Detection of a hepatitis B surface antigen variant emerging in a patient with chronic lymphocytic leukaemia treated with fludarabine
Autor: | Helen Pandelidaki, Alexandra Alexopoulou, Spyros P. Dourakis, Athanasios J. Archimandritis, Peter Karayiannis |
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Rok vydání: | 2006 |
Předmět: |
HBsAg
Antigenicity Antineoplastic Agents Biology medicine.disease_cause Virology medicine Humans Amino Acid Sequence Peptide sequence Phylogeny Vidarabine Aged Hepatitis B virus Hepatitis B Surface Antigens virus diseases Hepatitis B medicine.disease Leukemia Lymphocytic Chronic B-Cell digestive system diseases Fludarabine Infectious Diseases HBeAg Mutation Female medicine.drug |
Zdroj: | Journal of Medical Virology. 78:1043-1046 |
ISSN: | 1096-9071 0146-6615 |
Popis: | Fludarabine is used widely for the treatment of chronic lymphocytic leukaemia, but not as yet implicated in the emergence of hepatitis B surface antigen (HBsAg) variants following hepatitis B virus (HBV) reactivation. Such a variant was detected in a 78-year-old female who was HBsAg(-)/anti-HBc(+)/anti-HBs(+)/anti-HBe(+), and with normal ALT levels, who developed HBV reactivation after fludarabine treatment. She had high HBV-DNA levels, and became positive for HBeAg, in the absence of detectable HBsAg. HBV-DNA was extracted from serum and the HBsAg encoding region of the genome was amplified by PCR, followed by cloning and sequencing. The HBV strain appeared to be subtype adw, but had higher nucleotide homology with ayw than adw isolates, supported further by phylogenetic tree analysis. Amino-acid sequence comparisons over the alpha determinant region revealed the following substitutions: C124N, G130R, and N146S. There were also unique substitutions outside the alpha determinant. All these mutations appeared to have a profound effect on the antigenicity of this region, which resulted in failure to detect HBsAg by commercially available diagnostic assays. It is concluded that a surface variant emerged in an HBsAg(-)/anti-HBs(+) patient with chronic lymphocytic leukaemia following fludarabine treatment, with an unprecedented number of amino-acid substitutions in the alpha determinant region of HBsAg, including a subtype switch. |
Databáze: | OpenAIRE |
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