Detection of Autoantibodies to Vascular Endothelial Growth Factor Receptor-3 in Bile Duct Ligated Rats and Correlations with a Panel of Traditional Markers of Liver Diseases

Abstract

There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) has TAA potential since it is involved in cholangiocytes and lymphatic vessels proliferations during CCLDs. This study aims to detect autoantibodies directed at VEGFR-3 during bile duct ligation- (BDL-) induced cholestatic injury in rat sera and investigate whether they could be associated with traditional markers of liver damage, cholestasis, and fibrosis. An ELISA was performed to detect anti-VEGFR-3 autoantibodies in sera of rats with different degree of liver injury and results were correlated with aminotransferases, total bilirubin, and the relative fibrotic area. Mean absorbances of anti-VEGFR-3 autoantibodies were significantly increased from week one to week five after BDL. The highest correlation was observed with total bilirubin (R 2 = 0.8450, P = 3.04e − 12). In conclusion, anti-VEGFR-3 autoantibodies are early produced during BDL-induced cholestatic injury, and they are closely related to cholestasis, suggesting the potential of anti-VEGFR-3 autoantibodies as NIBMs of cholestasis in CCLDs and justifying the need for further investigations in patients with CCLD.

Elongated Flexuous Plant Virus-Derived Nanoparticles Functionalized for Autoantibody Detection

“…Multimeric peptide presentation on the surface of TuMV VNPs increases its detectability by specific antibodies in conventional immunoassays like ELISA [15,17,46]. To evaluate this in the Hsp60-VLPs construct, ELISA and dot-blot assays were performed using three types of presentations: Hsp60-VLPs, free Hsp60 peptide, and complete Hsp60 protein, as shown in Figure 2.…”

“…To address these challenges, the use of nanoparticles as a multimeric presentation system is an alternative approach, which should provide high sensitivity and solve the epitope–adhesion problem [6,9,51,52]. We have previously shown that functionalized nanoparticles derived from TuMV significantly increased antibody detection with respect to conventional systems [16,17,46]. Although this system has not been used in the diagnosis, progression, and/or prognosis of specific pathologies yet, its potential makes it a good candidate for the design of a hypersensitive analysis system by the detection of serum autoantibodies.…”

Biotechnological engineering of Turnip mosaic virus-derived nanoparticles by functionalization with natural compounds of different biological activities

“…The fact that the N-terminus domain is exposed to the environment makes peptide-fusion possible. In previous studies, the addition of a peptide in this domain does not affect viral infectivity (Ibort, 2012;Duval et al, 2016). Maintaining infectivity (in virions) and self-assembly capacity after the genetic fusion of a peptide is key for assessing feasibility of genetic functionalization.…”