Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD
Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD
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不同兔ATG制剂对同种异体HSCT后早期淋巴细胞亚群恢复的影响比较及其与EBV介导的PTLD的关系
DOI：
10.1007/s00432-014-1742-z
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发表时间：
2014
影响因子：
3.6
通讯作者：
Gruhn B
中科院分区：
文献类型：
--
作者：
Mensen A;Häfer R;Meerbach A;Schlecht M;Pietschmann ML;Gruhn B
目的兔抗胸腺细胞球蛋白（ATG）常用于异基因造血干细胞移植（allo-HSCT）前预防移植物抗宿主病。比较不同ATG制剂和剂量对免疫重建的影响以及EB病毒（EBV）介导的移植后淋巴细胞增殖性疾病（PTLD.MethodsIn this retrospective study，we determined T和B cell subsets after allo-HSCT in children，who received ATG-Genzyme（ATG-G，n= 15）、ATG-Fresenius（ATG-F，n= 25）或无ATG治疗（n= 19）。此外，PCR定量的EBV基因组拷贝数与PTLD.ResultsWe的发病率相关，可以确认剂量依赖性损伤的CD 8+和CD 4 +T细胞再生的ATG-G，包括幼稚和记忆的CD 4 + T细胞。在当前施用的剂量5-10 mg/kg ATG-G和20-60 mg/kg ATG-F之间未观察到差异。与ATG-F相比，仅在20-60 mg/kg ATG-G的高剂量下确定了显著延迟的T细胞亚群重建。在ATG-G和ATG-F治疗的患者中，B细胞重建受损。虽然两个ATG组的EBV再激活的发病率是相似的，EBV拷贝数> 104拷贝/105外周血单核细胞和PTLD的发生只发现在ATG-G-treated patients.ConclusionsWe的结论是，高，但重要的是目前没有应用低剂量的ATG-G，损害胸腺T细胞再生和记忆T细胞免疫在更大程度上比ATG-F在儿科患者。此外，我们的研究结果表明，当用ATG-G治疗时，EBV-PTLD的风险增加。前瞻性研究是必要的，以比较不同的ATG制剂的免疫重建和EBV-PTLD。
PurposeRabbit antithymocyte globulin (ATG) is commonly used before allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent graft-versus-host disease. Studies comparing the effect of different ATG preparations and dosages on immune reconstitution and risk for Epstein–Barr virus (EBV)-mediated post-transplant lymphoproliferative disorder (PTLD) are rare.MethodsIn this retrospective study, we determined T and B cell subsets by flow cytometry after allo-HSCT in children, who received ATG-Genzyme (ATG-G,n= 15), ATG-Fresenius (ATG-F,n= 25) or no-ATG treatment (n= 19). Additionally, PCR-quantified EBV-genome copy counts were correlated with incidence of PTLD.ResultsWe could confirm a dose-dependent impairment of CD8+and CD4+T cell regeneration by ATG-G, including naïve and memory CD4+T cells. No differences were seen between the currently applied dosages of 5–10 mg/kg ATG-G and 20–60 mg/kg ATG-F. Significantly delayed T cell subset reconstitution was determined only at high dosages of 20–60 mg/kg ATG-G compared to ATG-F. B cell reconstitution was comparably impaired in ATG-G- and ATG-F-treated patients. Although the incidence of EBV reactivation was similar in both ATG groups, EBV copy counts of >104copies/105peripheral blood mononuclear cells and the occurrence of PTLD were only found in ATG-G-treated patients.ConclusionsWe conclude that high, but importantly not currently applied low dosages of ATG-G, impair thymic T cell regeneration and memory T cell immunity to a greater extent than ATG-F in pediatric patients. In addition, our results suggest an increased risk for EBV-PTLD when treated with ATG-G. Prospective studies are warranted to compare different ATG preparations with regard to the immune reconstitution and EBV-PTLD.
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影响因子：
15.9
作者：
Na, Il-Kang;Lu, Sydney X.;van den Brink, Marcel R. M.
通讯作者：
van den Brink, Marcel R. M.
DOI：
10.3324/haematol.2012.067611
发表时间：
2013-01-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Na, Il-Kang;Wittenbecher, Friedrich;Thiel, Andreas
通讯作者：
Thiel, Andreas
影响因子：
1.9
作者：
Terasako, Kiriko;Sato, Ken;Kanda, Yoshinobu
通讯作者：
Kanda, Yoshinobu
影响因子：
4.8
作者：
Gruhn, B;Meerbach, A;Zintl, F
通讯作者：
Zintl, F
EBV 相关疾病患者临床样本中 Epstein-Barr 病毒 DNA 的半定量 PCR 分析
影响因子：
12.7
作者：
A. Meerbach;B. Gruhn;R. Egerer;U. Reischl;F. Zintl;P. Wutzler
通讯作者：
P. Wutzler