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 d onor, her human leucocyte antigen (HLA)-compatible sister, was HBsAg negati ve but hepatitis B surface antibody (HBsAb) and hepatitis B core antibody ( HBcAb) positive. Twelve weeks post-BMT the patient became HBsAg negative, a s determined using a monoclonal antibody-based assay. At 16 weeks post-BMT, HBsAg became undetectable by monoclonal and polyclonal immunoassay with se roconversion to HBsAb; however, at 24 weeks post-BMT the patient again beca me HBsAg positive, Both the recipient and the donor were retrospectively te sted by hepatitis B virus (HBV) polymerase chain reaction (PCR) and found t o 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 we eks post-BMT when the S gene sequence was identical to that of an adr proto type. The donor was found to have four unique amino acid substitutions at p ositions 30, 98, 101 and 210 of the S gene. However, in vitro-expressed HBs Ag from the donor was detected by commercial kits and an immunofluorescence assay, indicating that antigenic alteration did not explain HBsAg negativi ty. This donor highlights the value of PCR as the gold standard test for cu rrent HBV infection. It also demonstrates that discordance between two comm ercial HBsAg assays may not always be caused by antigenic variants, The sec ond 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.