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基因多态性对急性移植物抗宿主病和异基因造血干细胞移植受者生存的影响:白细胞介素 10 基因多态性作为一种更易接近的预测预后的靶点。

The effects of gene polymorphisms on susceptibility to acute GVHD and survival of allogeneic HSCT recipients: IL-10 gene polymorphisms as a more accessible target to predict prognosis.

机构信息

Graduate Program in Child and Adolescent Health, Federal University of Rio Grande, do Sul/UFRGS, Brazil; Hospital de Clínicas de Porto Alegre/HCPA, Brazil.

Hospital de Clínicas de Porto Alegre/HCPA, Brazil.

出版信息

Hum Immunol. 2020 Jan;81(1):18-25. doi: 10.1016/j.humimm.2019.12.002. Epub 2019 Dec 27.

DOI:10.1016/j.humimm.2019.12.002
PMID:31889553
Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic modality commonly used to treat hematological and immunological disorders. Among the main complications of allo-HSCT is the acute graft-versus-host disease (a-GVHD), a condition which accounts for a high incidence of mortality. Several genes encoding inflammatory mediators may present polymorphisms, which have been implicated in the risk of developing a-GVHD. In our study, we investigated the association between genotypes of cytokine-encoding genes and the incidence and severity of a-GVHD and survival of HSCT recipients. No statistically significant association was found between IL and 6-174 G/C, INF-γ + 874 T/A, TNF-α -238 A/G, -308 A/G and IL-10-819C/T, -592 A/C polymorphisms and the presence or severity of a-GVHD. A higher risk of a-GVHD was associated with the IL-10-1082 GG genotype compared to the AA + AG genotypes of recipients and donors. The IL-10-1082 genotype can be used as a prognostic determinant to predict which HSCT recipient will be more responsive to the transplant. Thus, cytokine gene assays may be useful in the individualization of prophylactic regimens and for an appropriate selection of immunosuppressants based on the HSCT recipient's responsiveness.

摘要

异基因造血干细胞移植(allo-HSCT)是一种常用于治疗血液和免疫系统疾病的治疗方法。allo-HSCT 的主要并发症之一是急性移植物抗宿主病(a-GVHD),这种疾病的死亡率很高。编码炎症介质的一些基因可能存在多态性,这些多态性与发生 a-GVHD 的风险有关。在我们的研究中,我们调查了细胞因子编码基因的基因型与 a-GVHD 的发生率、严重程度以及 HSCT 受者的存活率之间的关系。未发现 IL 和 6-174 G/C、INF-γ+874T/A、TNF-α-238A/G、-308A/G 和 IL-10-819C/T、-592A/C 多态性与 a-GVHD 的存在或严重程度之间存在统计学显著关联。与受体和供体的 AA+AG 基因型相比,IL-10-1082 GG 基因型与 a-GVHD 的发生风险更高。与 AA+AG 基因型相比,IL-10-1082 基因型与 a-GVHD 的发生风险更高。IL-10-1082 基因型可用作预测 HSCT 受者对移植反应性的预后决定因素。因此,细胞因子基因检测可能有助于个体化预防方案,并根据 HSCT 受者的反应性适当选择免疫抑制剂。

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