed
• [Journal Article] Different genotypes of a functional polymorphism of the TSHR gene are associated with the development and severity of Graves and Hashimotos diseases (2013)
  • Author(s): Inoue, N., Watanabe, M., Katsumata, Y., Hidaka, Y., Iwatani, Y
  • Journal Title: Tissue Antigen Volume: 82 Issue: 4 Pages: 288-290
  • DOI: 10.1111/tan.12190
  • Peer Reviewed
• [Journal Article] IL-10 -592A/C polymorphism is associated with severity of Hashimoto's disease (2013)
  • Author(s): Inoue, N., Watanabe, M., Wada, M., Morita, M., Hidaka, Y., Iwatani, Y
  • Journal Title: Cytokine Volume: 64 Issue: 1 Pages: 370-374
  • DOI: 10.1016/j.cyto.2013.05.014
  • Peer Reviewed
• [Journal Article] Pseudohypoglycemia or hyperglycemia caused by interference with self-monitoring blood glucose measurements in anticancer ascorbic acid therapy (2013)
  • Author(s): Kimura T, Kozawa J, Matsui M, Nishizawa H, Yasuda T, Otsuki M, Iwahashi H, Kaneto H, Funahashi T, Hidaka Y, Imagawa A, Shimomura I
  • Journal Title: Journal of Diabetes Investigation Volume: 4(6) Issue: 6 Pages: 679-680
  • DOI: 10.1111/jdi.12108
  • Peer Reviewed
• [Journal Article] Preparation of thyroid follicular cells for mRNA quantifi cation after fl uorescence-activated cell sorting (2013)
  • Author(s): Matsumoto, C., Ito, M., Yamada, H., Yoshida, H., Watanabe, M., Hidaka, Y., Iwatani, Y., Miyauchi, A., Takano, T
  • Journal Title: Scandinavian Journal of Clinical & Laboratory Investigation Volume: 73 Issue: 3 Pages: 245-252
  • DOI: 10.3109/00365513.2013.769624
  • Peer Reviewed
• [Journal Article] The association between a functional polymorphism in the CD24 gene and the development of autoimmune thyroid diseases (2013)
  • Author(s): Inoue, N., Watanabe, M., Hayashi F., Hidaka, Y., Iwatani, Y
  • Journal Title: Tissue Antigen Volume: 81(3) Issue: 3 Pages: 161-3
  • DOI: 10.1111/tan.12070
  • Peer Reviewed
• [Journal Article] Genes that characterize T3-predominant Graves' thyroid tissues (2013)
  • Author(s): Matsumoto, C., Ito, M., Yamada, H., Yamakawa, N., Yoshida, H., Date, A., Watanabe, M., Hidaka, Y., Iwatani, Y., Miyauchi, A., Takano, T
  • Journal Title: Eur J Endocrinol Volume: 168(2) Issue: 2 Pages: 137-44
  • DOI: 10.1530/eje-12-0507
  • Peer Reviewed
• [Journal Article] Genes that characterize T3-predominant Graves' thyroid tissues. (2013)
  • Author(s): Matsumoto C, Ito M, Yamada H, Yamakawa N, Yoshida H, Date A, Watanabe M, Hidaka Y, Iwatani Y, Miyauchi A, Takano T
  • Journal Title: Eur J Endocrinol Volume: 168(2) Pages: 137-144
  • Peer Reviewed
• [Journal Article] The association between a functional polymorphism in the CD24 gene and the development of autoimmune thyroid diseases. (2013)
  • Author(s): Inoue N, Watanabe M, Hayashi F, Hidaka Y, Iwatani Y
  • Journal Title: Tissue Antigen Volume: 81(3) Pages: 161-163
  • Peer Reviewed
• [Journal Article] Associations between autoimmune thyroid disease prognosis and functional polymorphisms of susceptibility genes, CTLA4, PTPN22, CD40, FCRL3, and ZFAT, previously revealed in Genome-wide association studies (2012)
  • Author(s): Inoue, N. Watanabe, M., Yamada, H., Takemura, K., Hayashi, F., Yamakawa, N., Akahane, M., Shimizuishi, Y., Hidaka, Y., Iwatani, Y
  • Journal Title: J Clin Immunol Volume: 32 Issue: 6 Pages: 1243-52
  • DOI: 10.1007/s10875-012-9721-0
  • Peer Reviewed
• [Journal Article] Thyroid Function Influences Serum Apolipoprotein B-48 Levels in Patients with Thyroid Disease (2012)
  • Author(s): Mugii S, Hanada H, Okubo M, Masuda D, Takeoka K, Hidaka Y, Ohama T, Matsuyama A, Nakagawa-Toyama Y, Nishida M, Ishigami M, Komuro I, Yamashita S
  • Journal Title: J Atheroscler Thromb Volume: 19(10) Pages: 890-896
  • URL: https://www.jstage.jst.go.jp/article/jat/19/10/19_12757/_pdf
  • Peer Reviewed
• [Journal Article] Association ofpolymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR, and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease (2012)
  • Author(s): Arakawa, Y., Watanabe, M., Inoue, N., Sarumaru, M., Hidaka, Y., Iwatani, Y
  • Journal Title: Clin Exp Immunol Volume: 170(2) Issue: 2 Pages: 194-201
  • DOI: 10.1111/j.1365-2249.2012.04646.x
  • Peer Reviewed
• [Journal Article] Measurement of TFF3 mRNA in aspirates from thyroid nodules using mesh filtration : The first clinical trial in 130 cases (2012)
  • Author(s): Yamada H, Takano T, Kihara M, Hirokawa M, Yoshida H, Watanabe M, Iwatani Y, Hidaka Y, Miyauchi A
  • Journal Title: Endocr J Volume: 59(7) Pages: 621-630
  • URL: https://www.jstage.jst.go.jp/article/endocrj/59/7/59_EJ12-0077/_pdf
  • Peer Reviewed
• [Journal Article] Prolonged hybridization with a cRNA probe improves the signal to noise ratio for in-tube in situ hybridization for quantification of mRNA after fluorescence-activated cell sorting (2012)
  • Author(s): Yamada, H., Yamakawa, N., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T.
  • Journal Title: Biotech Histochem Volume: (in press) Issue: 5 Pages: 366-71
  • DOI: 10.3109/10520295.2012.672650
  • Peer Reviewed
• [Journal Article] Preparation of a cut-off solution that gives a clear index for distinguishing Le(a-b-) sera in CA19-9 assays using SphereLight 180 and Architect i2000 kits. (2012)
  • Author(s): Hanada, H. et al.
  • Journal Title: Clinica Chemica Acta Volume: 413 Issue: 1-2 Pages: 278-281
  • DOI: 10.1016/j.cca.2011.09.009
  • Peer Reviewed
• [Journal Article] Prolonged hybridization with a cRNA probe improves the signal to noise ratio for in-tube in situ hybridization for quantification of mRNA after fluorescence-activated cell sorting. (2012)
  • Author(s): Yamada H, Yamakawa N, Watanabe M, Hidaka Y, Iwatani Y, Takano T
  • Journal Title: Biotech Histochem Volume: 87(5) Pages: 366-371
  • Peer Reviewed
• [Journal Article] Measurement of TFF3 mRNA in aspirates from thyroid nodules using mesh filtration: The first clinical trial in 130 cases. (2012)
  • Author(s): Yamada H, Takano T, Kihara M, Hirokawa M, Yoshida H, Watanabe M, Iwatani Y, Hidaka Y, Miyauchi A
  • Journal Title: Endocr J Volume: 59(7) Pages: 621-630
  • Peer Reviewed
• [Journal Article] Association of polymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR, and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease. (2012)
  • Author(s): ArakawaY, Watanabe M, Inoue N, Sarumaru M, Hidaka Y, Iwatani Y
  • Journal Title: Clin Exp Immunol Volume: 170(2) Pages: 194-201
  • Peer Reviewed
• [Journal Article] Thyroid Function Influences Serum Apolipoprotein B-48 Levels in Patients with Thyroid Disease. (2012)
  • Author(s): Mugii S, Hanada H, Okubo M, Masuda D, Takeoka K, Hidaka Y, Ohama T, Matsuyama A, Nakagawa-Toyama Y, Nishida M, Ishigami M, Komuro I, Yamashita S
  • Journal Title: J Atheroscler Thromb Volume: 19(10) Pages: 890-896
  • Peer Reviewed
• [Journal Article] Associations between autoimmune thyroid disease prognosis and functional polymorphisms of susceptibility genes, CTLA4, PTPN22, CD40, FCRL3, and ZFAT, previously revealed in Genome-wide association studies. (2012)
  • Author(s): Inoue N, Watanabe M, Yamada H, Takemura K, Hayashi F, Yamakawa N, Akahane M, Shimizuishi Y, Hidaka Y, Iwatani Y
  • Journal Title: J Clin Immunol Volume: 32(6) Pages: 1243-1252
  • Peer Reviewed
• [Journal Article] Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 (2012)
  • Author(s): Hanada H, Mugii S, Okubo M, Maeda I, Kuwayama K, Hidaka Y, et.al.
  • Journal Title: Clin Chim Acta Volume: 413 Pages: 160-165
  • Peer Reviewed
• [Journal Article] A solution for distinguishing Le(a-b-) sera in CA19-9 assays using SphereLight 180 and Architect i2000 assays. (2012)
  • Author(s): Hanada H, Mugii S, Takeoka K, Maeda I, Watanabe M, Hidaka Y, Iwatani Y
  • Journal Title: Clin Chim Acta Volume: 413 Pages: 278-281
  • Peer Reviewed
• [Journal Article] Functional polymorphisms in TBX21 and HLX are associated with development and (2012)
  • Author(s): Morita M, Watanabe M, Inoue N, Inaoka C, Akamizu T, Tatsumi K, Hidaka Y, Iwatani Y
  • Journal Title: Autoimmunity Volume: 45 Pages: 129-136
  • Peer Reviewed
• [Journal Article] Functional polymorphisms in TBX21 and HLX are associated with development and prognosis of Graves' disease (2011)
  • Author(s): Morita, M., Watanabe, M., Inoue, N., Inaoka, C., Akamizu, T., Tatsumi, K., Hidaka, Y., Iwatani, Y.
  • Journal Title: Autoimmunity Volume: 45(2) Issue: 2 Pages: 129-36
  • DOI: 10.3109/08916934.2011.622013
  • Peer Reviewed
• [Presentation] 胎児性甲状腺細胞検出のための高感度FACS-mQの開発 (2013)
  • Author(s): 伊達亜理沙, 高野徹, 渡邉幹夫, 日高洋, 岩谷良則
  • Organizer: 日本甲状腺学会第56回
  • Place of Presentation: 和歌山
  • Year and Date: 2013-11-15
• [Presentation] 検査目的に適合した検体の質を確保するための検体保存評価法の検討―標準化委員会プロジェクト報告― (2013)
  • Author(s): 池田勝義, 大久保滋夫, 松下一之, 松本祐之, 日高洋, 康東天, 橋口照人, 土屋達行, 吉田耕, 前川真人
  • Organizer: 日本臨床検査意学会総会第60回
  • Place of Presentation: 神戸
  • Year and Date: 2013-11-03
• [Presentation] PD-1遺伝子の機能的多型及びPD-1発現強度と自己免疫性甲状腺疾患の病因・病態との関係 (2013)
  • Author(s): 川端麻友美, 渡邉幹夫, 小林彩香, 井上直哉, 日高洋, 岩谷良則
  • Organizer: 日本臨床化学会年会第53回
  • Place of Presentation: 徳島
  • Year and Date: 2013-08-31
• [Presentation] 凝固因子インヒビター測定法における血漿pHの安定化法 (2013)
  • Author(s): 竹尾映美, 末久悦次, 川崎富夫, 徳雅幸, 林貞夫, 日高洋
  • Organizer: 日本検査血液学会第14回
  • Place of Presentation: 東京
  • Year and Date: 2013-07-27
• [Presentation] 全ゲノム関連解析による自己免疫性甲状腺疾患関連遺伝子:CTLA4、PTPN22、CD40、FCRL3、ZFATの機能的多型と病態予後との関係 (2012)
  • Author(s): 渡邉幹夫, 井上直哉, 山田宏哉, 武村和哉, 林文明, 山川法子, 赤羽舞子, 清水石裕, 日高洋, 岩谷良則
  • Organizer: 日本甲状腺学会第55回
  • Place of Presentation: 福岡
  • Year and Date: 2012-11-30
• [Presentation] 自己免疫甲状腺疾患における病態とskewed X-chromosome inactivationとの関連 (2012)
  • Author(s): 石戸奈穂子, 井上直哉, 渡邉幹夫, 日高洋, 岩谷良則
  • Organizer: 日本臨床検査意学会総会第59回
  • Place of Presentation: 京都
  • Year and Date: 2012-11-30
• [Presentation] CTLA4, PTPN22, CD40,FCRL3, ZFAT遺伝子の個体差と自己免疫性甲状腺疾患の病態予後との関連 (2012)
  • Author(s): 井上直哉, 渡邉幹夫, 武村和哉, 林貞夫, 日高洋, 岩谷良則
  • Organizer: 日本臨床化学会年会第52回
  • Place of Presentation: 盛岡
  • Year and Date: 2012-09-08
• [Presentation] 妊娠初期に投与されたチアマゾールの妊娠結果に与える影響に関する前向き研究(POEMスタディ):中間報告 (2011)
  • Author(s): 荒田尚子, 村島温子, 伊藤真也, 大橋靖雄, 小野瀬裕之, 窪田純久, 田尻淳一, 浜田昇, 日高洋, 深田修司, 百渓尚子, 小崎健次郎, 小崎里華, 吉川裕之
  • Organizer: 日本甲状腺学会第54回
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-23
• [Presentation] 新規臨床検査法、FACS-mQの開発 (2011)
  • Author(s): 高野徹, 日高洋, 岩谷良則
  • Organizer: 日本臨床検査意学会総会第58回
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-18
• [Presentation] Dnmt1, 3a, 3bの遺伝子多型と自己免疫性甲状腺疾患の病態との関連 (2011)
  • Author(s): 荒川裕也, 渡邉幹夫, 井上直哉, 日高洋, 巽圭太, 岩谷良則
  • Organizer: 日本臨床化学会年会第51回
  • Place of Presentation: 札幌
  • Year and Date: 2011-08-27
• [Book] 甲状腺, 副甲状腺, 標準臨床検査医学 (2013)
  • Author(s): 日高洋
  • Publisher: 医学書院
• [Book] 標準臨床検査医学（甲状腺、副甲状腺の章を分担執筆） (2013)
  • Author(s): 日高 洋
  • Publisher: 医学書院
• [Book] 甲状腺機能亢進症・低下症, 臨床検査のガイドライン (2012)
  • Author(s): 日高洋
  • Publisher: 宇宙堂八木書店
• [Book] 原発性甲状腺機能低下症の診療のポイント, 代謝・内分泌疾患診療最新ガイドライン (2012)
  • Author(s): 日高洋
  • Publisher: 総合医学社
• [Book] 臨床検査のガイドライン（甲状腺機能亢進症・低下症の章を分担執筆） (2012)
  • Author(s): 日高 洋
  • Publisher: 宇宙堂八木書店
• [Book] バセドウ病治療ガイドライン2011 (2011)
  • Author(s): 阿部好文, 網野信行, 飯高誠, 伊藤公一, 岡村建, 小澤安則, 上條桂一, 窪田純久, 佐々木純, 紫芝良昌, 田尻淳一, 田中祐司, 對馬敏夫, 中村浩淑, 浜田昇, 日高洋, 深田修司, 三橋知明, 宮内昭, 百渓尚子, 吉村弘, 内村英正, 岡本泰之, 小西淳二, 中駄邦博, 野口靖志, 御前隆
  • Publisher: 南江堂
• [Book] 無痛性甲状腺炎・亜急性甲状腺炎, 外来でどう診る?甲状腺疾患 (2011)
  • Author(s): 日高洋
  • Publisher: 日本医事新報社