Hepatitis B surface antigen variant with multiple mutations in the a determinant in an agammaglobulinemic patient

Abstract

A patient with agammaglobulinemia developed acute hepatitis that progressed to chronic liver disease with high levels of hepatitis B virus (HBV) DNA in the absence of detectable HBsAg. Sequencing of the a determinant region of HBsAg revealed multiple amino acid substitutions that, unusually, also included a substitution at position 122 that defines subtype specificity. All of these mutations had a profound effect on the antigenicity of this region, which led to the complete failure of variant detection by commercially available routine diagnostic assays or laboratory-based monoclonal antibody assays.

FIG. 1.

Distribution of the amino acid substitutions detected in the variant. The amino acid sequences from codon positions 110 to 180 of the surface antigen gene were compared with three reference sequences, those of subtypes ayw (GenBank accession no. HPBAYW), adw (GenBank accession no. M54923), and adr (GenBank accession no. D00630). The percentages of the major and minor clones detected are also noted. Boldface letters represent the a-determinant region.

FIG. 2.

Phylogenetic tree analysis showing clustering of the complete HBV genome sequences obtained from GenBank (the accession numbers are indicated) by subtype. AY341335 is the isolate from the present study.