Bioinformatic analyses hinted at augmented T helper 17 cell differentiation and cytokine response as the central mechanism of COVID-19-associated Guillain-Barré syndrome.
Bioinformatic analyses hinted at augmented T helper 17 cell differentiation and cytokine response as the central mechanism of COVID-19-associated Guillain-Barré syndrome.
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DOI：
10.1111/cpr.13024
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发表时间：
2021-05
影响因子：
8.5
通讯作者：
Wu WKK
中科院分区：
文献类型：
--
作者：
Li Z;Huang Z;Li X;Huang C;Shen J;Li S;Zhang L;Wong SH;Chan MTV;Wu WKK
格林-巴利综合征（GBS）是由周围神经的自身免疫性攻击引起的，引起感觉、运动和自主神经异常。新出现的证据表明，COVID-19和GBS之间可能存在关联。然而，其潜在的病理生理机制仍不清楚。我们进行了生物信息学分析，以描述COVID-19和GBS之间的潜在遗传串扰。COVID-19和GBS与免疫/炎症调节基因的相似子集相关，包括TNF、CSF 2、IL 2 RA、IL 1B、IL 4、IL 6和IL 10。蛋白质-蛋白质相互作用网络分析显示，与单独的COVID-19或GBS相比，组合的基因集显示出增加的连接性，特别是与CD 86、IL 23 A、IL 27、ISG 20、PTGS 2、HLA-DRB 1、HLA-DQB 1和ITGAM的增强的相互作用，并且这些基因与Th 17细胞分化相关。来自COVID-19和GBS患者的外周血单核细胞的转录组分析进一步证明了两种情况下白细胞介素-17信号传导的激活。在COVID-19和GBS中均发现Th 17细胞分化和细胞因子反应增强。PBMC转录组分析也提示Th 17信号通路的关键参与。总之，我们的数据表明，异常的Th 17细胞分化是COVID-19增加GBS风险的可能机制。通过STRING分析了（A）COVID-19和（B）GBS相关基因的功能性蛋白质-蛋白质关联网络。从DisGeNET（疾病基因组学知识平台）检索与两种疾病实体（COVID-19，疾病ID：C 000657245，版本4，N. PMID ≥ 4; GBS，疾病ID：C 0018378，基因-疾病关联评分≥ 0.02）相关的基因。仅显示了来自“实验”、“数据库”、“共表达”和“共现”的高度置信的相互作用，最低要求的相互作用评分为0.900。网络聚类采用马尔可夫聚类（MLC）算法，其膨胀参数为3.
Guillain‐Barré syndrome (GBS) results from autoimmune attack on the peripheral nerves, causing sensory, motor and autonomic abnormalities. Emerging evidence suggests that there might be an association between COVID‐19 and GBS. Nevertheless, the underlying pathophysiological mechanism remains unclear. We performed bioinformatic analyses to delineate the potential genetic crosstalk between COVID‐19 and GBS. COVID‐19 and GBS were associated with a similar subset of immune/inflammation regulatory genes, including TNF, CSF2, IL2RA, IL1B, IL4, IL6 and IL10. Protein‐protein interaction network analysis revealed that the combined gene set showed an increased connectivity as compared to COVID‐19 or GBS alone, particularly the potentiated interactions with CD86, IL23A, IL27, ISG20, PTGS2, HLA‐DRB1, HLA‐DQB1 and ITGAM, and these genes are related to Th17 cell differentiation. Transcriptome analysis of peripheral blood mononuclear cells from patients with COVID‐19 and GBS further demonstrated the activation of interleukin‐17 signalling in both conditions. Augmented Th17 cell differentiation and cytokine response was identified in both COVID‐19 and GBS. PBMC transcriptome analysis also suggested the pivotal involvement of Th17 signalling pathway. In conclusion, our data suggested aberrant Th17 cell differentiation as a possible mechanism by which COVID‐19 can increase the risk of GBS. Functional protein‐protein association networks of (A) COVID‐19– and (B) GBS‐related genes were analyzed by STRING. Genes associated with the two disease entities (COVID‐19, disease id: C000657245, version 4, N.PMIDs ≥ 4; GBS, disease id: C0018378, Gene‐Disease Association Score ≥ 0.02) were retrieved from DisGeNET, a knowledge platform for disease genomics. Only highly confident interactions derived from ‘Experiments’, ‘Databases’, ‘Co‐expression’ and ‘Co‐occurrence’ with the minimum required interaction score of 0.900 were shown. The Markov cluster (MLC) algorithm with an inflation parameter of 3 was used for network clustering.
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影响因子：
4.6
作者：
Nyati KK;Prasad KN
通讯作者：
Prasad KN
DOI：
10.3390/ijerph17176287
发表时间：
2020-08-28
影响因子：
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作者：
Cancello R;Soranna D;Zambra G;Zambon A;Invitti C
通讯作者：
Invitti C
影响因子：
11.8
作者：
Dandachi, Dima;Geiger, Grant;Chow, Jeremy
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阿托伐他汀通过减少 Th1/Th17 细胞因子和上调 T 调节细胞来改善实验性自身免疫性神经炎
影响因子：
4.3
作者：
Li, Xiao-Li;Dou, Ying-Chun;Duan, Rui-Sheng
通讯作者：
Duan, Rui-Sheng
影响因子：
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Debnath, Monojit;Nagappa, Madhu;Taly, Arun B.
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