Pathogenesis of autoantibodies against prothrombin

• Project/Area Number: 22591074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Hokkaido 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: ¥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 / ﾙｰﾌﾟｽｱﾝﾁｺｱｸﾞﾗﾝﾄ / 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.

Research Products

• [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 (2013)
  • Author(s): Kamishima T, Kato M, Atsumi T, Koike T, Onodera Y, Terae S
  • Journal Title: ClinExp Rheumatol Volume: 31(1) Pages: 154-154
  • 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
  • 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 DMARDs (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Amerged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study (2013)
  • 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
  • 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 Rheumatology (2013)
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Phospholipid scramblase 1 expression is enhanced in patients with antiphospholipid syndrome (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Predominant prevalence of arterial thrombosis in Japanese patients with antiphospholipid (2012)
  • 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
  • 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, 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
  • Peer Reviewed
• [Journal Article] Factor XI is a substrate for oxidoreductases: enhanced activation of reduced FXI and its role in antiphospholipid syndrome thrombosis (2012)
  • 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
  • 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 arthritis (2012)
  • 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: 64(8) Issue: 11 Pages: 1125-34
  • DOI: 10.1136/annrheumdis-2011-200838
  • Peer Reviewed
• [Journal Article] Impaired expression of Act1mRNA in B cells of patients with Sjogren's syndrome (2012)
  • 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
  • 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 autoantibodies (2012)
  • 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
  • Peer Reviewed
• [Journal Article] The efficacy of antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events (2012)
  • 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
  • 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 joint (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of cigarette smoking and systemic lupus erythematosus in a Japanese population (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Thrombotic microangiopathy due to multiple autoantibodies related to antiphospholipid syndrome (2012)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Cigarette Smoking, Alcohol Consumption, and Risk of Systemic Lupus Erythematosus: A Case-control Study in a JapanesePopulation (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome (2012)
  • 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
  • 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
  • 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 arthritis. (2012)
  • Author(s): Sakai R
  • Journal Title: Arthritis Care Res Volume: 64 Issue: 8 Pages: 1125-1134
  • DOI: 10.1002/acr.21666
  • 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
  • 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 joint (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis : the JMAAV study (2011)
  • 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
  • Peer Reviewed
• [Journal Article] The efficacy of Antiphospholipid Score for the diagnosis of antiphospholipid syndrome and its oredictive value for thrombotic events (2011)
  • Author(s): Otomo K, Atsumi T, Amengual O, et al.
  • Journal Title: Arthritis Rheum Volume: 64 Pages: 504-512
  • Peer Reviewed
• [Journal Article] Pathophysiology of thrombosis and potential targeted therapies in antiphospholipid syndrome (2011)
  • Author(s): Amengual O, Atsumi T, Koike
  • Journal Title: Current Vascular Pharacology Volume: 9 Pages: 606-618
  • 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 I (2011)
  • Author(s): Ioannou Y, Zhang JY, Qi M, Atsumi T, et al.
  • Journal Title: Arthritis Rheum Volume: 63 Pages: 277-282
  • 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
  • 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
  • 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
  • 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)
  • 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)
  • 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)
  • Invited
• [Presentation] How should we diagnose/classify the antiphospholipid syndrome (2011)
  • 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)
• [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
• [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
• [Book] 抗リン脂質抗体症候群 (2013)
  • Author(s): 渥美達也
  • Publisher: 南江堂
• [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
• [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
• [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
• [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
• [Book] EBM血液疾患の治療2013-2014 (2012)
  • Author(s): 藤枝雄一郎
  • Total Pages: 594
  • Publisher: 中外医学社
• [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
• [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