A gut microbiota score predicting acute graft-versus-host disease following myeloablative allogeneic hematopoietic stem cell transplantation

A gut microbiota score predicting acute graft-versus-host disease following myeloablative allogeneic hematopoietic stem cell transplantation
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肠道微生物评分预测清髓性同种异体造血干细胞移植后急性移植物抗宿主病

DOI:
10.1111/ajt.15654
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发表时间:
2019-12-12
影响因子:
8.8
通讯作者:
Peng, Jie
Peng, Jie
中科院分区:
医学2区
文献类型:
--
作者:
Han, Lijie;Zhao, Ke;Peng, Jie

文献摘要

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虽然研究报道肠道微生物群与急性移植物抗宿主病(aGVHD)相关,但缺乏令人满意的预测aGVHD的方法。我们收集了来自两个中心的150例接受清髓性预处理异基因造血干细胞移植(allo-HSCT)的患者在移植后第15天的粪便和血液样本。采用16 S核糖体RNA基因测序法检测粪便菌群;采用多重免疫分析法检测炎性因子;流式细胞术检测T淋巴细胞。开发并验证了来自LASSO(最小绝对收缩和选择算子)模型的肠道微生物群评分(GMS)以预测aGVHD。在发现队列中,GMS可以预测II-IV期aGVHD(受试者操作特征[ROC]曲线下面积[AUC] = 0.904,P < .0001)。此外,验证模型与发现集一致(AUC = 0.887,P < .0001)。低GMS亚组中调节性T/辅助性T细胞17(Treg/Th 17)的比例高于高GMS亚组(P = .012),验证集与发现集一致(P = .003)。此外,高细胞因子水平与高GMS相关。结论中性粒细胞植入时GMS可以预测aGVHD,是一种有潜力的新方法。GMS与炎症因子和Treg/Th 17平衡有关。
Although studies have reported that intestinal microbiota are associated with acute graft-versus-host disease (aGVHD), they lacked a satisfactory method for predicting aGVHD. We collected stool and blood samples at day 15 posttransplant from 150 patients from two centers who underwent myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT). Stool microbiota were detected by 16S ribosomal RNA gene sequencing; inflammatory factors and T lymphocytes were detected by multiplex immunoassays and flow cytometry, respectively. A gut microbiota score (GMS) from a LASSO (least absolute shrinkage and selection operator) model was developed and validated to predict aGVHD. In the discovery cohort, the GMS could predict II-IV aGVHD (area under the receiver operating characteristic [ROC] curve [AUC] = 0.904, P < .0001). Furthermore, the validation model was consistent with the discovery set (AUC = 0.887, P < .0001). Regulatory T/T-helper 17 (Treg/Th17) cells ratio in the low GMS subgroup was higher compared with the high GMS (P = .012), and the validation set is consistent with the discovery set (P = .003). In addition, high cytokine levels were associated with high GMS. In conclusion, the GMS at neutrophil engraftment could predict aGVHD, and it was a potential and novel method. The GMS was associated with the inflammatory factor and Treg/Th17 balance.