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Frequency of diagnostically significant hepatitis B surface antigen mutants
Author(s) -
Kuhns Mary C.,
McNamara Anne L.,
Holzmayer Vera,
Lou Sheng C.,
Busch Michael P.
Publication year - 2007
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20962
Subject(s) - hbsag , virology , epitope , hepatitis b virus , immunoassay , hepatitis b , biology , antibody , antigen , mutation , medicine , virus , gene , immunology , genetics
Mutations in the hepatitis B surface antigen (HBsAg) gene can result in amino acid changes in the HBsAg immunodominant “a” determinant that affect the binding of antibodies used in immunoassays. The effects of mutations on immunoassay detection of HBsAg can range from little or no change in reactivity, to significantly reduced reactivity, to complete loss of detection. The frequency of mutations affecting HBsAg detection among hepatitis B virus (HBV) infected individuals in the United States is largely unknown. We investigated the frequency and nature of diagnostically significant HBsAg variants in the United States by evaluating 186 chronically infected, HBsAg positive individuals. As a first level differential screening strategy to serologically identify variants with potential diagnostic importance, HBsAg levels were estimated using two different immunoassays that employ antibodies recognizing different epitopes and that are known to differ in their detection of frequently reported mutations. Six individuals (3.2%) had results that were qualitatively or quantitatively discordant by at least ten‐fold between the two immunoassays. All of the discordant samples were HBV DNA positive. Results of epitope mapping showed that one sample had no detectable wild‐type HBsAg but contained an altered HBsAg consistent with a mutation in the second loop of the “a” determinant. Another specimen was shown to have a mutation in the HBsAg gene resulting in an asparagine substitution at amino acid 134 within the first loop of the “a” determinant. Results of this study indicate that at least 1.1% of HBsAg positive individuals may carry HBV mutations that affect detection by HBsAg immunoassays. J. Med. Virol. 79:S42–S46, 2007. © 2007 Wiley‐Liss, Inc.