"Age Related Differences in the Biology of Chronic Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation".
"Age Related Differences in the Biology of Chronic Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation".
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DOI：
10.3389/fimmu.2020.571884
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发表时间：
2020
影响因子：
7.3
通讯作者：
Schultz KR
中科院分区：
文献类型：
--
作者：
Cuvelier GDE;Li A;Drissler S;Kariminia A;Abdossamadi S;Rozmus J;Chanoine JP;Ng B;Mostafavi S;Brinkman RR;Schultz KR
已经确定，与成人相比，儿科造血干细胞移植（HSCT）受者的慢性移植物抗宿主病（cGvHD）发生率较低。我们的研究小组之前已经发表了与临床明确定义的成人和儿童HSCT队列的cGvHD相关的免疫特征变化。由于所有分析都是由同一研究小组进行的，并使用相同的方法进行分析，因此我们首先比较了成人和儿童之前的免疫谱分析。然后，我们进行了额外的分析，比较了不同年龄组的T细胞群，并对我们的儿科队列中HSCT时估计的青春期状态的影响进行了子分析。在所有分析中，我们校正了临床协变量，包括全身照射和cGvHD发作时间。在儿童和成人中观察到三个一致的结果，包括ST 2和幼稚辅助T（Th）细胞的升高和NKreg细胞的抑制。然而，儿童和成人之间在某些细胞因子、B细胞和Treg群体中存在显著差异。在儿童中，我们观察到新形成的B（NF-B）细胞受到广泛抑制，而成人中T1-CD 21 lo B细胞增加，T1-CD 24 hiCD 38 hi B细胞减少。青春期前儿童的氨基肽酶N（sCD 13）和ICAM-1升高。儿童Treg异常似乎主要发生在记忆Treg细胞中，而成人Treg异常发生在幼稚Treg细胞中。在成人中，幼稚Treg和幼稚Th细胞中PD 1表达的丧失与cGvHD相关。我们讨论了这些年龄相关差异的可能机制，以及它们在理论上如何影响儿童和成人之间cGvHD的不同治疗方法。
It is established that pediatric hematopoietic stem cell transplant (HSCT) recipients have a lower rate of chronic graft-versus-host disease (cGvHD) compared to adults. Our group has previously published immune profiles changes associated with cGvHD of clinically well-defined adult and pediatric HSCT cohorts. Since all analyses were performed by the same research group and analyzed using identical methodology, we first compared our previous immune profile analyses between adults and children. We then performed additional analyses comparing the T cell populations across age groups, and a sub-analysis of the impact of the estimated pubertal status at time of HSCT in our pediatric cohort. In all analyses, we corrected for clinical covariates including total body irradiation and time of onset of cGvHD. Three consistent findings were seen in both children and adults, including elevations of ST2 and naive helper T (Th) cells and depression of NKreg cells. However, significant differences exist between children and adults in certain cytokines, B cell, and Treg populations. In children, we saw a broad suppression of newly formed B (NF-B) cells, whereas adults exhibited an increase in T1-CD21lo B cells and a decrease in T1-CD24hiCD38hi B cells. Prepubertal children had elevations of aminopeptidase N (sCD13) and ICAM-1. Treg abnormalities in children appeared to be primarily in memory Treg cells, whereas in adults the abnormalities were in naïve Treg cells. In adults, the loss of PD1 expression in naïve Treg and naïve Th cells was associated with cGvHD. We discuss the possible mechanisms for these age-related differences, and how they might theoretically impact on different therapeutic approaches to cGvHD between children and adults.