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Pathogenesis of autoantibodies against prothrombin

Research Project

Project/Area Number 22591074
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionHokkaido University

Principal Investigator

ATSUMI Tatsuya  北海道大学, 大学院・医学研究科, 教授 (20301905)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords抗リン脂質抗体 / 血栓症 / 自己免疫 / ループスアンチコアグラント / ループスアンチコアグラント / 自己抗体 / 抗リン脂質抗体症候群 / 単球 / 質量分析 / プロテオーム
Research Abstract

The aim of this research was to clarify how autoantibodies against prothrombin, one of the major markers of antiphosholipid syndrome(APS), are related with thrombophilia in patients with APS. The antiprothrombin antibodies affected endothelial cells or monocytes, leading to the over-expression of procoagulant substances. In this procedure, ribopholin II, precent on cell surface, was likely to be involved as a receptor ofprothrombin molecule.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (48 results)

All 2013 2012 2011 2010 Other

All Journal Article (36 results) (of which Peer Reviewed: 36 results) Presentation (4 results) (of which Invited: 1 results) Book (8 results)

  • [Journal Article] Contrast-enhanced whole body joint MR Imaging in rheumatoid patients on tumour necrosis factor-alpha agents: a pilot study to evaluate novel scoring system for MR synovitis2013

    • Author(s)
      Kamishima T, Kato M, Atsumi T, Koike T, Onodera Y, Terae S
    • Journal Title

      ClinExp Rheumatol

      Volume: 31(1) Pages: 154-154

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of TNF-α-converting enzyme in fibroblasts augments dermal fibrosis after inflammation.2013

    • Author(s)
      Fukaya S
    • Journal Title

      Lab Invest.

      Volume: 93 Issue: 1 Pages: 72-80

    • DOI

      10.1038/labinvest.2012.153

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Elevation of KL-6 serum levels in clinical trials of tumor necrosis factor inhibitors in patients withrheumatoid arthritis: a report from the Japan College of Rheumatology Ad Hoc Committee for Safety of Biological DMARDs2013

    • Author(s)
      Harigai M, Takamura A, Atsumi T, Dohi M, Hirata S, Kameda H, Nagasawa H, Seto Y, Koike T, Miyasaka N
    • Journal Title

      Mod Rheumatol

      Volume: 23(2) Issue: 2 Pages: 284-96

    • DOI

      10.1007/s10165-012-0657-2

    • NAID

      10031167700

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Amerged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study2013

    • Author(s)
      Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T
    • Journal Title

      Ann Rheum Dis

      Volume: 72 Issue: 2 Pages: 310-2

    • DOI

      10.1136/annrheumdis-2012-201804

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A retrospective study of serum KL-6 levels during treatment with biological disease-modifyingantirheumatic drugs in rheumatoid arthritis patients: a report from the Ad Hoc Committee for Safety of Biological DMARDs of the Japan College of Rheumatology2013

    • Author(s)
      Takamura A, Hirata S, Nagasawa H, Kameda H, Seto Y, Atsumi T, Dohi M, Koike T, Miyasaka N, Harugau M
    • Journal Title

      Mod Rheumatol

      Volume: 23(2) Issue: 2 Pages: 297-303

    • DOI

      10.1007/s10165-012-0658-1

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of TNF-α-converting enzyme in fibroblasts augments dermal fibrosis after inflammation.2013

    • Author(s)
      Fukaya S
    • Journal Title

      Lab Invest

      Volume: 93 Pages: 72-80

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of the p38 mitogen-activated protein kinase pathway in the tissue factor gene expression by the phosphatidylserine-dependent antiprothrombin antibody factor gene expression by the phosphatidylserine-dependent antiprothrombin antibody.2013

    • Author(s)
      Oku K
    • Journal Title

      Rheumatol

      Volume: in press

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The involvement of CD36 in the monocyte activation by antiphospholipid antibodies.2013

    • Author(s)
      Kato M
    • Journal Title

      Lupus

      Volume: in press

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phospholipid scramblase 1 expression is enhanced in patients with antiphospholipid syndrome2012

    • Author(s)
      Amengual O, Atsumi T, Oku K, Suzuki E, Horita T, Yasuda S, Koike T
    • Journal Title

      Mod Rheumatol

      Volume: 23(1) Issue: 1 Pages: 81-8

    • DOI

      10.1007/s10165-012-0642-9

    • NAID

      10031167669

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Predominant prevalence of arterial thrombosis in Japanese patients with antiphospholipid2012

    • Author(s)
      Fujieda Y, Atsumi T, Amengual O, Odani T, Otomo K, Kato M, Oku K, Kon Y, Horita T, Yasuda S, Koike T
    • Journal Title

      syndromeLupus

      Volume: 21(14) Issue: 14 Pages: 1506-14

    • DOI

      10.1177/0961203312458469

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulated expression of HLA-DRB5 transcripts and high frequency of the HLA-DRB5*01:05 allele in scleroderma patients with interstitial lung disease2012

    • Author(s)
      Odani T, Yasuda S, Ota Y, Fujieda Y, Kon Y, Horita T, Kawaguchi Y, Atsumi T, Yamanaka H, Koike T
    • Journal Title

      Rheumatology(Oxford)

      Volume: 51(10) Pages: 1765-74

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Factor XI is a substrate for oxidoreductases: enhanced activation of reduced FXI and its role in antiphospholipid syndrome thrombosis2012

    • Author(s)
      Giannakopoulod B, Gao L, Qi M, Wong JW, Yu DM, Vlachoyiannopoulos PG, Moutsopoulos HM, Atsumi T, Koike T, Hogg P, Qi JC, Krilis SA
    • Journal Title

      J Autoimmun

      Volume: 39(3) Issue: 3 Pages: 121-9

    • DOI

      10.1016/j.jaut.2012.05.005

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules2012

    • Author(s)
      Sakai R, Komano Y, Tanaka M, Nanki T, Koike R, Nagasawa H, Amano K,Nakajima A, Atsumi T, Koike T, Ihata A, Ishigatsubo Y, Saito K,Tanaka Y, Ito S, Sumida T, Tohma S,Tamura N, Fujii T, Sugihara T, Kawakami A, Hagino N, Ueki Y, Hashiramoto A, Nagasawa K,Miyasaka N, Harigai M
    • Journal Title

      Arthritis Care Res

      Volume: 71 Issue: 11 Pages: 1820

    • DOI

      10.1136/annrheumdis-2011-200838

    • NAID

      120006985490

    • URL

      https://pure.teikyo.jp/en/publications/3970fbcf-802b-43fa-b286-5e590ceb9904

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired expression of Act1mRNA in B cells of patients with Sjogren's syndrome2012

    • Author(s)
      Nakagawa Y, Kataoka H, Kurita T, Nakagawa H, Yasuda S, Horita T, Atsumi T, Koike T
    • Journal Title

      Nihon Rinsho Meneki Gakkai Kaishi

      Volume: 35(1) Pages: 75-80

    • NAID

      10030465739

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A case of catastrophic antiphospholipid antibody syndrome complicated with systemic lupus erythematosus, double positive for anti-cardiolipin/β(2) glycoprotei I and anti-phosphatidylserine/prothrombin autoantibodies2012

    • Author(s)
      Hirakawa E, Saito K, Hirata S, Atsumi T, Koike T, Tanaka Y
    • Journal Title

      Mod Rheumatol

      Volume: 22(5) Issue: 5 Pages: 769-73

    • DOI

      10.1007/s10165-011-0563-z

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The efficacy of antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events2012

    • Author(s)
      Otomo K, Atsumi T, Amengual O, Fujieda Y, Kato M, Oku K, Horita T, Yasuda S, Koike T
    • Journal Title

      Arthritis Rheum

      Volume: 64 Issue: 2 Pages: 504-512

    • DOI

      10.1002/art.33340

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Positive synovial vascularity in patients with low disease activity indicates smouldering inflammation leading to joint damage in rheumatoid arthritis: time-integrated joint inflammation estimated by synovial vascularity in each finger joint2012

    • Author(s)
      Fukae J, Isobe M, Kitano A, Henmi M, Sakamoto F, Narita A, Ito T, Mitsuzaki A, Shimizu M, Tanimura K, Matsuhashi M, Kamishima T, Atsumi T, Koike T.
    • Journal Title

      Rheumatology

      Volume: 52(3) Pages: 523-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of cigarette smoking and systemic lupus erythematosus in a Japanese population2012

    • Author(s)
      Kiyohara C, Washio M, Horiuchi T, Asami T, et al.
    • Journal Title

      Scand J Rheumatol

      Volume: 41 Issue: 2 Pages: 103-109

    • DOI

      10.3109/03009742.2011.608194

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thrombotic microangiopathy due to multiple autoantibodies related to antiphospholipid syndrome2012

    • Author(s)
      Noda S, Ogura M, Tsutsumi A, Udagawa T, Kamei K, Matsuoka K, Kitamura H, Atsumi T, Ito S
    • Journal Title

      Pediatr Nephrol

      Volume: 4 Issue: 4 Pages: 681-5

    • DOI

      10.1007/s00467-011-2085-5

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Management of resolved hepatitis B in patients with low anti-hepatitis B surface titer who undergo aggressive immunosuppressive therapy: reply to the letter by Mori.2012

    • Author(s)
      Kato M, Atsumi T
    • Journal Title

      J Rheumatol

      Volume: 39 Issue: 6 Pages: 1293-4

    • DOI

      10.3899/jrheum.120117

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese2012

    • Author(s)
      岡田随象
    • Journal Title

      PLoS Genetics

      Volume: (掲載確定) Issue: 1 Pages: 1002455-1002455

    • DOI

      10.1371/journal.pgen.1002455

    • NAID

      120005906866

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cigarette Smoking, Alcohol Consumption, and Risk of Systemic Lupus Erythematosus: A Case-control Study in a JapanesePopulation2012

    • Author(s)
      Kiyohara C, Washio M, Horiuchi T, Asami T, Ide S, Atsumi T, Kobashi G, Tada Y, Takahashi H
    • Journal Title

      J Rheumatol

      Volume: 39 Issue: 7 Pages: 1363-70

    • DOI

      10.3899/jrheum.111609

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome2012

    • Author(s)
      Oku K, Amengual O, Atsumi T
    • Journal Title

      Eur J Clin Invest

      Volume: 42 Issue: 10 Pages: 1126-35

    • DOI

      10.1111/j.1365-2362.2012.02697.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulated expression of HLA-DRB5 transcripts and high frequency of the HLA-DRB5*01:05 allele in scleroderma patients with interstitial lung disease.2012

    • Author(s)
      Odani T
    • Journal Title

      Rheumatology

      Volume: 51 Pages: 1765-1774

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time-dependent increased risk for serious infection from continuous use of tumor necrosis factor antagonists over three years in patients with rheumatoid arthritis2012

    • Author(s)
      Sakai R
    • Journal Title

      Arthritis Care Res

      Volume: 64 Issue: 8 Pages: 1125

    • DOI

      10.1002/acr.21666

    • URL

      https://pure.teikyo.jp/en/publications/361c0cff-5aa7-4cc8-ad1d-b4d53cf4fdf6

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contrast-enhanced whole body joint MR Imaging in rheumatoid patients on tumour necrosis factor-alpha agents: a pilot study to evaluate novel scoring system for MR synovitis.2012

    • Author(s)
      Kamishima T
    • Journal Title

      Clin Exp Rheumatol

      Volume: 31 Pages: 154-154

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Positive synovial vascularity in patients with low disease activity indicates smouldering inflammation leading to joint damage in rheumatoid arthritis: time-integrated joint inflammation estimated by synovialvascularity in each finger joint2012

    • Author(s)
      Fukae J, Isobe M, Kitano A, Henmi M, Sakamoto F, Narita A, Ito T, Mitsuzaki A, Shimizu M, Tanimura K, Matsuhashi M, Kamishima T, Atsumi T, Koike T
    • Journal Title

      Rheumatology

      Volume: 52(3) Issue: 3 Pages: 523-8

    • DOI

      10.1093/rheumatology/kes310

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis : the JMAAV study2011

    • Author(s)
      Ozaki S, Atsumi T, Hayashi T, Ishizu A, Kobayashi S, Kumagai S, Kurihara Y, Kurokawa M, Makino H, Nagafuchi H, Nakabayashi K, Nishimoto N, Suka M, Tomino Y, Yamada H, Yamagata K, Yoshida M, Yumura W
    • Journal Title

      Mod Rheumatol

      Volume: (Epub ahead of print) Issue: 3 Pages: 394-404

    • DOI

      10.1007/s10165-011-0525-5

    • NAID

      10030782228

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The efficacy of Antiphospholipid Score for the diagnosis of antiphospholipid syndrome and its oredictive value for thrombotic events2011

    • Author(s)
      Otomo K, Atsumi T, Amengual O, et al.
    • Journal Title

      Arthritis Rheum

      Volume: 64 Pages: 504-512

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathophysiology of thrombosis and potential targeted therapies in antiphospholipid syndrome2011

    • Author(s)
      Amengual O, Atsumi T, Koike
    • Journal Title

      Current Vascular Pharacology

      Volume: 9 Pages: 606-618

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel assays of thrombogenic pathogenicity for the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen beta2-glycoprotein I2011

    • Author(s)
      Ioannou Y, Zhang JY, Qi M, Atsumi T, et al.
    • Journal Title

      Arthritis Rheum

      Volume: 63 Pages: 277-282

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin.2011

    • Author(s)
      Bohgaki M, Matsumoto M, Atsumi T, et al.
    • Journal Title

      J Cell Mol Med

      Volume: (in press)

    • NAID

      120003660581

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased expression of Phospholipid Scramblase 1 in monocytes from patients with systemic lupus erythematosus.2010

    • Author(s)
      Suzuki E, Amengual O, Atsumi T, et al.
    • Journal Title

      J Rheumatol

      Volume: 37 Pages: 1639-1645

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antiprothrombin antibody : why do we need more assays?2010

    • Author(s)
      Atsumi T, Koike T.
    • Journal Title

      Lupus

      Volume: 19 Pages: 436-439

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of the p38 mitogen-activated protein kinase pathway in the tissue factor gene expression by the phosphatidylserine-dependent antiprothrombin antibody.

    • Author(s)
      Oku K, Amengual O, Zigon P, Horita T, Yasuda S, Atsumi T
    • Journal Title

      Rheumatol

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The involvement of CD36 in the monocyte activation by antiphospholipid antibodies

    • Author(s)
      Kato M, Atsumi T, Oku K, Amengual O, Nakagawa H, Fujieda1 Y, Otomo K, Horita T, Yasuda S, Koike T
    • Journal Title

      Lupus

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Phosphatidylserine dependent antiprothrombin antibodies significance and international standardization.2012

    • Author(s)
      Atsumi T.
    • Organizer
      58th Annual Scientific and Standardization Committee Meeting, International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Liverpool Convention Center(UK)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] How should we diagnose/classify the antiphospholipid syndrome2011

    • Author(s)
      Atsumi T
    • Organizer
      57th Annual Scientific and Standardization Committee Meeting, International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Kyoto International conference sennter (Kyoto, Japan)(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Antiphospholipid antibodies and thrombophilia in the antiphospholipid syndrome.2010

    • Author(s)
      Atsumi T.
    • Organizer
      The 9th International Congress on Systemic Lupus Erythematosus
    • Place of Presentation
      Vancouver Convention Centre, Vancouver, Canada 招待講演
    • Year and Date
      2010-06-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Phosphatidylserine dependent antiprothrombin antibodiessignificance and international standardization.2010

    • Author(s)
      Atsumi T.
    • Organizer
      58th Annual Scientific andStandardization Committee Meeting
    • Place of Presentation
      International Society on Thrombosis andHaemostasis, Liverpool
    • Related Report
      2012 Final Research Report
  • [Book] 抗リン脂質抗体症候群2013

    • Author(s)
      渥美達也
    • Publisher
      南江堂
    • Related Report
      2012 Final Research Report
  • [Book] 全身性エリテマトーデス2013

    • Author(s)
      坊垣暁之、渥美達也
    • Publisher
      羊土社
    • Related Report
      2012 Final Research Report
  • [Book] 今日の治療と看護 改訂第3版2013

    • Author(s)
      渥美達也
    • Total Pages
      1467
    • Publisher
      南江堂
    • Related Report
      2012 Annual Research Report
  • [Book] 免疫・アレルギー疾患の分子標的と治療薬事典2013

    • Author(s)
      坊垣暁之
    • Total Pages
      375
    • Publisher
      羊土社
    • Related Report
      2012 Annual Research Report
  • [Book] 抗リン脂質抗体症候群2012

    • Author(s)
      藤枝雄一郎、渥美達也
    • Publisher
      中外医学社
    • Related Report
      2012 Final Research Report
  • [Book] EBM血液疾患の治療2013-20142012

    • Author(s)
      藤枝雄一郎
    • Total Pages
      594
    • Publisher
      中外医学社
    • Related Report
      2012 Annual Research Report
  • [Book] 血栓と止血の臨床(日本血栓止血学会編集)2011

    • Author(s)
      渥美達也
    • Publisher
      南光堂
    • Related Report
      2011 Annual Research Report
  • [Book] Antiphospholipid syndrome : pathogenesis. In : Lahita RG, editor. Systemic Lupus Erythematosus 5th edition.2010

    • Author(s)
      Atsumi T, Amengual O, Koike T
    • Total Pages
      22
    • Publisher
      San Diego : Academic Press
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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