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儿童异基因造血干细胞移植后免疫恢复中的胸腺活性

Thymic activity in immune recovery after allogeneic hematopoietic stem cell transplantation in children.

作者信息

Janeczko-Czarnecka MaŁgorzata, Rybka Blanka, Ryczan-Krawczyk Renata, KaŁwak Krzysztof, Ussowicz Marek

机构信息

Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.

出版信息

Cent Eur J Immunol. 2020;45(2):151-159. doi: 10.5114/ceji.2019.89843. Epub 2020 Feb 26.

Abstract

Thymic output was studied prospectively in 52 children who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thymic activity was assessed by quantification of recent thymic emigrants (RTE) discriminated from the rest of naive T cells by immunophenotype CD3+/CD4+/CD31+/CD45RA+. Thymic output was analyzed in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence thymopoiesis: underlying disease, type of HSCT, source of stem cells, age of recipient and donor, type of conditioning, implemented graft versus host disease (GvHD) prophylaxis, viral reactivations (herpes viruses cytomegalovirus - CMV, Epstein-Barr virus - EBV, adenovirus - ADV, BK virus - BKV), occurrence and grade of both acute and chronic graft versus host disease (aGvHD, cGvHD) and number of transplanted CD34 cells/kg. The absolute count of RTE in peripheral blood was evaluated at 6 time points: before the conditioning and on days +15, +30, +60 , +90 and +180 after HSCT. Occurrence of grade II-IV aGvHD was the most important factor associated with low RTE counts after HSCT. History of malignant disease, and transplantation from matched unrelated donor were risk factors for lower thymic output. We found a weak inverse correlation between the age of the recipient and thymic output on post-HSCT day +180. Source of stem cells, type of conditioning, viral reactivations, occurrence of chronic GvHD, age of the donor and the number of transplanted CD34 cells/kg did not affect thymopoiesis in our study group. These preliminary findings and identification of risk factors for deterioration of thymic activity may in the future help in selecting candidates for thymus rejuvenation strategies.

摘要

对52例接受异基因造血干细胞移植(allo-HSCT)的儿童进行了前瞻性胸腺输出研究。通过对近期胸腺迁出细胞(RTE)进行定量来评估胸腺活性,RTE通过免疫表型CD3+/CD4+/CD31+/CD45RA+与其余初始T细胞区分开来。分析胸腺输出与免疫恢复动力学的相关性,并分析其与其他可能影响胸腺生成的潜在风险因素的关系:基础疾病、HSCT类型、干细胞来源、受者和供者年龄、预处理类型、实施的移植物抗宿主病(GvHD)预防措施、病毒再激活(疱疹病毒,如巨细胞病毒 - CMV、EB病毒 - EBV、腺病毒 - ADV、BK病毒 - BKV)、急性和慢性移植物抗宿主病(aGvHD、cGvHD)的发生情况和分级以及每公斤体重移植的CD34细胞数量。在6个时间点评估外周血中RTE的绝对计数:预处理前以及HSCT后第15、30、60、90和180天。发生II-IV级aGvHD是HSCT后RTE计数低的最重要相关因素。恶性疾病史以及来自匹配无关供者的移植是胸腺输出降低的风险因素。我们发现受者年龄与HSCT后第180天的胸腺输出之间存在微弱的负相关。在我们的研究组中,干细胞来源、预处理类型、病毒再激活、慢性GvHD的发生、供者年龄以及每公斤体重移植的CD34细胞数量均未影响胸腺生成。这些初步发现以及胸腺活性恶化风险因素的识别未来可能有助于选择胸腺恢复策略的候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e4f/7792432/3b9160733163/CEJI-45-38630-g001.jpg

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