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.