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

Nature Communications
Tomoyuki MutohHiroshi Fujii

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.

Associated Datasets

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Citations

Jun 10, 2020·Inflammation and Regeneration·Hajime Yoshifuji, Chikashi Terao
Aug 28, 2020·Current Rheumatology Reports·Ryu WatanabeCornelia M Weyand
Oct 13, 2020·Current Rheumatology Reports·B HellmichR Luqmani
Feb 12, 2021·Current Rheumatology Reports·Enrico TombettiDario Camellino
Feb 26, 2021·Arthritis Research & Therapy·Rongyi ChenLindi Jiang
Mar 18, 2021·Scandinavian Journal of Rheumatology·T ShiraiH Harigae
Nov 8, 2020·Science Advances·Michelle M CastilloRashmi Sood
Apr 20, 2021·Atherosclerosis·Alison H Clifford, Jan Willem Cohen Tervaert
Jul 22, 2021·The International Journal of Cardiovascular Imaging·Shanshan JiaXiaoping Chen
Aug 15, 2021·Gastroenterology·Takeshi KuwadaHiroshi Seno
Mar 29, 2021·Gastroenterology·Tsuyoshi ShiraiHiroshi Fujii

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Methods Mentioned

BETA
electrophoresis
flow cytometry
PCR
immunoprecipitation
biopsy
ESR
enzyme-linked immunosorbent assay
density gradient centrifugation
Antibody
Fluorescence

Software Mentioned

GraphPad
GraphPad Prism
BLAST
FlowJo

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