RESUMEN
BACKGROUND AND AIM: The human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function. METHODS: We measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals. RESULTS: sH2a levels varied minimally for the healthy individuals (150±21 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86. CONCLUSIONS: sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.
Asunto(s)
Receptor de Asialoglicoproteína/sangre , Receptor de Asialoglicoproteína/metabolismo , Cirrosis Hepática/metabolismo , Adulto , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Bilirrubina/sangre , Bilirrubina/metabolismo , Biomarcadores/sangre , Intervalos de Confianza , Femenino , Hepatitis C/sangre , Hepatitis C/metabolismo , Humanos , Técnicas In Vitro , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
AIM: To investigate the existence and levels of sH2a, a soluble secreted form of the asialoglycoprotein receptor in human serum. METHODS: Production of recombinant sH2a and development of a monoclonal antibody and an enzyme-linked immunosorbent assay (ELISA). This assay was used to determine the presence and concentration of sH2a in human sera of individuals of both sexes and a wide range of ages. RESULTS: The recombinant protein was produced successfully and a specific ELISA assay was developed. The levels of sH2a in sera from 62 healthy individuals varied minimally (147 ± 19 ng/mL). In contrast, 5 hepatitis C patients with cirrhosis showed much decreased sH2a levels (50 ± 9 ng/mL). CONCLUSION: Constant sH2a levels suggest constitutive secretion from hepatocytes in healthy individuals. This constant level and the decrease with cirrhosis suggest a diagnostic potential.