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造血干细胞移植的不良反应与人类白细胞抗原区域内的基因多态性有关。

The adverse events of haematopoietic stem cell transplantation are associated with gene polymorphism within human leukocyte antigen region.

机构信息

Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan City, 333, Taiwan.

Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan County, Taiwan.

出版信息

Sci Rep. 2021 Jan 14;11(1):1475. doi: 10.1038/s41598-020-79369-w.

DOI:10.1038/s41598-020-79369-w
PMID:33446692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7809291/
Abstract

Adverse reactions may still occur in some patients after receiving haematopoietic stem cell transplantation (HSCT), even when choosing a human leukocyte antigen (HLA)-matched donor. The adverse reactions of transplantation include disease relapse, graft-versus-host disease (GVHD), mortality and CMV infection. However, only the relapse was discussed in our previous study. Therefore, in this study, we investigated the correlation between the gene polymorphisms within the HLA region and the adverse reactions of post-HSCT in patients with acute leukaemia (n = 176), where 72 patients were diagnosed with acute lymphocytic leukaemia (ALL) and 104 were acute myeloid leukaemia (AML). The candidate single nucleotide polymorphisms were divided into three models: donor, recipient, and donor-recipient pairs and the data of ALL and AML were analysed individually. Based on the results, we found 16 SNPs associated with the survival rates, the risk of CMV infection, or the grade of GVHD in either donor, recipient, or donor-recipient matching models. In the ALL group, the rs209132 of TRIM27 in the donor group was related to CMV infection (p = 0.021), the rs213210 of RING1 in the recipient group was associated with serious GVHD (p = 0.003), and the rs2227956 of HSPA1L in the recipient group correlated with CMV infection (p = 0.001). In the AML group, the rs3130048 of BAG6 in the donor-recipient pairs group was associated with serious GVHD (p = 0.048). Moreover, these SNPs were further associated with the duration time of survival after transplantation. These results could be applied to select the best donor in HSCT.

摘要

移植后即使选择了人类白细胞抗原(HLA)匹配的供体,一些患者仍可能出现不良反应。移植的不良反应包括疾病复发、移植物抗宿主病(GVHD)、死亡率和 CMV 感染。然而,在我们之前的研究中仅讨论了复发。因此,在这项研究中,我们调查了急性白血病(n=176)患者中 HLA 区域内基因多态性与 HSCT 后不良反应的相关性,其中 72 例患者被诊断为急性淋巴细胞白血病(ALL),104 例为急性髓细胞白血病(AML)。候选单核苷酸多态性分为三种模型:供体、受体和供体-受体对,单独分析 ALL 和 AML 的数据。基于结果,我们发现 16 个 SNP 与供体、受体或供体-受体匹配模型中的生存率、CMV 感染风险或 GVHD 严重程度相关。在 ALL 组中,供体组的 TRIM27 中的 rs209132 与 CMV 感染有关(p=0.021),受体组的 RING1 中的 rs213210 与严重 GVHD 相关(p=0.003),受体组的 HSPA1L 中的 rs2227956 与 CMV 感染相关(p=0.001)。在 AML 组中,供体-受体对中的 rs3130048 与严重 GVHD 相关(p=0.048)。此外,这些 SNP 与移植后生存时间的持续时间进一步相关。这些结果可用于选择 HSCT 中最佳的供体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/1b91f347cf41/41598_2020_79369_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/aee1728af1dc/41598_2020_79369_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/2d1a3a1efd7a/41598_2020_79369_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/8effbd5e438b/41598_2020_79369_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/1b91f347cf41/41598_2020_79369_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/aee1728af1dc/41598_2020_79369_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/2d1a3a1efd7a/41598_2020_79369_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/8effbd5e438b/41598_2020_79369_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bec/7809291/1b91f347cf41/41598_2020_79369_Fig4_HTML.jpg

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