Anna Lucia Tornesello, Ulf Reimer, Pavlo Holenya, Tobias Knaute, Francesca Pezzuto, Francesco Izzo, Luigi Buonaguro, Angelo Salomone Megna, Franco Maria Buonaguro* and Maria Lina Tornesello* Pages 2736 - 2747 ( 12 )
Background: Chronic infection with hepatitis C virus (HCV) is among the major causes of hepatic fibrosis, cirrhosis, as well as hepatocellular carcinoma (HCC), and it is associated with a significant risk of developing lymphoproliferative disorders. The rate of clinical disease progression is variable depending on multiple host and viral factors, including immune response.
Methods: To perform a comprehensive epitope mapping of anti-HCV antibodies in patients suffering from HCV-related liver or lymphoproliferative diseases, we analyzed clinical samples on a peptide microarray platform made of 5952 overlapping 15-mer synthetic peptides derived from the whole HCV proteome. We evaluated the antibody profile of 71 HCV-positive patients diagnosed with HCC, mixed cryoglobulinemia (MC), and HCV chronic infection. Antibody reactivity against virus peptides was detected in all HCVpositive patients. Importantly, the signal amplitude varied significantly within and between diverse patient groups.
Results: Antibody reactivity against C peptides were found generally low in HCV chronically infected asymptomatic subjects and increasingly high in HCC and MC patients. Moreover, we found a statistically significant higher IgG response in HCC and MC patients against specific domains of HCV C, E2, NS3, NS4A, NS4B, NS5A, and p7 compared to HCV-positive subjects.
Conclusion: In conclusion, our data suggest that immune response against specific HCV protein domains may represent useful biomarkers of disease progression among HCVpositive patients and suggest that peptide microarrays are good tools for the screening of immunotherapy targets in preclinical HCV research.
Hepatocellular carcinoma (HCC), Mixed cryoglobulinemia (MC), Hepatitis C virus (HCV), peptides microarray, antibodies, peptide biomarker, lymphoproliferative disorders.
Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131 Napoli, JPT Peptide Technologies GmbH, Berlin, JPT Peptide Technologies GmbH, Berlin, JPT Peptide Technologies GmbH, Berlin, Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131 Napoli, Hepatobiliary Surgery Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131 Napoli, Innovative Immunological Models, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale, 80131 Napoli, Infectious Diseases Unit, Azienda Ospedaliera San Pio, Benevento, Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131 Napoli, Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131 Napoli