A secreted form of the asialoglycoprotein receptor, sH2a, as a novel potential noninvasive marker for liver fibrosis

• Published in: PloS one Vol. 6; no. 11; p. e27210
• Main Authors: Veselkin, Elena, Kondratyev, Maria, Lurie, Yoav, Ron, Efrat, Santo, Moshe, Reif, Shimon, Elashvili, Irma, Bar, Lana, Lederkremer, Gerardo Z
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.11.2011; Public Library of Science (PLoS)
• Subjects: Accuracy; Adult; Alanine; Alanine transaminase; Alanine Transaminase - blood; Alanine Transaminase - metabolism; Algorithms; Alternative splicing; Asialoglycoprotein Receptor - blood; Asialoglycoprotein Receptor - metabolism; Aspartate Aminotransferases - blood; Aspartate Aminotransferases - metabolism; Bilirubin - blood; Bilirubin - metabolism; Biology; Biomarkers; Biomarkers - blood; Cell surface; Coding; Confidence Intervals; Enzyme-linked immunosorbent assay; Female; Fibrosis; Gastroenterology; Hepatitis; Hepatitis C; Hepatitis C - blood; Hepatitis C - metabolism; Hepatocytes; Hepatology; Histology; Humans; Immunology; In Vitro Techniques; Laboratories; Life sciences; Liver; Liver cirrhosis; Liver Cirrhosis - blood; Liver Cirrhosis - metabolism; Liver diseases; Male; Measurement methods; Medicine; Middle Aged; Monoclonal antibodies; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Shedding; Variance analysis; Young Adult; Tel Aviv Israel; Israel
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027210

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. 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. 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. sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.