Bejanyan N, Vlasova-St Louis I, Mohei H, Cao Q, El Jurdi N, Wagner J E, Miller J S, Brunstein C G
Department of Medicine. University of Minnesota, Minneapolis, Minnesota.
Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota.
Transplant Cell Ther. 2021 Feb;27(2):187.e1-187.e4. doi: 10.1016/j.jtct.2020.11.014. Epub 2020 Dec 21.
Rapid quantitative recovery of NK cells but slower recovery of T-cell subsets along with frequent viral infections are reported after umbilical cord blood (UCB) compared with matched sibling donor (MSD) hematopoietic cell transplantation (HCT). However, it remains unclear whether increased propensity for viral infections is also a result of slower recovery of virus-specific immunity after UCB as compared to MSD HCT.
We examined the differences in the function of virus-specific peripheral blood mononuclear cells (PBMC) after UCB (N=17) vs. MSD (N=9) using previously collected patient blood samples at various time points after HCT.
Interferon-gamma (IFN-γ) enzyme-linked immune absorbent spot (ELISpot) assay was used to quantify the PBMC frequencies that secrete IFN-γ in response to 11 immunopeptides from 5 common viruses. We included the patients who received the same reduced intensity conditioning regimen without ATG, no systemic glucocorticoids and had no relapse or acute/chronic graft-versus-host disease within 1 year after HCT.
The CMV-reactive PBMC frequencies were higher in CMV seropositive vs. seronegative patients after HCT. Among CMV seropositive patients, the frequency of CMV-reactive PBMC was lower after UCB compared to MSD throughout one year of HCT. We observed no differences in virus-specific PBMC responses towards HHV6, EBV, BK, and adenovirus antigens between UCB and MSD.
Our data demonstrate that the reconstitution of CMV-specific immunity is slower in CMV seropositive recipients of UCB vs. MSD HCT in contrast to other viruses which had similar recoveries. These study findings support implementation of more potent prophylactic strategies for preventing CMV reactivation in CMV seropositive patients receiving UCB HCT.
与匹配的同胞供体(MSD)造血细胞移植(HCT)相比,脐带血(UCB)移植后报告自然杀伤细胞快速定量恢复,但T细胞亚群恢复较慢,且频繁发生病毒感染。然而,与MSD HCT相比,UCB移植后病毒特异性免疫恢复较慢是否也是病毒感染倾向增加的原因仍不清楚。
我们使用先前收集的HCT后不同时间点的患者血样,研究了UCB(n = 17)与MSD(n = 9)后病毒特异性外周血单个核细胞(PBMC)功能的差异。
采用干扰素-γ(IFN-γ)酶联免疫斑点(ELISpot)试验,对5种常见病毒的11种免疫肽刺激后分泌IFN-γ的PBMC频率进行定量。我们纳入了接受相同减低强度预处理方案、未使用抗胸腺细胞球蛋白、未使用全身糖皮质激素且HCT后1年内无复发或急性/慢性移植物抗宿主病的患者。
HCT后,巨细胞病毒(CMV)血清阳性患者的CMV反应性PBMC频率高于血清阴性患者。在CMV血清阳性患者中,整个HCT一年期间,UCB移植后的CMV反应性PBMC频率低于MSD移植后。我们观察到UCB和MSD之间针对人疱疹病毒6型(HHV6)、EB病毒(EBV)、BK病毒和腺病毒抗原的病毒特异性PBMC反应无差异。
我们的数据表明,与其他恢复情况相似的病毒相比,UCB移植的CMV血清阳性受者与MSD HCT受者相比,CMV特异性免疫重建较慢。这些研究结果支持对接受UCB HCT的CMV血清阳性患者实施更有效的预防CMV再激活的策略。