The prothrombin/MHC II complexes on cell-surface of monocytes is the antigenic targets in antiphospoholipid syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08876
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Hokkaido University
• Principal Investigator: Fujieda Yuichiro 北海道大学, 大学病院, 助教 (70790872)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 抗リン脂質抗体 / 単球 / ミスフォールドタンパク

Outline of Final Research Achievements

1) PMA treated THP-1 cells synthesized PT, which showed stronger binding with aPS/PT compared with non-pathogenic monoclonal anti-PT antibody. ２) aPS/PT binding to PT/MHC II complexes was confirmed in co-stimulated THP-1 cells and cell-surface PT was detected on monocyte in APS patient and aPS/PT binding to the monocyte was confirmed. 3) Cell-surface PT was detected on monocytes in two out of 18 APS patients and aPS/PT binding to the monocytes was confirmed. 4) Immunofluorescence staining, and PLA identified PT/HLA complex expressed on monocyte surface in patients with APS.
5) TF mRNA and protein expression was significantly higher in monocyte cocultured with APS IgG compared with healthy control IgG. 6) When the tests were performed with and without warfarin in a same patient, aPS/PT binding was disappeared without warfarin, indicating that Warfarin may affect the prothrombin expression in patients with APS.

Free Research Field

抗リン脂質抗体症候群

Academic Significance and Societal Importance of the Research Achievements

抗リン脂質抗体症候群（APS）は凝固・線溶タンパクに対する自己抗体により、血栓症または妊娠合併症を生じる疾患である。抗リン脂質抗体（aPL）の抗原はリン脂質ではなく、リン脂質に結合する凝固・線溶タンパクである。新たに提唱されたミスフォールド/HLA複合体に対する抗体の検出は抗リン脂質抗体の新たな検出方法であること、さらにプロトロンビン/HLA複合体が単球で発現している現象は、APSの病態生理の解明に近づいた発見である。さらにワーファリンのみが治療薬としてなぜ有効なのかを間接的に証明できる可能性がある。