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.
Highlights
The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis
G human umbilical vein endothelial cells (HUVECs) cDNA fragments inserted into the genomic DNA of C6 clones established with W10-59 IgG and C7 by using G10-43 IgG were amplified, and PCR products were electrophoresed on a 0.8% agarose gel. h DNA sequencing was performed for the PCR products obtained around 3000 bp for C7, followed by BLAST analysis. i C6 and C7 were stained with anti-human SR-BI antibody or isotype control, followed by incubation with secondary antibody and flow cytometry analysis. j The expression vector SR-BI-IRES-GFP was transfected into YB 2/0 cells, and the cells were stained with
0.5 mg/mL control IgG, W10-59 IgG, or G10-43 IgG, followed by incubation with secondary antibody and flow cytometry analysis. k Inhibition tests for binding activities to YB2/0 cells overexpressing SR-BI were conducted using 0.5 mg/mL W10-59 IgG with soluble recombinant SR-BI at the indicated concentrations. l YB2/0 cells expressing with or without SR-BI were reacted with control, W10-59, or G10-43 serum
Summary
The presence of antiendothelial cell antibodies (AECAs) has been documented in Takayasu arteritis (TAK), a chronic granulomatous vasculitis. 4 Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. Granulomatous vasculitis is a typical pathological finding, and T cells have been implicated as key players; myeloid cells, including macrophages, are effector cells that promote disease progression[4,5] In addition to such cellular immune reactions, the involvement of B cells and autoantibodies has been described[6]. Since the 1990s, high numbers of patients with TAK who had antiendothelial cell antibodies (AECAs) have been reported[9,10,11]; several studies identified the pathogenic effects of AECAs in TAK, including endothelial cell activation[12], cytotoxicity[13], cytokine production, and apoptosis[14]. Autoantigens may be either constitutively expressed and translocated from intracellular compartment to membrane
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
