Failed adoptive immunity transfer: reactivation or reinfection?
A 26-year-old female bone marrow transplant (BMT) recipient was hepatitis B surface antigen (HBsAg) and hepatitis B e antibody (HBeAb) positive. The donor, her human leucocyte antigen (HLA)-compatible sister, was HBsAg negative but hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) positive. Twelve weeks post-BMT the patient became HBsAg negative, as determined using a monoclonal antibody-based assay. At 16 weeks post-BMT, HBsAg became undetectable by monoclonal and polyclonal immunoassay with seroconversion to HBsAb; however, at 24 weeks post-BMT the patient again became HBsAg positive. Both the recipient and the donor were retrospectively tested by hepatitis B virus (HBV) polymerase chain reaction (PCR) and found to be positive. The recipient displayed variants at amino acids 4 and 47 of the surface (S) gene prior to BMT. These mutations were not detected 32 weeks post-BMT when the S gene sequence was identical to that of an adr prototype. The donor was found to have four unique amino acid substitutions at positions 30, 98, 101 and 210 of the S gene. However, in vitro-expressed HBsAg from the donor was detected by commercial kits and an immunofluorescence assay, indicating that antigenic alteration did not explain HBsAg negativity. This donor highlights the value of PCR as the gold standard test for current HBV infection. It also demonstrates that discordance between two commercial HBsAg assays may not always be caused by antigenic variants. The second episode of hepatitis may theoretically have been caused by reactivation, selection of an escape mutant by HBsAb, reinfection or recombination. We suggest it was reactivation because none of the donor variants was seen in the recipient post-BMT.
Ireland
J
J
Institute of Virology, University of Glasgow, UK.
Hino
K
K
Lau
G K
GK
Cheng
C C
CC
Carman
W F
WF
D019264:Adoptive Transfer; D000328:Adult; D000595:Amino Acid Sequence; D016026:Bone Marrow Transplantation; D005260:Female; D005455:Fluorescent Antibody Technique; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012008:Recurrence; D017422:Sequence Analysis, DNA; D014775:Virus Activation
D006514:Hepatitis B Surface Antigens