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Isolation, analysis and constitution of Immunoglobulin encoding autoantibodies

Research Project

Project/Area Number 05671922
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Laboratory medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

AKAMIZU Takashi  Kyoto Univ., Dept.of Labo.Med.Assist.Prof., 医学部, 助手 (20231813)

Co-Investigator(Kenkyū-buntansha) MATSUDA Fumihiko  Kyoto Univ., Cent.for Mol.Biol.&Genetics, Assist.Prof., 遺伝子実験施設, 助手 (50212220)
SUGAWA Hideo  Kyoto Univ., Dept.of Labo.Med.Lecturer, 医学部, 講師 (70162857)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsimmunoglobulin genes / Anti-TSH receptor antibodies / TSH receptor, / Thyrotropin / Graves'disease, / Hypothyroidism / Myxedema / Autoantibodies
Research Abstract

To elucidate the etiological aspects of autoimmune diseases, we aimed to study immunogloblin genes encoding autoantibodies, anti-TSH receptor antibodies. We prepared EB virus transformed B lymphocytes producing anti-TSH receptor antibodies from peripheral blood lymphocytes of patients with Graves' disease and primary hypothyroidism. Variable regions of immunoglobulin genes of these lymphocytes were isolated and sequenced. We obtained following findings :
1) Repertoires of immunoglobulin variable genes were investigated and their restricted usage were found both in heavy and light chains.
2) Sequence analysis revealed that a number of replacement (R) and silent (S) somatic mutations were found both in CDR and framework and the R/S ratios of CDR tended to be higher than those of the framework, suggesting the importance of somatic mutations for antibodies activities.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Snin EK.,Matsuda F.,Fujikura J.,Akamizu T.,Sugawa H,Mori T.,Honjo T: "Cloning of a human immunoglobulin gene fragment containing both VH-D and D-JH rearrangements:implication for VH-D as an intermediate to VH-D-JH formation." Europ J Immunol. 23. 2365-2367 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shin EK.,Akamizu T.,Sugawa H.,Matsuda F.,Fujikura J.,Mori T.,Honjo: "Variable-regions of immunoglobulin heavy-chain genes encoding anti-thyrotropin(TSH)receptor antibodies of patients with graves disease." J Immunol. 152. 1485-1492 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okuda J.,Akamizu T.,Sugawa H.,Matsuda F.,Li H.,Mori T: "Preparation and characterization of monoclonal antithyrotropin receptor antibodies(TSH-R Ab)obtained from periforal lymphocytes of hypothyroid patients with primary myxedema." J Clin Endocrinol Metab. 79. 1600-1604 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura N.,Azuma C.,Akamuzu T.,Sugawa H.,Matsuda F.,Mitsuda N.,Honjo T.,Mori T.,Yamaji K: "Heterogeneity and diversity of IgM and IgG lupus anticoagulants in a individual with systemic lupus erythematosus." Biochem Biophys Rec Commun. 203. 1789-1794 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Li H.,Akamizu T.,Okuda J.,Sugawa H.,Matsuda F.,Tsubata T.,Mori T: "Isolation of Epstein-Barr virus-transformed lymphocytes producing lgG class monoclonal antibodies using a Magnetic Cell Separator (MACS):Preparation of thyroid-stimulating lgG antibodies from patients with Graves disease." Biochem Biophys Res Commun.207. 985 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 松田文彦: "甲状腺疾患の分子免疫内分泌学「TSHレセプター抗体のVH遺伝子の構造」" 日本臨床, 5 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 赤水尚史、森 徹: "抗TSHレセプター抗体の免疫グロブリン遺伝子について" ホルモンと臨床, 6 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shin EK,Matsuda F,Fujikura J,Akamizu T,Sugawa H,Mori T,Honjo T: "Cloning of a human immunoglobulin gene fragment containing both VH-D and D-JH rearrangements : implication for VH-D as an intermediate to VH-D-JH formation." Europ J Immunol. 23. 2365-2367 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shin EK,Akamizu T,Sugawa H,Matsuda F,Fujikura J,Mori T,Honjo: "Variable-regions of immunoglobulin heavy-chain genes encoding anti-thyrotropin (TSH) reseptor antibodies of patients with graves'disease." J Immunol. 152. 1485-1492 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okuda J,Akamizu T,Sugawa H,Matusda F,Li H,Mori T: "Preparation and characterization of monoclonal antithyrotropin receptor antibodies (TSH-R Ab) obtained from periferal lymphocytes of hypothyroid patients with primary myxedema." J Clin Endocrinol Metab. 79. 1600-1604 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura N,Azuma C,Akamuzu T,Sugawa H,Matsuda F,Mitsuda N,Honjo T,Mori T,Yamaji K: "Heterogeneity and diversity of IgM and IgG lupus anticoagulants in an individual with systemic lupus erythematosus." Biochem Biophys Res Commun. 203. 1789-1794 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Li H,Akamizu T,Okuda J,Sugawa H,Matsuda F,Tsubata T,Mori T: "Isolation of Epstein-Barr virus-transformed lymphocytes producing IgG class monoclonal antibodies using a Magnetic Cell Separator (MACS) : Preparation of thyroid-stimulating IgG antibodies from patients with Graves'disease." Biochem Biophys Res Commun. 207. 985 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shin EX. Matsuda F. Fujikura J. Akamizu T. Sugawa H. Mori T. Honjo T: "Cloning of a human immunoglobulin gene fragment containing both VH-D and D-JH rearrangements: implication for VH-D as an intermediate to VH-D-JH formation." Europ J Immunol.23. 2365-2367 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shin EX. Akamizu T. Sugawa H. Matsuda F. Fujikura J. Mori T. Honjo: "Variable-regions of immunoglobulin heavy-chain genes encoding antithyrotropin (TSH) receptor antibodies of patients with graves' diseasc." J Immunol.152. 1485-1492 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okuda J. Akamizu T. Sugawa H. Matsuda F. Li H. Mori T: "Preparation and characterization of monoclonal antithyrotropin receptor antibodies (TSH-R Ab) obtained from periferal lymphocytes of hypothyroid patients with primary myxedema." J Clin Endocrinol Metab. 79. 1600-1604 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakamura N. Azuma C. Akamuzu T. Sugawa H. Matsuda F. Mitsuda N. Honjo T. Mori T. Yamaji K.: "Heterogeneity and diversity of 1gM and 1gG lupus anticoagulants in an individual with systemic lupus erythematosus." Biochem Biophys Res Commun. 203. 1789-1794 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Li H. Akamizu T. Okuda J. Sugawa H. Matsuda F. Tsubata T. Mori T.: "Isolation of Epstein-Barr virus-transformed lymphocytes producing 1gG class monoclonal antibodies using a Magnetic cell Separator (MACS): Preparation of thyroid-stimulating 1gG antibodies from patients with Graves'disease." Biochem Biophys Res Commun. 207. 985- (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松田文彦: "甲状腺疾患の分子免疫内分泌学「TSHレセプター抗体のVH遺伝子の構造」" 日本臨床, 5 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 赤水尚史、森 徹: "抗TSHレセプター抗体の免疫グロブリン遺伝子について。" ホルモンと臨床, 6 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shin E.K: "Variable-regions of immunoglobulin heavy-chain gene encoding anti-thyrotropin (TSH) receptor antibodies of patients with Graves' disease." Journal of Immunology. 152. 1485-1492 (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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