Discussion
In this study, we observed a significant increase in recipient HBsAb
titers within the first 3 months after the transplant even in patients
who were seronegative before the transplant, which can be explained as
follows: (1) There may have been a transfer of antibody-producing cells
from the donor. After myeloablation, the vast majority of specific
helper T cells and B cells are transferred through allografts
[9-12]. (2) There may have been persistent antigens and plasma cells
in the recipients. The fact that administration of a recall protein
antigen to recipients during conditioning can increase the
posttransplant antibody levels shows the role of the antigen in
recipients because it is not possible for recipient B cells to
differentiate into plasma cells and produce antigen-specific antibodies
at this time. In contrast, the antigens in recipients may stimulate
donor B cells to differentiate into plasma cells [12].
Although HBsAb titers in recipients can remain positive or even show an
upward trend in the early stage after transplantation, children who
undergo PBSCT are inevitably at high risk of losing previously acquired
immunity to HBV as a result of initially impaired humoral immunity
because of the limited antibody repertoire and prolonged inadequate T
cell-dependent B cell response [4]. Published studies with different
numbers of patients and follow-up periods have reported the incidence of
HBsAb disappearance, which varies from 49.6%-100% [13-16].
Consistent with a previous study, we observed a decrease in HBsAb titers
6 months after the transplant, with 10 patients having unmeasurable
HBsAb levels, and 63.2% of the patients in this study finally lost
protective immunity to HBV within one year after transplantation.
It is theoretically feasible to transfer both cellular and humoral
immunity from vaccinated donors to recipients through HSCT
[12,17-21]. However, clinical
studies assessing the impact of donor immunity status on
the posttransplant HBsAb levels of recipients have produced inconclusive
results [12,14,16,22-24]. One study conducted by Storek et al.
[23] did not show substantial differences in posttransplant HBsAb
titers between recipients who had vaccinated donors and those who had
unvaccinated donors, and Kaloyannidis et al. [14] reported the same
findings. Another study with a small sample size reported a benefit to
the recipients of vaccinating donors with the hepatitis B vaccine
[12], which was broadly in line with the finding from a study by
Park et al. [16], which demonstrated that there was a protective
effect of donor HBsAb on the maintenance of recipient HBsAb positivity.
In our study, there was a significant correlation between recipient
HBsAb titers before and after PBSCT, and initial HBsAb titers higher
than 207.5 IU/L had a protective effect on the maintenance of
posttransplant antibody levels. In contrast, the presence of donor
immunity did not substantially influence the recipient HBsAb levels or
the final HBsAb negative conversion rate after PBSCT. Hence, the
evidence supporting the vaccination of donors to improve recipient
antibody titers is weak.
ATG was widely administered in patients in this study during the
conditioning regimen to decrease the occurrence of GVHD, and a
considerable proportion of the patients received corticosteroids, which
are associated with delayed immune recovery, due to severe GVHD [4].
As expected, these were significant factors that influenced the HBsAb
titers according to the univariate
analysis. In accordance with reported studies [14,16], the presence
of GVHD was also a significant risk factor for HBsAb disappearance
within one year after transplantation.
There were certain limitations of our study. The protocol was designed
based on a single organization with a relatively small population of
patients and used retrospective data. Furthermore, it is unlikely that
we obtained comprehensive HBV vaccination data from the donors due to
the nature of the research, so we could not analyze detailed information
about the type of donor immunity.
In summary, in most recipients,
pretransplant immunity to HBV is lost after PBSCT. A high pretransplant
HBsAb titer in the recipient had a protective effect against HBsAb
disappearance, but the presence of donor immunity did not significantly
influence the posttransplant HBsAb titer. Consequently, careful
monitoring of HBsAb status both before and after transplantation and
providing booster hepatitis B vaccination to recipients who became HBsAb
seronegative in a timely manner should be considered. In addition,
vaccinating recipients before
transplantation to achieve high HBsAb levels may be beneficial to the
maintenance of HBsAb positivity after transplantation.