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.
Bibliographical noteFunding Information:
The authors would like to thank CONACYT for the Ph.D. student grant (no. 388476/256990) and 367B01002 Program of Tecnológico de Monterrey as well as MAS Juan Miguel Tenorio Pedraza, MAS, for his help with the statistical analysis and Veterinary Felipe Guadalupe Guerrero Gonzalez for his help with the animal model.
Copyright © 2016 Florent Duval et al.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Biochemistry
- Biochemistry, medical