Comprehensive Regression Analysis of Hepatitis B Virus X Antigen Level and Anti-HBx Antibody Titer in the Sera of Patients with HBV Infection

József PÁL1, Zoltán NYÁRÁDY2, Ilona MARCZINOVITS4, Alajos PÁR3, Younes Saleh ALI5, György BERENCSI6, Krisztián KVELL1, Péter NÉMETH1

1Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Pécs, Hungary
2Department of Dentistry, Oral and Maxillofacial Surgery, University of Pécs, Pécs, Hungary
31st Department of Medicine, Faculty of Medicine, University of Pécs, Pécs, Hungary
4Department of Anatomy, University of Szeged, Szeged, Hungary
5Faculty of Medicine, University of Garyounis, Benghazi, Libyan Jamahiriya
6Division of Virology, Béla Johan National Center for Epidemiology, Pécs, Hungary
7Clinical Neuroscience Research Group of the Hungarian Academy of Sciences, University of Pécs, Pécs, Hungary


Although the pathogenetic significance of hepatitis B virus x protein (HBxAg) in chronic hepatitis, liver cirrhosis, and primary hepatocellular carcinoma has already been studied, the comparative analyses of both the actual serum HBxAg levels and antibody production against various HBx epitopes have been examined to lesser extent. We have simultaneously investigated the relationship between antibody production (IgG and IgM) against the HBxAg fragments and HBxAg level in the sera of patients with acute (14) or chronic hepatitis (80) and symptomless carriers (12). A recently developed sandwich-type ELISA was used for the quantitative measurements of HBxAg. Overlapping recombinant and synthetic antigens were used to map the fine epitope specificities of circulating anti-HBx antibodies. In acute hepatitis, we have found high and homogenous correlation in the IgM type immune responses against all the examined HBxAg regions. Moreover, strong correlation has been observed between IgG type immune responses to a characteristic C-terminal region (C1: 79-117) and the longest fragment (X: 10-143). Moderate correlation has been found between HBxAg concentration and the IgG type anti-HBx antibody levels against C-terminus of HBxAg in patients with chronic hepatitis. In the case of symptomless carriers, there were also demonstrable associations in the immune responses against the C-terminal sequences; however, significant correlations were found for antibody production against the N-terminal region as well. The examinations show that the C-terminal sequence, responsible for transactivation, promotes an efficient IgG antibody response in all three groups of patients, whereas the negative regulator N-terminal part of the HBxAg molecule for the most part does not trigger antibody production. This suggests that the immune responses against various - biologically active - epitopes of the HBxAg may have a different role in the pathogenesis of hepatitis and may be used as prognostic markers in human HBV infections. Pathology & Oncology Research, Vol 12, Nr 1, 34-40, 2006

Key words: Hepatitis B virus; HBxAg; immunoserology; epitope mapping; antibody response

Received: Oct 25, 2005; accepted: Feb 10, 2006
Correspondence: Péter NÉMETH, Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Szigeti u. 12. Pécs H-7643, Hungary; Tel: +36-72-536290, Fax: +36-72-536289; E-mail:

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