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造血干细胞移植后肺炎的表型、肺部微生物群和细胞因子反应

Phenotypes, Lung Microbiota and Cytokine Responses in Pneumonia After Hematopoietic Stem Cell Transplantation.

作者信息

Hu Yan, Jiang Yanwen, Liu Shuang, Shen Jiawei, An Youzhong

机构信息

Department of Respiratory and Critical Care Medicine, Peking University International Hospital, Beijing, People's Republic of China.

Department of Critical Care Medicine, Peking University People's Hospital, Beijing, People's Republic of China.

出版信息

J Inflamm Res. 2021 Nov 19;14:6055-6065. doi: 10.2147/JIR.S338914. eCollection 2021.

DOI:10.2147/JIR.S338914
PMID:34824541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8610763/
Abstract

OBJECTIVE

We aim to identify phenotypes of hematopoietic stem cell transplantation (HSCT) patients with pneumonia, discover relations of microbiota composition, cytokine profile, and outcomes between phenotypes. Specific cytokines will be evaluated for their role in lung injury in a murine model.

METHODS

HSCT patients with pneumonia were included, and clustering of variables including cytokine levels provided the phenotypes. Outcomes were compared between phenotypes. Analysis of lung microbiota identified marker species of phenotypes. In the murine model, marker species-related cytokine regulations and the role of cytokines in lung injury were evaluated.

RESULTS

Seventy-two patients were included, and two phenotypes were identified, namely "reactive" (N=21) and "nonreactive" (N=51) phenotype. Compared to their counterparts, patients with nonreactive phenotype had lower serum IL-6, IL-8, less severe inflammation, worse outcomes and more viruses as marker species in lung microbiota. The animal study validated the pathogens specific cytokine responses that presented in the human study and the potential protective role of IL-6 in these patients.

CONCLUSION

HSCT patients with pneumonia can be clustered into two phenotypes with different marker species and outcomes: the "nonreactive" phenotype and the "reactive" phenotype. Serum cytokine levels were different between the two phenotypes, which indicate the existence of the pathogen-related cytokine responses. For patients with the "nonreactive" phenotype, IL-6 therapy may improve their prognosis, which should be further tested in clinical studies.

摘要

目的

我们旨在识别造血干细胞移植(HSCT)肺炎患者的表型,发现微生物群组成、细胞因子谱与表型间结局的关系。将在小鼠模型中评估特定细胞因子在肺损伤中的作用。

方法

纳入患有肺炎的HSCT患者,包括细胞因子水平在内的变量聚类提供了表型。比较各表型间的结局。对肺微生物群的分析确定了表型的标志物种类。在小鼠模型中,评估了标志物种类相关的细胞因子调控以及细胞因子在肺损伤中的作用。

结果

纳入72例患者,确定了两种表型,即“反应性”(N = 21)和“无反应性”(N = 51)表型。与“反应性”表型患者相比,“无反应性”表型患者血清白细胞介素-6(IL-6)、白细胞介素-8水平较低,炎症较轻,结局较差,且肺微生物群中作为标志物种类的病毒更多。动物研究验证了人类研究中呈现的病原体特异性细胞因子反应以及IL-6在这些患者中的潜在保护作用。

结论

患有肺炎的HSCT患者可分为具有不同标志物种类和结局的两种表型:“无反应性”表型和“反应性”表型。两种表型间血清细胞因子水平不同,这表明存在病原体相关的细胞因子反应。对于“无反应性”表型的患者,IL-6治疗可能改善其预后,这应在临床研究中进一步测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57f/8610763/cfc30d0b0fc1/JIR-14-6055-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57f/8610763/7aab23a736c4/JIR-14-6055-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57f/8610763/b603bdcd0fad/JIR-14-6055-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57f/8610763/cfc30d0b0fc1/JIR-14-6055-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57f/8610763/7aab23a736c4/JIR-14-6055-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57f/8610763/b603bdcd0fad/JIR-14-6055-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57f/8610763/cfc30d0b0fc1/JIR-14-6055-g0003.jpg

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