Department of Internal Medicine 5, Hematology/Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Glückstrasse 6, 91054, Erlangen, Germany.
Department of Biology, Division of Genetics, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Ann Hematol. 2020 Aug;99(8):1895-1906. doi: 10.1007/s00277-020-04072-9. Epub 2020 Jun 9.
After allogeneic hematopoietic stem cell transplantation (HSCT), patients are repetitively vaccinated to reduce the risk of infection caused by the immune deficiency following allogeneic HSCT. By the vaccination of transplanted patients, the humoral memory function can be restored in the majority of cases. It is unknown, however, to what extent memory B cells derived from the donor contribute to the mobilization of antibody-secreting cells and long-term humoral memory in patients after allogeneic HSCT. We therefore analyzed patients after allogeneic HSCT for memory B cell responses 7 days after single vaccination against tetanus toxoid (TT), diphtheria toxoid (DT), pertussis toxoid (PT), Haemophilus influenzae type b (Hib), and poliovirus. Patients showed an insufficient mobilization of plasmablasts (PB) after vaccination, whereas healthy subjects (HD, n = 13) exhibited a significant increase of PB in the peripheral blood. Regarding vaccine-specific antibody-secreting PB, all HD responded against all vaccine antigens, as expected. However, only 65% of the patients responded with a measurable increase in IgG-secreting PB against TT, 65% against DT, 33% against PT, and 53% against poliovirus. Correspondingly, the antibody titers on day 7 after vaccination did not increase in patients. A significant increase of serum titers for the vaccine antigens was detectable in the majority of patients only after repetitive vaccinations. In contrast to the low mobilization of vaccine-specific PB after vaccination, a high number of PB before vaccination was detectable in patients following allogeneic HSCT. High frequencies of circulating PB correlated with the incidence of moderate/severe chronic GVHD. In summary, patients showed a weak mobilization of antigen-specific PB and an inadequate increase in antibody titers 7 days after the first vaccination. Patients with moderate or severe chronic GVHD in their history had a significantly higher percentage of IgG-secreting PB prior to vaccination. The antigen specificity of these IgG-secreting PB is currently unknown.
异基因造血干细胞移植（HSCT）后，患者需要反复接种疫苗，以降低异基因 HSCT 后免疫缺陷引起的感染风险。通过对移植患者进行疫苗接种，可以在大多数情况下恢复体液记忆功能。然而，尚不清楚供体来源的记忆 B 细胞在多大程度上有助于动员抗体分泌细胞并在异基因 HSCT 后患者中建立长期的体液记忆。因此，我们分析了异基因 HSCT 后患者在单次破伤风类毒素（TT）、白喉类毒素（DT）、百日咳类毒素（PT）、流感嗜血杆菌 b 型（Hib）和脊髓灰质炎病毒疫苗接种后 7 天的记忆 B 细胞反应。患者在接种疫苗后表现出浆母细胞（PB）动员不足，而健康对照者（HD，n=13）外周血中 PB 显著增加。关于疫苗特异性抗体分泌 PB，所有 HD 均对所有疫苗抗原产生反应，这是预期的。然而，只有 65%的患者对 TT、65%的患者对 DT、33%的患者对 PT 和 53%的患者对脊髓灰质炎病毒 IgG 分泌 PB 的增加有可测量的反应。相应地，患者在接种疫苗后第 7 天的抗体滴度没有增加。只有在重复接种疫苗后，大多数患者的血清疫苗抗原滴度才会显著增加。与接种后疫苗特异性 PB 的低动员相比，异基因 HSCT 后患者在接种前可检测到大量的 PB。循环 PB 的高频率与中度/重度慢性 GVHD 的发生率相关。总之，患者在第一次接种后表现出抗原特异性 PB 的弱动员和抗体滴度的不足增加。有中度或重度慢性 GVHD 病史的患者在接种前 IgG 分泌 PB 的频率明显更高。这些 IgG 分泌 PB 的抗原特异性目前尚不清楚。
