title: 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.
authors.affiliation: Catedra de Terapia Celular, Escuela de Medicina, Tecnológico de Monterrey, Avenida Morones Prieto 3000 Pte., 64710 Monterrey, NL, Mexico.
authors.forename: Florent
authors.initials: F
authors.lastname: Duval
authors.affiliation: Catedra de Terapia Celular, Escuela de Medicina, Tecnológico de Monterrey, Avenida Morones Prieto 3000 Pte., 64710 Monterrey, NL, Mexico.
authors.forename: Delia Elva
authors.initials: DE
authors.lastname: Cruz-Vega
authors.affiliation: Centro de Biotecnología y Genómica de Plantas (CBGP), UPM-INIA, Campus de Montegancedo, Autovía M40, Km 38, Pozuelo de Alarcón, 28223 Madrid, Spain.
authors.forename: Ivonne
authors.initials: I
authors.lastname: González-Gamboa
authors.affiliation: Catedra de Terapia Celular, Escuela de Medicina, Tecnológico de Monterrey, Avenida Morones Prieto 3000 Pte., 64710 Monterrey, NL, Mexico.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: González-Garza
authors.affiliation: Centro de Biotecnología y Genómica de Plantas (CBGP), UPM-INIA, Campus de Montegancedo, Autovía M40, Km 38, Pozuelo de Alarcón, 28223 Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ponz
authors.affiliation: Centro de Biotecnología y Genómica de Plantas (CBGP), UPM-INIA, Campus de Montegancedo, Autovía M40, Km 38, Pozuelo de Alarcón, 28223 Madrid, Spain.
authors.forename: Flora
authors.initials: F
authors.lastname: Sánchez
authors.affiliation: Servicio de Anatomía Patológica y Citopatología, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Madero y Dr. Aguirre Pequeño, 64460 Monterrey, NL, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Alarcón-Galván
authors.affiliation: Catedra de Terapia Celular, Escuela de Medicina, Tecnológico de Monterrey, Avenida Morones Prieto 3000 Pte., 64710 Monterrey, NL, Mexico.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Moreno-Cuevas
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism*; D001663:Bilirubin / Q000378:metabolism*; D002779:Cholestasis / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008107:Liver Diseases / Q000276:immunology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3; D001663:Bilirubin