SARS-CoV-2 阳性支气管肺泡灌洗液的不同基因表达:病例系列。

IF 3.5 4区 医学 Q3 CELL BIOLOGY
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-07-25 DOI:10.1159/000532057
Jasmin D Haslbauer, Spasenija Savic Prince, Anna K Stalder, Matthias S Matter, Carl P Zinner, Kathleen Jahn, Ellen Obermann, Jasmin Hanke, Karoline Leuzinger, Hans H Hirsch, Alexandar Tzankov
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引用次数: 0

摘要

背景:目前,COVID-19患者支气管肺泡灌洗液(BAL)的转录组数据十分稀少:本病例系列旨在描述 COVID-19 的肺泡内免疫病理学特征:方法:对 14 例患者(5 例 COVID-19,其中 3 例轻度,2 例基本无症状,9 例对照)进行了肺泡灌洗液检查。对照组包括哮喘(1 例)、BAL 无异常(3 例)、呼吸道合胞病毒感染(1 例)、乙型流感(1 例)和其他冠状病毒感染(3 例)。SARS-CoV-2 RNA 量通过核酸定量检测进行测量,而其他病原体的检测则通过免疫荧光或多重 NAT 进行:基因表达谱分析显示,与对照组相比,SARS-CoV-2 阳性灌洗液中有 71 个转录本明显下调,5 个转录本上调。下调的转录本包括参与巨噬细胞发育、极化和串联的基因(LGALS3、MARCO、ERG2、BTK、RAC1、CD83),以及参与趋化因子信号转导和免疫代谢的基因(NUPR1、CEBPB、CEBPA、PECAM1、CCL18、PPARG、ALOX5、ALOX5AP)。转录本上调的基因主要涉及 NK-T 细胞信号传导(GZMA、GZMH、GNLY、PRF1、CD3G)。与无症状病例相比,轻度 COVID-19 患者体内涉及血液单核细胞/白细胞功能(G0S2、ANXA6、FCGR2B、ADORA3)、凝血(von Willebrand factor [VWF])、干扰素反应(IFRD1、IL12RB2)和哮喘中升高的锌金属蛋白酶(CPA3)的基因明显上调。将5例COVID-19 BAL病例与已发表的COVID-19致死病例队列进行了分子内比较,结果显示致死病例的 "抗原处理和递呈 "及 "溶酶体 "通路显著上调:这些数据强调了 COVID-19 免疫反应的异质性。要想更好地了解 SARS-CoV-2 免疫反应的特征,还需要对更大的数据集进行进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series.

Background: Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce.

Objectives: This case series seeks to characterize the intra-alveolar immunopathology of COVID-19.

Method: BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n = 1), unremarkable BALs (n = 3), infections with respiratory syncytial virus (n = 1), influenza B (n = 1), and infections with other coronaviruses (n = 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while the detection of other pathogens was performed by immunofluorescence or multiplex NAT.

Results: Gene expression profiling showed 71 significantly downregulated and 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated transcripts included genes involved in macrophage development, polarization, and crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), and genes involved in chemokine signaling and immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated transcripts featured genes involved in NK-T cell signaling (GZMA, GZMH, GNLY, PRF1, CD3G). Patients with mild COVID-19 showed a significant upregulation of genes involved in blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), and a zinc metalloprotease elevated in asthma (CPA3) compared to asymptomatic cases. In-silico comparison of the 5 COVID-19 BAL cases to a published cohort of lethal COVID-19 showed a significant upregulation of "antigen processing and presentation" and "lysosome" pathways in lethal cases.

Conclusions: These data underscore the heterogeneity of immune response in COVID-19. Further studies with a larger dataset are required to gain a better understanding of the hallmarks of SARS-CoV-2 immunological response.

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来源期刊
Pathobiology
Pathobiology 医学-病理学
CiteScore
8.50
自引率
0.00%
发文量
47
审稿时长
>12 weeks
期刊介绍: ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.
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