Development of predictive diagnostic method for autoimmune diseases on the basis of the mechanism of peripheral self-tolerance induction

• Project/Area Number: 20390168
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Osaka University
• Principal Investigator: IWATANI Yoshinori Osaka University, 大学院・医学系研究科, 教授 (60168581)
• Co-Investigator(Kenkyū-buntansha): WATANABE Mikio 大阪大学, 大学院・医学系研究科, 助教 (50294088)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000); Fiscal Year 2010: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2009: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 発症予知 / 診断法 / 遺伝子多型 / 一塩基多型 / 自己免疫疾患 / 甲状腺 / 重症度 / 末梢性自己寛容 / 制御性T細胞 / 発生制御因子 / GITR / FOXP3 / 甲状線 / Foxel / GITRL / HHEX

Research Abstract

We tried to find the genetic polymorphisms useful for the predictive diagnosis of the development or the prognosis of autoimmune thyroid disease on the basis of the possibilities that the induction factors for peripheral self-tolerance and the regulatory factors for target organ development are related to the pathogenesis of autoimmune thyroid disease (AITD). As a result, we found that SNPs of GITR, Foxp3, HHHEX, Foxel and CTLA-4 were related to the prognosis or the development of AITD, and were useful for the predictive diagnostic methods for AITD.

Research Products

• [Journal Article] Association of functional polymorphisms in promoter regions of IL5, IL6 and IL13 genes with development and prognosis of autoimmune thyroid diseases. (2011)
  • Author(s): Inoue N, Watanabe M, Morita M, Tatusmi K, Hidaka Y, Akamizu T, Iwatani Y.
  • Journal Title: Clin Exp Immunol. 163(3) Pages: 318-323
• [Journal Article] mRNA quantification after fluorescence activated cell sorting using locked nucleic acid probes. (2011)
  • Author(s): Maruo, R., et al
  • Journal Title: Molecular Biotechnology Volume: 49(in press)
  • Peer Reviewed
• [Journal Article] Association of functional polymorphisms in Promoter regions of IL5, IL6 and IL13 genes with development and prognosis of autoimmune thyroid diseases. (2011)
  • Author(s): Inoue, N., et al.
  • Journal Title: Clinical and Experimental Immunology Volume: 163 Pages: 318-323
  • Peer Reviewed
• [Journal Article] Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases. (2010)
  • Author(s): Inoue, N., Watanabe, M., Morita, M., Tomizawa, R., Akamizu, T., Tatsumi, K., Hidaka, Y., Iwatani, Y.
  • Journal Title: Clin Exp Immunol 162(3) Pages: 402-406
• [Journal Article] Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diaeases. (2010)
  • Author(s): Inoue, N., et al.
  • Journal Title: Clinical and Experimental Immunology Volume: 162 Pages: 402-406
  • Peer Reviewed
• [Journal Article] Messenger RNA quantification after fluorescence-activated cell sorting using in situ hybridization. (2010)
  • Author(s): Yamada, H., et al.
  • Journal Title: Cytometry A Volume: 77 Pages: 1032-1037
  • Peer Reviewed
• [Journal Article] Increases in urinary creatinine and blood pressure during early pregnancy in pre-eclampsia (2010)
  • Author(s): Kuromoto, H., et al.
  • Journal Title: Annals of Clinical Biochemistry Volume: 47 Pages: 336-342
  • Peer Reviewed
• [Journal Article] Messenger RNA quantification after fluorescence activated cell sorting using intracellular antigens. (2010)
  • Author(s): Yamada, H., et al.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 397 Pages: 425-428
  • Peer Reviewed
• [Journal Article] Association of -31C/T functional polymorphism in the interleukin-1beta gene with the intractability of Graves' disease and the proportion of Th17 cells. (2009)
  • Author(s): Hayashi, F., Watanabe, M., Nanba, T., Inoue, N., Akamizu, T., Iwatani, Y.
  • Journal Title: Clin Exp Immunol 158(3) Pages: 281-286
• [Journal Article] Increases of the Th1/Th2 cell ratio in severe Hashimoto's disease and in the proportion of Th17 cells in intractable Graves' disease. (2009)
  • Author(s): Nanba, T., Watanabe, M., Inoue, N., Iwatani, Y.
  • Journal Title: Thyroid 19(5) Pages: 495-501
• [Journal Article] Involvement of functional polymorphisms in the TNFA gene in the pathogenesis of autoimmune thyroid diseases and production of anti-TSH receptor antibody. (2009)
  • Author(s): Inoue, N., Watanabe, M., Nanba, T., Wada, M., Akamizu, T., Iwatani, Y.
  • Journal Title: Clin Exp Immunol 156(2) Pages: 199-204
• [Journal Article] Association of -31C/T functional polymorphism in the interleukin-lbeta gene with the intractability of Graves' disease and the proportion of Th17 cells. (2009)
  • Author(s): Hayashi, F., et al.
  • Journal Title: Clinical Experimental Immunology 158 Pages: 281-286
• [Journal Article] Increases of the Th1/Th2 cell ratio in severe Hashimoto's disease and in the proportion of Th17 cells in intractable Graves' disease. (2009)
  • Author(s): Nanba, T., et al.
  • Journal Title: Thyroid 19 Pages: 495-501
• [Journal Article] Involvement of functional polymorphisms in the TNFA gene in the pathogenesis of autoimmune thyroid diseases and production of anti-TSH receptor antibody. (2009)
  • Author(s): Inoue, N., et al.
  • Journal Title: Clinical Experimental Immunology 156 Pages: 199-204
• [Journal Article] Expression of nestin mRNA is a differentiation marker in thyroid tumors. (2009)
  • Author(s): Yamada, H., et al.
  • Journal Title: Cancer Letter 280 Pages: 61-64
• [Journal Article] Acquired activated protein C resistance is associated with IgG antibodies to protein S in patients with systemic lupus erythematosus. (2009)
  • Author(s): Nojima, J., et al.
  • Journal Title: Thrombosis Research 124 Pages: 127-131
• [Journal Article] Clinical utility and characteristics of nine anti-HCV antibody screening reagents used in Japan. (2009)
  • Author(s): Kita, M., et al.
  • Journal Title: Clinical Laboratory 55 Pages: 9-22
• [Journal Article] Early detection of metastasis and relapse of colorectal cancer by recognizing NCA-2 in commercially available CEA assay. (2009)
  • Author(s): Hanada, H., et al.
  • Journal Title: Clinical Chemisty 55 Pages: 1747-1751
• [Journal Article] Postpartum increase of serum thioredoxin concentrations and the relation to CD8 lymphocytes. (2009)
  • Author(s): Kuroda.S., et al.
  • Journal Title: Annals of Clinical Biochemistry 47 Pages: 62-66
• [Journal Article] The 869T/C polymorphism in the transforming growth factor-beta1 gene is associated with the severity and intractability of autoimmune thyroid disease. (2008)
  • Author(s): Yamada H, Watanabe M, Nanba T, Akamizu T, Iwatani Y
  • Journal Title: Clin Exp Immunol 151 Pages: 379-382
• [Journal Article] The-590CC Genotype in the IL4 Gene as a Strong Predictive Factor for the Development of Hypothyroidism in Hashimoto Disease. (2008)
  • Author(s): Nanba T, Watanabe M, Akamizu T, Iwatani Y
  • Journal Title: Clin Chem 54(3) Pages: 621-623
• [Journal Article] Decrease of intrathyroidal CD161+ Valpha24+Vbeta11+ NKT cells in Graves' disease. (2008)
  • Author(s): Watanabe M, Nakamura Y, Matsuzuka F, Takamura Y, Miyauchi A, Iwatani Y
  • Journal Title: Endocrine J 55 Pages: 199-203
• [Journal Article] The 869T/C polymorphism in the transforming growth factor-betal gene is associated with the severity and intractability ofautoimmune thyroid disease. (2008)
  • Author(s): Yamada H, et al
  • Journal Title: Clinical Experimental Immunology 151 Pages: 379-382
  • Peer Reviewed
• [Journal Article] The -590CC genotype in the IL4 gene as a strong predictivefactor for the development of hypothyroidism in Hashimoto Disease. (2008)
  • Author(s): Nanba T, et al
  • Journal Title: Clinical Chemistry 54 Pages: 621-3
  • Peer Reviewed
• [Journal Article] Tissue factor expression on monocytes induced by anti-phospholipid antibodies as a strong risk factor forthromboembolic complications in SLE patients. (2008)
  • Author(s): Noj ima J, et al
  • Journal Title: Biochem Biophys Res Commun 365 Pages: 195-200
  • Peer Reviewed
• [Journal Article] Decrease of intrathyroidal CD161+Valpha24+Vbetall+NKT cellsin Graves' disease. (2008)
  • Author(s): Watanabe M, et al
  • Journal Title: Endocrine Journal 55 Pages: 199-203
  • Peer Reviewed
• [Journal Article] Arteriosclerosis obliterans associated with antti-cardiolipinantibody /{beta}2-glycoprotein I antibodies as a strong riskfactor for ischaemic heart disease in patients with systemiclupus erythematosus. (2008)
  • Author(s): Noi ima J, et al
  • Journal Title: Rheumatology (Oxford) 47 Pages: 684-9
  • Peer Reviewed
• [Journal Article] Association of functional GITR gene polymorphisms related to expression of GITR molecules with prognosis of autoimmune thyroid disease.
  • Author(s): Tomizawa R, Watanabe M, Inoue N, Takemura N, Hidaka Y, Akamizu T, Hayakawa K, Iwatani Y.
  • Journal Title: Clin.Exp.Immunolo. in press
• [Presentation] (Discussed Poster) Association of functional polymorphisms related to the transcriptional level of FOXP3 gene with prognosis of autoimmune thyroid diseases. (2010)
  • Author(s): Watanabe, M., Inoue, N., Morita, M., Tomizawa, R., Akamizu, T., Tatsumi, K., Hidaka, Y., Iwatani, Y.
  • Organizer: 14th International Thyroid Congress (ITC)
  • Place of Presentation: Paris
  • Year and Date: 2010-09-12
• [Presentation] Association of functional polymorphisms related to the transcriptional level of FOXP3 gene with prognosis of autoimmune thyroid diseases. (2010)
  • Author(s): Watanabe, M., et al.
  • Organizer: 14th International Thyroid Congress
  • Place of Presentation: Paris, France
  • Year and Date: 2010-09-12
• [Presentation] Increases of the Th1/Th2 cell ratio in severe Hashimoto's disease and in the proportion of Th17 cells in intractable Graves' disease. (2010)
  • Author(s): Watanabe, M., Nanba, T., Inoue, N., Iwatani, Y.
  • Organizer: 14th International Congress of Endocrinology (ICE)
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-30
• [Presentation] Involvement of the functional polymorphisms in TNFA gene in the pathogenesis of autoimmune thyroid diseases and the production of anti-TSH receptor antibody. (2009)
  • Author(s): Inoue, N., Watanabe, M., Nanba, T., Akamizu, T., Iwatani, Y.
  • Organizer: 9th Congress of the Asia and Oceania Thyroid Association (AOTA)
  • Place of Presentation: Nagoya
  • Year and Date: 2009-11-02
• [Presentation] Association of the -31C/T functional polymorphism in the interleukin-1β gene with the intractability of Graves' disease and the proportion of Th17 cells. (2009)
  • Author(s): Watanabe, M., Hayashi, F., Nanba, T., Inoue, N., Akamizu, T., Iwatani, Y.
  • Organizer: 80th Annual Meeting of the American Thyroid Association
  • Place of Presentation: Palm Beach
  • Year and Date: 2009-09-26
• [Presentation] Association of the -31C/T functional polymorphism in the interleukin-lbeta gene with the intractability of Graves' disease and the proportion of Th17 cells. (2009)
  • Author(s): Watanabe, M., et al.
  • Organizer: The 80^<th> Annual Meeting of the American Thyroid Association
  • Place of Presentation: Palm Beach, FL, USA
  • Year and Date: 2009-09-26
• [Presentation] Patients of Hashimoto's disease with-590CC genotype in the IL4 gene would develop hypothyroidism. (2008)
  • Author(s): Watanabe M, Namba T, Akamizu T, Iwatani Y
  • Organizer: The 79th Annual Meeting of the American Thyroid Association
  • Place of Presentation: Chicago, IL
  • Year and Date: 2008-10-03
• [Presentation] Patients of Hashimoto' s disease with -590CC genotype in the IL4 gene would develop hypothyroidism. (2008)
  • Author(s): Watanabe M, et al
  • Organizer: The 79^<th> Annual Meeting of the American Thyroid Association
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2008-10-03
• [Book] 臨床検査学実習書シリーズ遺伝子検査学実習書 (2010)
  • Author(s): 岩谷良則編
  • Publisher: 医歯薬出版株式会社