Reactivity to B cell epitopes within hepatitis C virus core protein and hepatocellular carcinoma.
Our aim was to investigate the existence of an association between B cell responsiveness to hepatitis C virus (HCV) core protein and progression of liver disease. In fact, the persistence of HCV infection is permitted by avoidance of viral clearance, despite chronic inflammation in the liver; this process ends with the development of hepatocellular carcinoma in many patients. On the basis of computerized prediction of antigenicity of the genomic sequence of HCV core protein, three 15-mer peptides (named Q15V, R15P, and G15V) were synthesized to be used as antigens in an enzyme immunoassay. Sera from 97 patients (65 males and 32 females) were tested: 43 patients had mild chronic liver disease (steatofibrosis, chronic persistent, or chronic active hepatitis) and 54 had cirrhosis, which was complicated by hepatocellular carcinoma (HCC) in 19. Seventy-six patients were positive to anti-HCV testing by second generation ELISA and 21 were negative. Rates of positivity for synthetic peptides in anti-HCV-positive versus anti-HCV negative patients were as follows: 53 of 76 and 0 of 21 for anti-Q15V; 41 of 76 and 0 of 21 for R15P; and 67 of 76 and 2 of 21 for G15V. Rates of positivity to anti-Q15V and anti-G15V were similar among diagnostic groups (Pearson's chi 2, 1.97, P > 0.10 and 0.45, P > 0.10), whereas anti-R15P antibodies were detected at a significantly lower rate in patients with HCC (2/13) in comparison to mild chronic liver disease (22/35) and cirrhosis (17/28) (Pearson's chi 2, 9.42, P < 0.01). We conclude that anti-R15P antibodies are uncommon in anti-HCV-positive patients with HCC. During the course of chronic HCV infection, anti-R15P testing might help to identify a subgroup at higher risk to develop HCC.
Pirisi
M
M
Department of Experimental and Clinical Pathology and Medicine, University of Udine, Italy.
Fabris
C
C
Toniutto
P
P
Vitulli
D
D
Soardo
G
G
Falleti
E
E
Gonano
F
F
Ferroni
P
P
Gasparini
V
V
Bartoli
E
E
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000150:complications*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006508:Hepatitis Antibodies / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014758:Viral Core Proteins / Q000276:immunology*
D000939:Epitopes; D006508:Hepatitis Antibodies; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus