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HLA class II complex antibody in recurrent pregnancy loss and pregnancy complications

Research Project

Project/Area Number 17K11235
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKobe University

Principal Investigator

Yamada Hideto  神戸大学, 医学研究科, 非常勤講師 (40220397)

Co-Investigator(Kenkyū-buntansha) 出口 雅士  神戸大学, 医学研究科, 特命教授 (50403291)
谷村 憲司  神戸大学, 医学部附属病院, 准教授 (80593988)
蝦名 康彦  神戸大学, 医学研究科, 医学研究員 (90322809)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords不育症 / 不妊症 / 胎児発育不全 / 妊娠高血圧症候群 / ネオ・セルフ抗体 / 抗リン脂質抗体症候群 / ネオセルフ抗体 / 抗リン脂質抗体 / HLA class II
Outline of Final Research Achievements

The aim of this study was to evaluate association between aβ2GPI/HLA-DR7 complex antibody and recurrent pregnancy loss (RPL), infertility, and pregnancy complications. Fifty-two (22.9%) of 227 women with RPL, 24 (19.8%) of 121 women with unexplained RPL, and 22 (19.3%) of 114 women with APS symptoms but not aPL tested positive for the neo-self antibody. 19% of FGR, 14% of HDP, 8% of premature delivery at 34 or less weeks of gestation, 12% of infertility also tested positive for the antibody. The neo-self antibody may be involved in the pathogenesis of RPL, infertility, as well as pregnancy complications.

Academic Significance and Societal Importance of the Research Achievements

ネオ・セルフ抗体は、不育症、不妊症、産科異常の原因である可能性があることを世界で初めて明らかにした。これまで原因/リスク因子不明とされていた不育症女性の19.8%で陽性になったことから、ネオ・セルフ抗体は、新たな不育症の原因である可能性を示した。また、これまで抗体陽性の不育症で治療した18人では、低用量アスピリンや低用量アスピリン+ヘパリン治療によって、健児を得ている。前向きコホート研究や介入研究の臨床試験によって、因果関係の決定と治療方法の確立が期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (49 results)

All 2021 2020 2019 2018 2017

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 1 results) Presentation (22 results) (of which Int'l Joint Research: 6 results,  Invited: 16 results) Book (10 results)

  • [Journal Article] Neurodevelopmental Outcomes at 18 Months of Corrected Age for Late Preterm Infants Born at 34 and 35 Gestational Weeks2021

    • Author(s)
      Nakasone Ruka、Fujioka Kazumichi、Kyono Yuki、Yoshida Asumi、Kido Takumi、Suga Shutaro、Abe Shinya、Ashina Mariko、Nishida Kosuke、Tanimura Kenji、Yamada Hideto、Nozu Kandai、Iijima Kazumoto
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 2 Pages: 640-640

    • DOI

      10.3390/ijerph18020640

    • NAID

      120006958056

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The beta(2)-Glycoprotein I/HLA-DR Complex As A Major Autoantibody Target in Obstetric Antiphospholipid Syndrome2020

    • Author(s)
      [Kenji Tanimura,Shigeru Saito,Mikiya Nakatsuka,Takeshi Nagamatsu,Tomoyuki Fujii,Atsushi Fukui,Masashi Deguchi,Yuki Sasagawa,Noriko Arase,Hisashi Arase,Hideto Yamada]
    • Journal Title

      ARTHRITIS & RHEUMATOLOGY

      Volume: 72 Issue: 11 Pages: 1882-1891

    • DOI

      10.1002/art.41410

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vaginal microbiota associated with preterm delivery.2020

    • Author(s)
      Shi Y, Tanimura K, Sasagawa Y, Yamada H.
    • Journal Title

      J Infect Chemother

      Volume: 26 Issue: 11 Pages: 1134-1138

    • DOI

      10.1016/j.jiac.2020.06.003

    • NAID

      120006892077

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recurrence of postpartum hemorrhage in women with a history of uterine artery embolization.2020

    • Author(s)
      Imafuku H, Yamada H, Morizane M, Tanimura K.
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 46 Issue: 1 Pages: 119-123

    • DOI

      10.1111/jog.14129

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical factors associated with pregnancy outcome in women with recurrent pregnancy loss2019

    • Author(s)
      Miyaji Maho、Deguchi Masashi、Tanimura Kenji、Sasagawa Yuki、Morizane Mayumi、Ebina Yasuhiko、Yamada Hideto
    • Journal Title

      Gynecological Endocrinology

      Volume: 35 Issue: 10 Pages: 1-6

    • DOI

      10.1080/09513590.2019.1604657

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk Factors and Outcomes of Recurrent Pregnancy Loss in Japan.2019

    • Author(s)
      Morita K, Ono Y, Takeshita T, Sugi T, Fujii T, Yamada H, Nakatsuka M, Fukui A, Saito S.
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 45 Issue: 10 Pages: 1997-2006

    • DOI

      10.1111/jog.14083

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neonatal Alloimmune Thrombocytopenia: A Report of Four Cases.2019

    • Author(s)
      Uenaka M, Morizane M, Tanimura K, Deguchi M, Ebina Y, Hashimoto M, Morioka I, Yamada H.
    • Journal Title

      Kobe J Med Sci

      Volume: 64 Pages: 197-199

    • NAID

      120006599146

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 差分解説 不育症・習慣流産2019

    • Author(s)
      山田 秀人
    • Journal Title

      日本医事新報

      Volume: 4942 Pages: 4942-4942

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【妊娠高血圧症候群-PIHからHDPへ】抗リン脂質抗体と妊娠高血圧症候群2019

    • Author(s)
      出口 雅士、谷村 憲司、山田 秀人
    • Journal Title

      産科と婦人科

      Volume: 86 Pages: 223-229

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of high-dose i.v. immunoglobulin therapy for pregnant women with aspirin-heparin-resistant secondary antiphospholipid syndrome2018

    • Author(s)
      Maesawa Yoko、Deguchi Masashi、Tanimura Kenji、Morizane Mayumi、Ebina Yasuhiko、Yamada Hideto
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 17 Issue: 2 Pages: 149-154

    • DOI

      10.1002/rmb2.12080

    • NAID

      120006716620

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Factors associated with adverse pregnancy outcomes in women with systematic lupus erythematosus2018

    • Author(s)
      Deguchi Masashi、Maesawa Yoko、Kubota Shino、Morizane Mayumi、Tanimura Kenji、Ebina Yasuhiko、Yamada Hideto
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 125 Pages: 39-44

    • DOI

      10.1016/j.jri.2017.11.005

    • NAID

      120006604675

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel scoring system for predicting adherent placenta in women with placenta previa2018

    • Author(s)
      Tanimura K, Morizane M, Deguchi M, Ebina Y, Tanaka U, Ueno Y, Kitajima K, Maeda T, Sugimura K,
    • Journal Title

      Placenta

      Volume: 64 Pages: 27-33

    • NAID

      120006551692

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection2018

    • Author(s)
      Yamada H, Tanimura K, Tairaku S, Morioka I, Deguchi M, Morizane M, Nagamata S, Ozaki K, Ebina Y, Minematsu T
    • Journal Title

      J Infect Chemother

      Volume: 24 Issue: 9 Pages: 702-706

    • DOI

      10.1016/j.jiac.2018.04.010

    • NAID

      120006888539

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 抗リン脂質抗体陽性妊婦の管理2018

    • Author(s)
      山田 秀人
    • Journal Title

      日本医事新報

      Volume: 4911 Pages: 58-58

    • Related Report
      2018 Research-status Report
  • [Journal Article] Decidual CD68+HLA-DR+CD163? M1 macrophages increase in miscarriages with normal fetal chromosome2017

    • Author(s)
      Shimada Shigeki、Ebina Yasuhiko、Iijima Norifumi、Deguchi Masashi、Yamada Hideto
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: 79 Issue: 2 Pages: 1-5

    • DOI

      10.1111/aji.12791

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Natural killer cell activity in women with recurrent miscarriage: Etiology and pregnancy outcome2017

    • Author(s)
      Ebina Y, Nishino Y, Deguchi M, Maesawa Y, Nakajima Y, Yamada H
    • Journal Title

      J Reprod Immunol

      Volume: 120 Pages: 42-47

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Factors associated with adverse pregnancy outcomes in women with antiphospholipid syndrome: A multicenter study2017

    • Author(s)
      Deguchi M, Yamada H, Sugiura-Ogasawara M, Morikawa M, Fujita D, Miki A, Makino S, Murashima A
    • Journal Title

      J Reprod Immunol

      Volume: 122 Pages: 21-27

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Low levels of plasma protein S as a risk of adverse pregnancy outcome.2020

    • Author(s)
      Azumi M, Deguchi M, Shimizu M, Sasagawa Y, Morizane M, Tanimura K, Yamada H.
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Autoantibody against β2-glycoprotein I/HLA class II complexes as a new marker for antiphospholipid syndrome. Tanimura K, Sasagawa Y, Imafuku H, Morizane M, Deguchi M, Arase H, Yamada H.2020

    • Author(s)
      Tanimura K, Sasagawa Y, Imafuku H, Morizane M, Deguchi M, Arase H, Yamada H.
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pregnancies in women with recurrent pregnancy loss and protein S deficiency.2020

    • Author(s)
      Shimizu M, Deguchi M, Tanimura K, Morizane M, Yamada H.
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自己免疫疾患としての不育症.2020

    • Author(s)
      谷村憲司, 山田秀人.
    • Organizer
      第38回日本受精着床学会総会・学術講演会 (シンポジウム). 2021/10/1-23. 国内, WEB.
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] プロテインS 低下と不育症.2020

    • Author(s)
      出口雅士, 山田秀人.
    • Organizer
      第65回日本生殖医学会(ワークショップ). 2020/12/3-4. 国内, WEB.
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 不育症の話題、凝固異常とネオセルフ抗体.2020

    • Author(s)
      山田秀人.
    • Organizer
      女性医療WEBセミナー(指定講演). 2021/2/24. 国内, WEB.
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] β2GPI/HLA-DR複合体は産科的抗リン脂質抗体症候群の自己抗体の標的である.2020

    • Author(s)
      山田秀人, 出口雅士, 谷村憲司.
    • Organizer
      第65回日本生殖医学会. 2020/12/3-4. 国内, WEB.
    • Related Report
      2020 Annual Research Report
  • [Presentation] Autoantibody against beta2-glycoprotein I/HLA class II complex as a risk factor for recurrent pregnancy loss.2019

    • Author(s)
      Tanimura K, Saito S, Nakatsuka M, Nagamatsu T, Fujii T, Sasagawa Y, Deguchi M, Arase H, Yamada H
    • Organizer
      16th International Congress on Antiphospholipid Antibodies
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immunoglobulin therapy for congenital CMV infection and recurrent pregnancy loss.2019

    • Author(s)
      Yamada H
    • Organizer
      14th World Congress of the International Society for Immunology of Reproduction
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Congenital cytomegalovirus infection: advances in diagnosis, prevention and treatment.2019

    • Author(s)
      Yamada H
    • Organizer
      14th World Congress of the International Society for Immunology of Reproduction
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 不育症の基本と最近の話題2019

    • Author(s)
      山田 秀人
    • Organizer
      第62回兵庫県医師会学術セミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] TORCH症候群2019

    • Author(s)
      山田 秀人
    • Organizer
      第9回生長会産婦人科レビュー・コース
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 不育症:凝固異常と免疫異常2019

    • Author(s)
      山田 秀人
    • Organizer
      第64回日本生殖医学会学術講演会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 不育症の基本と最近の話題2019

    • Author(s)
      山田秀人
    • Organizer
      第62回兵庫県医師会学術セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] TORCH症候群2019

    • Author(s)
      山田秀人
    • Organizer
      第9回生長会産婦人科レビュー・コース(指定講演)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 母子感染~胎児期から新生児期まで2019

    • Author(s)
      山田秀人
    • Organizer
      第61回岐阜県周産期談話会(特別講演)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 先天性感染症の最前線~サイトメガロウイルスほか2019

    • Author(s)
      山田秀人
    • Organizer
      第71回日本産科婦人科学会学術集会(ランチョンセミナー)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] サイトメガロウイルス母子感染2018

    • Author(s)
      山田秀人
    • Organizer
      第70回日本産科婦人科学会学術講演会(教育講演)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 母子感染の最前線2018

    • Author(s)
      山田秀人
    • Organizer
      第18回埼玉県産婦人科医会手術・感染症研究会(特別講演)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 母子感染の最前線2018

    • Author(s)
      山田秀人
    • Organizer
      第45回日本産婦人科医会学術集会(教育講演)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 母子感染のリスクと対応2018

    • Author(s)
      山田秀人
    • Organizer
      鳥取県助産師会教育研修会(教育講演)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 先天性サイトメガロウイルス感染発生に関連する臨床・検査所見.母子感染に対する母子保健体制構築と医療開発技術のための研究(AMED 成育疾患克服等総合研究事業)2018

    • Author(s)
      山田秀人,内田明子,出口雅士,谷村憲司
    • Organizer
      平成30年度第2回班会議
    • Related Report
      2018 Research-status Report
  • [Book] 標準産科婦人科学第5版.綾部琢哉, 板倉敦夫編.2021

    • Author(s)
      山田秀人.自己免疫疾患.
    • Publisher
      医学書院, 東京
    • Related Report
      2020 Annual Research Report
  • [Book] ネオ・セルフ抗体.不育症.竹下俊行, 藤井知行, 山田秀人編.2020

    • Author(s)
      谷村憲司,山田秀人.
    • Publisher
      メジカルビュー社, 東京
    • Related Report
      2020 Annual Research Report
  • [Book] 産科的抗リン脂質抗体症候群の診断,治療.竹下俊行, 藤井知行, 山田秀人編2020

    • Author(s)
      山田秀人,出口雅士.
    • Publisher
      メジカルビュー社, 東京
    • Related Report
      2020 Annual Research Report
  • [Book] 不育症の基本と最近の話題2019

    • Author(s)
      山田 秀人
    • Total Pages
      5
    • Publisher
      兵庫県医師会
    • Related Report
      2019 Research-status Report
  • [Book] 不育症 2.診断と治療 9.免疫グロブリン大量療法2019

    • Author(s)
      出口 雅士、山田 秀人
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2019 Research-status Report
  • [Book] 不育症 2.診断と治療 10.不育症と抗リン脂質抗体2019

    • Author(s)
      谷村 憲司、出口 雅士、山田 秀人
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2019 Research-status Report
  • [Book] 今日の治療指針2018年版2018

    • Author(s)
      山田 秀人
    • Publisher
      医学書院
    • Related Report
      2018 Research-status Report
  • [Book] 実践臨床生殖免疫学2018

    • Author(s)
      出口 雅士、山田 秀人
    • Publisher
      中外医学社
    • Related Report
      2018 Research-status Report
  • [Book] 実践臨床生殖免疫学2018

    • Author(s)
      山田 秀人、出口 雅士
    • Publisher
      中外医学社
    • Related Report
      2018 Research-status Report
  • [Book] 読める生かせる説明できる!産科の臨床検査ディクショナリー2018

    • Author(s)
      出口 雅士、蝦名 康彦、山田 秀人
    • Publisher
      メディカ出版
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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