Novel murine model of recurrent miscarriages

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09885
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Hokkaido University
• Principal Investigator: Oku Kenji 北海道大学, 大学病院, 講師 (70544295)
• Research Collaborator: Ohmura Kazumasa
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 不育症 / 補体活性化 / C1q / 胎盤不全 / 抗リン脂質抗体症候群

Outline of Final Research Achievements

We demonstrated that the complement activation detected in the sera of recurrent miscarriages patents is not only related to antiphospholipid syndrome (APS) but generally observed in the recurrent miscarriage patients with or without APS. A pathogenic antibody that targets an uncoverd-epitope one the anionicphospholipid-bound triggers the overwhelming activation of the complement system. The aC1q with the complement activation were prevalently observed in the sera of the recurrent miscarriage patients without known etiology as well as the APS patients. In the murine model, which the BALB/c pregnant mouse administered with the monoclonal aC1q, showed the upregulation of the serum C3a level with the increased complement protein depositions in the placenta with the high prevalence of embryonic absorption and the placenta/placental weight loss.These were improved to the same degree as the control group by the pre-administration of the anti-C5a receptor antibody.

Free Research Field

自己免疫疾患の臨床・基礎研究

Academic Significance and Societal Importance of the Research Achievements

抗Cq抗体は、不育症や習慣流産における新たな病原性自己抗体である可能性が示唆された。その存在は補体系の活性化を介して胎盤不全を惹起し流産に至ると考えられる。そのため、不育症や流産においてaC1qは新たな治療ターゲットや病態マーカーになる可能性がある。少子化が進む我が国において不育症や習慣流産は大きな問題であり、本研究によってリスク例の抽出や新たな病態理解による新規治療が行われる可能性がある。