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Submitted on November 16, 2001
Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109-0666
Corresponding Author: berettal{at}umich.edu
Chronic infections with hepatitis B (HBV) and hepatitis C (HCV) viruses are major risk factors for hepatocellular carcinoma (HCC). We have utilized a proteomic approach to determine whether a distinct repertoire of autoantibodies can be identified in HCC. Sera from 37 patients with HCC and 31 subjects chronically infected with HBV or HCV without HCC were investigated. Sera from 116 patients with other cancers, 3 patients with systemic lupus erythematosus and 24 healthy subjects were utilized as controls. We report the identification of 8 proteins, for each of which, autoantibodies were detected in sera from more than 10% of patients with HCC but not in sera from healthy individuals (p<0.05). Autoantibodies to four of these proteins were detected at a comparable frequency in sera from patients with chronic hepatitis. The other four proteins, which consisted of calreticulin isoforms, cytokeratin 8, nucleoside diphosphate kinase A and F1-ATP synthase beta subunit, induced autoantibodies among patients with HCC, independently of their HBV/HCV status. Calreticulin, and a novel truncated form of calreticulin (Crt32) we have identified, most commonly elicited autoantibodies among patients with HCC (27%). We conclude that a distinct repertoire of autoantibodies is associated with HCC that may have utility in early diagnosis of HCC among high-risk subjects with chronic hepatitis.
Revised on January 18, 2002
Accepted on January 24, 2002
A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis
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