Department of Pediatrics, Asan Medical Center Children's hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Pediatrics, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.
PLoS One. 2021 Feb 5;16(2):e0246191. doi: 10.1371/journal.pone.0246191. eCollection 2021.
The dynamics of recovery of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) and its impact on controlling clinically significant CMV infections following hematopoietic stem cell transplant (HSCT) are rarely reported in pediatric HSCT recipients. In this study, dynamics of recovery of CMV-specific CMI and its clinical significance in controlling CMV viremia and clinically significant CMV infections were assessed in pediatric allogeneic HSCT recipients. All subjects underwent CMV pp65- and IE1-specific enzyme-linked immune absorbent spot (ELISPOT) assays just before transplantation and then monthly until the detection of CMV-specific CMI with ≥ 5 spot-forming cells (SFC) / 2.0 × 105 cells. Clinically significant CMV infections were defined as CMV diseases, prolonged CMV infections, recurrent CMV infections or late onset CMV infections. Among 52 recipients, 88.5% of recipients recovered CMV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cells at a median of 34 days (interquartile range [IQR]: 29-95 days) following HSCT, 55.8% at 30 days following HSCT, and 73.1% at 90 days following HSCT. The presence of CMV-specific CMI before HSCT was the significant factors for the reconstitution of CMV specific CMI after HSCT (adjusted odds ratio [aOR] = 13.33; 95% confidence interval [CI] = 1.21-142.86). After HSCT, 30 recipients experienced CMV viremia, of which 20 were clinically significant CMV infections. The full recovery of CMV-specific CMI with ≥ 50 SFC / 2.0 × 105 cells after HSCT was the protective factor for the development of clinically significant CMV infections (aOR = 0.13; 95% CI = 0.22-0.71). In the haploidentical HSCT recipients, 82.1% recovered CMV-specific CMI at a median of 65 days after HSCT (IQR: 34-118 days) with a tendency to recover their CMV-specific CMI later than did those from non-haploidentical donors (65 days vs. 30 days; P = 0.001). Clinically significant CMV infections tended to occur more frequently in the haploidentical HSCT recipients compared to those with matched donor HSCT (46.4% vs. 29.2%; P = 0.205). The full recovery of CMV-specific CMI with ≥ 50 SFC/2.0 × 105 cells after HSCT also lowered the risk of development of clinically significant CMV infections (aOR = 0.08; 95% CI = 0.01-0.90). However, transplantation from haploidentical donors was a significant risk factor hampering recovery of CMV-specific CMI (aOR = 0.08; 95% CI = 0.01-0.86) and full recovery of CMV-specific CMI (aOR = 0.05; 95% CI = 0.01-0.50). Pre-transplant CMV-specific CMI influenced the recovery of CMV-specific CMI, and the full recovery of CMV-specific CMI could be a surrogate marker for preventing clinically significant CMV infections in pediatric HSCT recipients. Immunologic monitoring using ELISPOT assay before and after HSCT helps in identifying patients with a high risk of CMV infection and in controlling CMV infection.
在造血干细胞移植（HSCT）后，巨细胞病毒（CMV）特异性细胞介导免疫（CMI）的恢复动态及其对控制临床显著 CMV 感染的影响在儿科 HSCT 受者中很少报道。在这项研究中，评估了儿科异基因 HSCT 受者中 CMV 特异性 CMI 的恢复动态及其在控制 CMV 病毒血症和临床显著 CMV 感染中的临床意义。所有患者在移植前均接受 CMV pp65 和 IE1 特异性酶联免疫吸附斑点（ELISPOT）检测，然后每月进行一次检测，直到检测到 CMV 特异性 CMI 时，其≥5 个斑点形成细胞（SFC）/2.0×105 个细胞。临床显著的 CMV 感染定义为 CMV 疾病、CMV 感染延长、CMV 感染复发或迟发性 CMV 感染。在 52 例受者中，88.5%的受者在 HSCT 后中位 34 天（29-95 天）时恢复了 CMV 特异性 CMI，≥5 SFC/2.0×105 个细胞，HSCT 后 30 天恢复了 55.8%，90 天恢复了 73.1%。HSCT 前存在 CMV 特异性 CMI 是 HSCT 后重建 CMV 特异性 CMI 的显著因素（调整后的优势比[aOR]=13.33；95%置信区间[CI]=1.21-142.86）。HSCT 后，30 例患者发生 CMV 病毒血症，其中 20 例为临床显著的 CMV 感染。HSCT 后 CMV 特异性 CMI 完全恢复至≥50 SFC/2.0×105 个细胞是预防临床显著 CMV 感染发生的保护因素（aOR=0.13；95%CI=0.22-0.71）。在单倍体相合 HSCT 受者中，82.1%的患者在 HSCT 后中位 65 天（34-118 天）时恢复了 CMV 特异性 CMI，与非单倍体相合供者相比，恢复 CMV 特异性 CMI 的趋势较晚（65 天比 30 天；P=0.001）。与匹配供者 HSCT 相比，单倍体相合 HSCT 受者临床显著 CMV 感染的发生率较高（46.4%比 29.2%；P=0.205）。HSCT 后 CMV 特异性 CMI 完全恢复至≥50 SFC/2.0×105 个细胞也降低了发生临床显著 CMV 感染的风险（aOR=0.08；95%CI=0.01-0.90）。然而，来自单倍体相合供者的移植是阻碍 CMV 特异性 CMI 恢复的显著危险因素（aOR=0.08；95%CI=0.01-0.86）和 CMV 特异性 CMI 完全恢复的危险因素（aOR=0.05；95%CI=0.01-0.50）。移植前 CMV 特异性 CMI 影响 CMV 特异性 CMI 的恢复，CMV 特异性 CMI 的完全恢复可能是预防儿科 HSCT 受者临床显著 CMV 感染的替代标志物。HSCT 前后使用 ELISPOT 检测进行免疫监测有助于识别 CMV 感染风险较高的患者，并控制 CMV 感染。
