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β2-glycoprotein I gene deficiency (β2GPI-Sapporo) and the progression of atherosclerosis

Research Project

Project/Area Number 12557043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 内科学一般
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KOIKE Takao  Hokkaido Univ., Grad. School of Med., Prof., 大学院・医学研究科, 教授 (80146795)

Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥6,700,000 (Direct Cost: ¥6,700,000)
Keywordsβ2-glycoprotein I / β2GPI Deficiency / β2-GPI-Sapporo / Atherosclerosis / SLE / Risk factor / 抗リン脂質抗体症候 / 血栓症 / β2-GPI / 遺伝子欠損 / LDL / 抗リン脂質抗体症候群
Research Abstract

Recent evidence suggested that antiphospholipid antibodies may have contributed to the formation of atherosclerotic lesions. In SLE less than 45 years of age, myocardial infarction has been recognized as a major cause of mortality. I have reported that aCL found in patients with antiphospholipid syndrome (APS) are not simply directed to the CL structure, but require the presence of β2-glycoprotein I (β2GPI) for bindng and that the epitopes is expressed by conformational changes occurring whenβ2GPI interacts with an oxygen-substituted solid surface. Β2GPI specifically bound to oxidized LDL and oxidized lipoproteins in the blood, especially oxidized LDL, are also sequentially targeted by β2GPI and aCL, and that immunoreaction is involved not only in the metabolism of plasma lipoproteins but also in thrombotic complications accompanied by atherosclerotic events in APS.
Serumβ2GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with completeβ2GPI deficiency were identified. A thymine corresponding to position 379 of the β2GPI cDNA was deleted in every β2GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6.3% in Japanese and none in Caucasians Heterozygotes had significantly lower concentrations of serumβ2GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration ofβ2GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Horita, T., Tsutsumi, A., Takeda, T., Yasuda, S., Takeuti, R., Amasaki, Y., Ichikawa, K., Atsumi, T., Koike, T: "Significance of magnetic resonance imaging in the diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythematosus"Lupus.. 11. 193-196 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Atsumi, T., Koike, T.: "Clinical relevance of antiprothrombin antibodies"Autoimmunity Reviews.1. 1. 49-53 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ieko, M., Nakabayashi, T., Takeda, T., Naitoh, S., Atsumi, T., Koike, T.: "The inhibition of protein C amticoagulamt activity by anti-β2 -glycoprotein I (β2GPI) antibodies isolated from patients with antiphospholipid syndrome by chromatography methods"Mod Rheumatol.. 12. 44-49 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuura, E., Kobayashi, K., Kasahara, J., Yasuda, T., Makino, H., Koike, T., Shoenfeld, Y.: "Anti-β2-glycoprotein I antibodies and atherosclerosis"Int.Rev.Immunol. 21. 51-66 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsumi, A., Atsumi, T., Yamada, H., Hirayama, H, E., Ichikawa, K., Fujimoto, S., Koike T: "Anti-Phosphatidylserine/Prothrombin Antibodies are not Frequently Found in Patients with Unexplained Recurrent Miscarriages"AJRI. 42. 242-244 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tincani, A., Allegri, F., Sanmarco, M., Cinquini, M., Taglieti, M., Balestrieri, G., Koike, T., Ichikawa, K., Meroni, P., Boffa, M.C.: "Antidardiolipin antibody assey : a methodological analysis for a better consensus in routine depterminations"Thromb Haemost.. 86. 575-583 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuti, R., Atsumi, T., Ieko, M., Takeya, H., Yasuda, S., Ichikawa, S., Tsutsumi, A., Suzuki, K., Koike, T: "Coagulation and fibrinolytic activities in 2siblings with β2-glycoprotein I deficiency"Blood. 96:4. 1594-1595 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horita T., Tsutsumi A., Takeda T., Yasuda S., Takeuti R., Amasaki Y., Ichikawa K., Atsumi T., Koike T: "Significance of magnetic resonace imafing in diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythematosus"Lupus. 11. 193-196 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Atsumi T., Koike T.: "Clinical relevance of antiprothrombin antibodies"Autoimmunity Reviews. 1. 49-53 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ieko M., Nakabayashi T., Takeda T., Naitoh S., Atsumi T., Koike T.: "The inhibition of protein C amticoagulamt activity by anti-β2-glycoprotein I(β2GPI)antibodies isolated from patients with antiphospholipid syndrome by chromatography methods"Mod Rheumatol. 12. 44-49 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuura E., Kobayashi K., Kasahara J., Yasuda T., Makino H., Koike T., Shoenfeld Y.: "Anti-β2-glycoprotein I antibodies and atherosclerosis"Int. Rev. Immunol. 21. 51-66 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsumi A., Atsumi T., Yamada H., Hirayama H, E., Ichikawa K., Fujimoto S., Koike T: "Anti-phosohatidylserine/prothrombin antibodies are not frequently found in patients with unexplained recurrent miscarriages"AJRI. 42. 242-244 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tincani A., Allegri F., Sanmarco M., Cinquini M., Taglieti M., Balestrieri G., Koike T., Ichikawa K., Meroni P., Boffa M. C.: "Anticardiolipin antibody assey : a methodological analysis for a better consensus in routine depterminations"Thromb Haemost. 86. 575-583 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuti R., Atsumi T., Ieko M., Takeya H., Yasuda S., Ichikawa S., Tsutsumi A., Suzuki K., Koike T.: "Coagulation and fibrinolytic activities in 2siblings with β2-glycoprotein I deficiency"Blood. 96 : 4. 1594-1595 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horita, T., Tsutsumi, A., Takeda, T., Yasuda, S., Takeuti, R., Amasaki, Y., Ichikawa, K., Atsumi, T., Koike, T: "Significance of magnetic resonace imafing in diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythematosus"Lupus.. 11. 193-196 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Atsumi, T., Koike, T.: "Clinical relevance of antiprothrombin antibodies"Autoimmunity Reviews. 1. 1. 49-53 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ieko, M., Nakabayashi, T., Takeda, T., Naitoh, S., Atsumi, T., Koike, T.: "The inhibition of protein C amticoagulamt activity by anti-β2-glycoprotein I(β2GPI) antibodies isolated from patients with antiphospholipid syndrome by chromatography methods"Mod Rheumatol.. 12. 44-49 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuura, E., Kobayashi, K., Kasahara, J., Yasuda, T., Makino, H., Koike, T., Shoenfeld, Y.: "Anti-β2-glycoprotein I antibodies and atherosclerosis"Int. Rev. Immunol. 21. 51-66 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasuda, S., Tsustumi, A., Astumi, T., Bertolaccini, M.L., Ichikawa, K., Khamashta, M.A., HugesR.V., Koike, T.: "Gene polymorphisms of tissue plasminogen activator and plasminogenactivator inhibitor-1patients with antiphospholipid antibodies"J. Rheumatol. 29:6. 1192-1197 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeuchi, R., Atsumi, T., Ieko, M., Amasaki, Y., Ichikawa, K., Koike, T.: "Supporsed intrinsic fibrinolytic activity by monoclonal anti-beta2 glycoprotein I autantibodies : possible mechanism for thrombosis in patients with antiphospholipid syndrome"Brit J hematol.. 119. 781-788 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小池隆夫, 他221名: "内科学"朝倉書店. 2297 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsutsumi, A.: "Anticardiolipin antibody assey : a methodological analysis for a better consensus in routine depterminations"Thromb Heamost. 86. 575-583 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi, K.: "A specific ligand for b2-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages"J Lipid Research. 42. 697-709 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsumi, A.: "Anti-phosohatidylserine/prothrombin antibodies are not frequently found in patients with unexplained recurrent miscarriages"AJRI.. 42. 242-244 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T., Astumi: "Genetics of antiphopholipid syndrome"Rheumatic disease clinics. 27 : 3. 565-572 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Bertlaccini, M.L.: "Plasma tumor necrosis factor a levels and the -238^* a promoter polymorphism in patients with antiphospholipid syndrome"Thromb Haemost. 85. 198-203 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsustumi, A.: "Mannouse-binding lectin gene : polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome"Hom Metab Res. 33. 317-322 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsumi, A.: "Rheumatic disease clinics of North America"M.A.Khamashta. 176 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小池隆夫: "Heterogeneous behavior anti-β2-glycoprotein."J.Rheumatol.. 72:2. 391-397 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小池隆夫: "Lytic epstein-barr virus infection in the synovial tissue of patients with rheumatoid arthritis."Arthritis.Rheum.. 43:6. 1218-1225 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小池隆夫: "β2-blycoprotein I deficiency : prevalence, genetic background and effects on plasma lipoprotein metabolism and hemostasis."Atherosclerosis.. 152. 337-346 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小池隆夫: "Proteolytic cleavage of β2-glycoprotein I : reduction of antigenicity and the structual relationship."Internal.Immnol.. 12:8. 1183-1192 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小池隆夫: "Association of autoantibodies against the phosphatidyserine-proteronbin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant."Arthritis Rheumatism.. 43:9. 1982-1993 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小池隆夫: "Coagulation and fibrinolytic activities in 2siblings with β2-glycoprotein I deficiency."Blood.. 96:4. 1594-1595 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小池隆夫: "免疫疾患のとらえかた-眼でみるベットサイドの病態生理-"文光堂. 236 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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