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

Tomoyuki Mutoh, Tsuyoshi Shirai (), Tomonori Ishii, Yuko Shirota, Fumiyoshi Fujishima, Fumiaki Takahashi, Yoichi Kakuta, Yoshitake Kanazawa, Atsushi Masamune, Yoshikatsu Saiki, Hideo Harigae and Hiroshi Fujii
Additional contact information
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

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15088-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15088-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15088-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().