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The Analysis for Human Autoantibody Producing System using Biotechnology.

Research Project

Project/Area Number 01480214
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionTohoku University

Principal Investigator

SASAKI Takeshi  2nd Department of Internal Medicine, Tohoku University School of Medicine, Associate Professor, 医学部, 助教授 (50110656)

Co-Investigator(Kenkyū-buntansha) SANO Hiroshi  Biotechnology Instutute, Akita Prefectural College of Agriculture, Professor, 生物工学研究所, 教授 (20178809)
ENDO Kazuyasu  2nd Department of Internal Medicine, Tohoku University School of Medicine, Instr, 医学部付属病院, 講師 (60125507)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1989: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsAutoantibody / Anti-DNA Antibody / Immunoglobulin Gene / Systemic Lupus Erythematosus / 抗DMA抗体 / In situ ハイブリダイゼ-ション / 抗DNA抗体
Research Abstract

1. We identified specific clonotypes expressing anti-DNA idiotypes (0-81 Id and NE-1 Id) in circulating immune complexes (CIC) of patients with active lupus nephritis. Isoelectrofocusing studies revealed that renal elevates formed three bands with DNA, in which one was identical with that of CIC-derived antibodies. Positive tests for anti-DNA CIC were significantly associated with the incidence of diffuse proliferative glomerulonephritis (DPGN).
2. The analysis of B cell repertoire in patients with SLE revealed that nephritogenic 0-81 Id- or NE-1-Id-positive clones at precursor level tended to increase in lupus patients. DNA sequences coding the variable regions of anti-DNA clones, NE-l and NE-13 were identical with the germline gene, VH4.21, and Vk gene segments with Vk21b. These data indicates that antigen-driven somatic mutations may have no important role to play in the expansion of some IgM clones associated with pathogenetic anti-DNA Ab in SLE.
3. We studied VH gene family usages on B cells from patients with SLE. Dot blot hybridization and northern blot analysis revealed that the SLE B cells may preferentially use VH I and VH IV, which often encode autoantibodies with polyspecificity. We also developed in situ hybridization technique for the detection of VH gene at clonal level.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] T.Sasaki,A.Hatakeyama,S.Shibata,H.Osaki,M.Suzuki,K.Horie,Y.Kitagawa,K.Yoshinaga: "Heterogeneity of immune complex-derived anti-DNA antibodies associated with lupus nephritis." Kidney International. 39. 746-753 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N.Harata,T.Sasaki,S.Shibata,J.Kameoka,Y.Hirabayashi,H.Osaki,E.Tamate,K.Yoshinaga: "Selective absorption of anti-DNA antibodies and their idiotype-positive cells in vitro using an antiidiotypic antibody-affinity column,possible application to plasmaexchange." J.Clinical Apheresis. 6. 34-39 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Sasaki: "Anti-DNA idiotypes and anti-idiotypes in systemic lupus erythematosus." Jpn.J.Med.19. 655-656 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Suzuki,A.Hatakeyama,E.Tamate,T.Kurosawa,T.Saito,T.Sasaki,K.Yoshinaga: "Anti-DNA idiotypes deposited in the renal glomeruli of patients with lupus nephritis." Am.J.Kidney Dis.18. 232-239 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H.Shiraishi,M.Nakamura,N.Yaegashi,T.Sasaki,K.Sugamura: "Laboratory infection of HPV/B19・" J.Infection. 22. 308-310 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Sasaki,T.Muryoi,A.Hatakeyama,M.Suzuki,T.Seino,T.Saito,K.Yoshinaga: "Circulating immune complexes in active lupus nephritis." Am.J.Med.91. 355-362 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K. Itoi, T. Sasaki, T. Sawai, M. Nakamura, N. Hiwatashi, T. Muryoi, . . Yokoyama, K. Yoshinaga: "Protein-Losing Gastroenteropathy in Association with Immune Deposits in Gastrointestinal Mucosal Capillaries." Amer. J. Gastroent.84. 187-191 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Sasaki, E. Tamate, T. Muryoi, O. Takai, K. Yoshinaga.: "In vitro Manipulation of Human Anti-DNA Antibody Production by Anti-Idiotypic Antibodies Conjugated with Neocarzinostatin." J. Immunology. 142. 1159-1165 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sano, O. Takai, N. Harata, I. Kodama, T. Sasaki, K. Yoshinaga: "Binding Properties of Human Anti-DNA Antibodies to Cloned Human DNA Fragments." Scand. J. Immunol.30. 51-60 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] C. Murai, T. Sasaki, H. Osaki, A. Hatakeyama, S. Shibata, K. Yoshinaga.: "Oral Limaprot for Raynaud's Phenomenon." Lancet. II. 1218 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] O. Takai, T. Sasaki, T. Muryoi, H. Hashimoto, K. Yoshinaga.: "Incidence of Anti-DNA Idiotype-Positive Cells in Human Peripheral Blood." J. Clin. Immunol.9. 313-321 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Sasaki, Y. Koide, K. Yoshinaga.: "Immune Suppression of Anti-DNA Antibody Production Using Anti-Idiotypic Antibody-Neocarzinostatin Conjugates." Methods in Enzymology. 178. 422-432 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Muryoi, T. Sasaki, Y. Sekiguchi, E. Tamate, O. Takai. K. Yoshinaga.: "Impaired Accessory Cell Function of Monocytes in Systemic Lupus Erythematosus." J. Clin. Lab. Immunol.28. 123-128 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Sasaki, S. Shibata, Y. Hirabayashi, Y. Sekiguchi. K. Yoshinaga.: "Accessory Cell Activity of Monocytes in Anti-DNA Antibody Production in Systemic Lupus Erythematosus." Clin. Exp. Immunol. 77. 37-42 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Sasaki, S. Shibata, N. Harata E. Tamate, K. Yoshinaga.: "Idiotype Network and Anti-DNA Antibody Production." Mol. Cell Bio. Autoantibodies, Autoimmunity.79-80 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Muryoi, T. Sasaki, A. Hatakeyama, S. Shibata, M. Suzuki, J. Seino, K. Yoshinaga.: "Clonotypes of Anti-DNA Antibodies Expressing Specific Idiotypes in Immune Complexes of Patients with Active Lupus Nephritis." J. Immunology. 144. 3856-3861 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] A. Hatakeyama, T. Sasaki, T. Muryoi, C. Murai, K. Yoshinaga: "Are the Clonotypes of Serum JgG Anti-DNA Antibodies Associated with Lupus Nephritis in Humans?" Tohoku J. Exp. Med.(1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N. Harata, T. Sasaki, H. Osaki, T. Saito, S. Shibata, T. Muryoi, O. Takai, K. Yoshinaga.: "Therapeutic Treatment of New Zealand Mice Disease by a Limited Number of Anti-Idiotypic Antibodies Conjugated with Neocarzinostatin." J. Clin. Invest.86. 769-776 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N. Harata, T. Sasaki, S. Shibata, J. Kameoka, Y. Hirabayashi, H. Osaki, E. Tamate, K. Yoshinaga: "Selective Absorption of Anti-DNA Antibodies and Their Idiotypepositive Cells in Vitro Using an Antiidiotypic Antibodyaffinity Column, Possible Application to Plasmaexchange." J. Clinical Apheresis. 6. 34-39 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Sasaki, T. Myryoi, A. Hatakeyama, M. Suzuki, T. Seino, T. Saito, K. Yoshinaga: "Circulating Immune Complexes in Active Lupus Nephritis." Am. J. Med.91. 355-362 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Suzuki, A. Hatakeyama, E. Tamate, T. Kurosawa, T. Saito T. Sasaki, K. Yoshinaga: "Anti-DNA Idiotypes Deposited in the Renal Glomcruli of Patients with Lupus Nephritis." Am. J. Kidney Dis.18. 232-239 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Sasaki, A. Hatakeyama, S. Shibata, H. Osaki, M. Suzuki, K. Horie, Y. Kitagawa, K. Yoshinaga: "Heterogeneity of Immune Complex-Derived Anti DNA Antibodies Associated with Lupus Nephritis." Kidney International. 39. 746-753 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Shiraishi, M. Nakamura, N. Yaegashi, T. Sasaki, K. Sugamura: "Laboratory infection of HPV/Bly" J. Infection. 22. 308-310 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Sasaki: "Anti-DNA Idiotypes and Anti-Idiotypes in Systemic Lupus Erythematosus." Jpn. J. Med.19. 655-656 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Muryoi, K. N. Kasturi, M. Kafina, D. S. Cram, C. C. Harrison, T. Sasaki, C. A. Bona: "Anti-Topoisomerose 1 Monoclonal Antibodies from Scleroderma Patients and Tight Skin Mouse Interact with Similar Epitopes" J. Exp. Med.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Hirabayashi, T. Sasaki, S. Shibata, H. Osaki, Munakata, H. Sano, K. Yoshinaga: "The Variable Regions of Human Anti-DNA Antibodies Expressing Cross-Reactive Idiotypes are Encoded by Gernline VH and VL Genes." Arth. Rheum.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S. Shibata, T. Sasaki, Y. Hirabayashi, J. Seino, K. Okamura, K. Yoshinaga, et al.: "Risk Factors in Pregnancy of Patients in Systemic Lupus Erythematosus -Hypocomplementemia is Associated with" Ann. Rheum. Dis.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Ohsaki, T. Sasaki, A. Hatakeyama, M. Nose, K. Yoshinaga: "Hypersensitivity Angitis in an Adult with Rubella Infection." J. Rheumatology. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S. Shibata, T. Sasaki, A. Hatakeyama, Y. Munakata, Y. Hirabayashi, K. Yoshinaga: "Clonal Frequency Analysis of B Cells Producing Pathogeanti-DNA Antibody-Associated Idiotypes in Systemic Lupus Erythematosus" Clin. Immunol. Immunopath.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Ohteki, T. Abe, A. Kugami, T. Sasaki, S. Shibata, S. Seki,: "Age-associated Increase of the Most Primitive CDS+B Cells in the Liver of Autoimmune NAB/W F1 Mice" J. Immunol.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Sasaki,A.Hatakeyama,S.Shibata,H.Osaki,M.Suzuki,K.Horie,Y.Kitagawa,K.Yoshinaga: "Heterogeneity of immune complexーderived antiーDNA antibodies associated with lupus nephritis." Kidney International. 39. 746-753 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] N.Harata,T.Sasaki,S.Shibata,J.Kameoka,Y.Hirabayashi,H.Osaki,E.Tamate,K.Yoshinaga: "Selective absorption of antiーDNA antibodies and their idiotypeーpositive cells in vitro using an antiidiotypic antibodyーaffinity column,possible application to plasmaexchange." J.Clinical Apheresis. 6. 34-39 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Sasaki: "AntiーDNA idiotypes and antiーidiotypes in systemic lupus erythematosus." Jpn.J.Med.19. 655-656 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Suzuki,A.Hatakeyama,E.Tamate,T.Kurosawa,T.Saito,T.Sasaki,K.Yoshinaga: "AntiーDNA idiotypes deposited in the renal glomeruli of patients with lupus nephritis." Am.J.Kidney Dis.18. 232-239 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Shiraishi,M.Nakamura,N.Yaegashi,T.Sasaki,K.Sugamura: "Laboratory infection of HPV/B19." J.Infection. 22. 308-310 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Sasaki,T.Muryoi,A.Hatakeyama,M.Suzuki,T.Seino,T.Saito,K.Yoshinaga: "Circulating immune complexes in active lupus nephritis." Am.J.Med.91. 355-362 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Muryoi T,<Sasaki T>___ー,Hatakeyama A,Shibata S,Suzuki M,Seino J and Yoshinaga K.: "Clonotypes of antiーDNA antibodies expressing specific idiotypes in immune complexes of patients with active lupus nephritis." J.Immunology. 144. 3856-3861 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hatakeyama A,<Sasaki T>___ー,Muryoi T,Murai C and Yoshinaga K.: "Are the clonotypes of serum IgG antiーDNA antibodies associated with lupus nephritis in humans?" Tohoku J.Exp.Med.160. 213-221 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Harata N,<Sasaki T>___ー,Osaki H,Saito Y,Shibata S,Muryoi T,Takai O and Yoshinaga K.: "Therapeutic treatment of New Zealand mouse disease by a limited number of antiーidiotypic antibodies conjugated with neocarzinostatin." J.Clin.Invest.86. 769-776 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] <Sasaki T>___ー,Hatakeyama A,Shibata S,Osaki H,Suzuki M,Horie K,Kitagawa Y and Yoshinaga K.: "Heterogeneity of immune complexーderived antiーDNA antibodies associated with lupus nephritis." Kidney International. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Harata N,<Sasaki T>___ー,Shibata S,Kameoka J,Hirabayashi Y,Osaki H,Tamate E and Yoshinaga K.: "Selective absorption of antiーDNA antibodies and their idiotypeーpositive cells in vitro using an antiーidiotypic antibodyーaffinity column,possible application to plasma exhange." Journal of Clinical Apheresis. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] <Sasaki T.>___ー: "AntiーDNA idiotypes and antiーidiotypes in systemic lupus erythematosus." Jpn.J.Med.19. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Sasaki,E,Tamate,T.Muryoi,O.Takai and K.Yoshinaga: "In vitro manipulation of human anti-DNA antibody produc-tion by anti-idiotypic antibodies conjugated with neocarzinostatin." Jounal of Immunology. 142. 1159-1989 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Sano O.Takai,N.Harata K.Yoshinaga,I.Kodama and T.Sasaki: "Binding properties of human anti-DNA antibodies to cloned human DNA fragments." Scandinavian Journal of Immunology. 30. 51-60 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Sasaki,Takahashi,Y.Yoshinaga,K.Sugamura and H.Shiraishi: "An association between parvovirus B-19 infection and autoantibody production" Journal of Rheumatology. 16. 708-709 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Sasaki,S.Shibata,Y.Hirabayashi,Y.Sekiguchi and K.Yoshinaga: "Accessory cell activity of monocytes in anti-DNA antibody production in systemic lupus erythematosus." Clinical Experimental Immunology. 77. 37-42 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] C.Murai,T.Sasaki,Osaki Hatakeyama and K.Yoshinaga: "Oral limaprost for Raynaud's phenomenon" Lancet. II. 1218 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Itoi,T.Sasaki,Sawai,M.Nakamura,N.Hiwatashi Muryoi, and Yoshinaga: "Protein-losing gastroenteropathy in association with immune deposits in gastrointestinal mucosal cappilaries." Ameriacan Journal of Gastroenterology. 84. 187-191 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Sasaki: "Methods in Enzymology,178" Academic Press., 9 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 佐々木毅: "最新医学" 最新医学社, 6 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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