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Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis

Author

Listed:
  • Tomoyuki Mutoh

    (Tohoku University Graduate School of Medicine)

  • Tsuyoshi Shirai

    (Tohoku University Graduate School of Medicine)

  • Tomonori Ishii

    (Tohoku University Graduate School of Medicine)

  • Yuko Shirota

    (Tohoku University Graduate School of Medicine)

  • Fumiyoshi Fujishima

    (Tohoku University Graduate School of Medicine)

  • Fumiaki Takahashi

    (Iwate Medical University)

  • Yoichi Kakuta

    (Tohoku University Graduate School of Medicine)

  • Yoshitake Kanazawa

    (Tohoku University Graduate School of Medicine)

  • Atsushi Masamune

    (Tohoku University Graduate School of Medicine)

  • Yoshikatsu Saiki

    (Tohoku University Graduate School of Medicine)

  • Hideo Harigae

    (Tohoku University Graduate School of Medicine)

  • Hiroshi Fujii

    (Tohoku University Graduate School of Medicine)

Abstract

The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis. Here, we identify cell-surface autoantigens using an expression cloning system. A cDNA library of endothelial cells is retrovirally transfected into a rat myeloma cell line from which AECA-positive clones are sorted with flow cytometry. Four distinct AECA-positive clones are isolated, and endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) are identified as endothelial autoantigens. Autoantibodies against EPCR and SR-BI are detected in 34.6% and 36.5% of cases, respectively, with minimal overlap (3.8%). Autoantibodies against EPCR are also detected in ulcerative colitis, the frequent comorbidity of TAK. In mechanistic studies, EPCR and SR-BI function as negative regulators of endothelial activation. EPCR has also an effect on human T cells and impair Th17 differentiation. Autoantibodies against EPCR and SR-BI block the functions of their targets, thereby promoting pro-inflammatory phenotype.

Suggested Citation

  • Tomoyuki Mutoh & Tsuyoshi Shirai & Tomonori Ishii & Yuko Shirota & Fumiyoshi Fujishima & Fumiaki Takahashi & Yoichi Kakuta & Yoshitake Kanazawa & Atsushi Masamune & Yoshikatsu Saiki & Hideo Harigae & , 2020. "Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15088-0
    DOI: 10.1038/s41467-020-15088-0
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