RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.
RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.
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DOI：
10.1093/cid/ciw767
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发表时间：
2017-02-15
期刊：
影响因子：
--
通讯作者：
Complex Chronic Disease Study Group
中科院分区：
文献类型：
--
作者：
Bouquet J;Gardy JL;Brown S;Pfeil J;Miller RR;Morshed M;Avina-Zubieta A;Shojania K;McCabe M;Parker S;Uyaguari M;Federman S;Tang P;Steiner T;Otterstater M;Holt R;Moore R;Chiu CY;Patrick DM;Complex Chronic Disease Study Group
在慢性疲劳综合征或另外诊断的慢性莱姆综合征患者和对照之间，没有发现血液转录组、病毒组和 B 细胞/T 细胞受体模式存在差异。没有发现这两种疾病与转录介导的免疫功能障碍或活性病毒感染有关。慢性疲劳综合症（CFS）仍然知之甚少。尽管推测感染会引发该综合征，但具体的感染因子和潜在的病理生理机制仍然难以捉摸。在之前的一项研究中，我们描述了 CFS 患者和替代诊断的慢性莱姆综合征 (ADCLS) 患者的相似临床表型，这些患者通过私人莱姆专业实验室检测诊断为莱姆病，但通过参考 2 级血清学分析检测呈阴性。在这里，我们对从 25 名诊断为 CFS 的成人和 13 名 ADCLS 患者收集的全血进行了盲法 RNA 测序分析，将这些病例与 25 名匹配对照者和 11 名控制良好的系统性红斑狼疮 (SLE) 患者进行比较。样本是在患者登记时收集的，而不是在急性症状发作期间收集的。 RNA-seq 数据用于研究宿主基因表达、B 细胞/T 细胞受体谱 (BCR/TCR) 和潜在的病毒感染。当 CFS 或 ADCLS 病例与对照进行比较时，没有发现显着的差异表达基因 (DEG)。当将 SLE 病例与对照进行比较时，发现了 42 个 DEG，这与与 SLE 疾病相关的干扰素信号通路的激活一致。 BCR/TCR 谱分析未显示 CFS 与对照或 ADCLS 与对照之间存在显着差异。最后，在 RNA-seq 数据中检测到与指环病毒、人类 Pegivirus 1、疱疹病毒和乳头瘤病毒相对应的病毒序列，但所有属级分类类别的比例相似 (P = .73)。我们的观察结果不支持 CFS 和 ADCLS 中转录介导的免疫细胞失调的理论，至少在急性症状发作期之外是这样。
No differences in blood transcriptome, virome, and B-cell/T-cell receptor patterns were found between chronic fatigue syndrome or alternatively diagnosed chronic Lyme syndrome patients and controls. Neither disease was found to be associated with transcriptionally mediated immune dysfunction or active viral infection. Chronic fatigue syndrome (CFS) remains poorly understood. Although infections are speculated to trigger the syndrome, a specific infectious agent and underlying pathophysiological mechanism remain elusive. In a previous study, we described similar clinical phenotypes in CFS patients and alternatively diagnosed chronic Lyme syndrome (ADCLS) patients—individuals diagnosed with Lyme disease by testing from private Lyme specialty laboratories but who test negative by reference 2-tiered serologic analysis. Here, we performed blinded RNA-seq analysis of whole blood collected from 25 adults diagnosed with CFS and 13 ADCLS patients, comparing these cases to 25 matched controls and 11 patients with well-controlled systemic lupus erythematosus (SLE). Samples were collected at patient enrollment and not during acute symptom flares. RNA-seq data were used to study host gene expression, B-cell/T-cell receptor profiles (BCR/TCR), and potential viral infections. No differentially expressed genes (DEGs) were found to be significant when CFS or ADCLS cases were compared to controls. Forty-two DEGs were found when SLE cases were compared to controls, consistent with activation of interferon signaling pathways associated with SLE disease. BCR/TCR repertoire analysis did not show significant differences between CFS and controls or ADCLS and controls. Finally, viral sequences corresponding to anelloviruses, human pegivirus 1, herpesviruses, and papillomaviruses were detected in RNA-seq data, but proportions were similar (P = .73) across all genus-level taxonomic categories. Our observations do not support a theory of transcriptionally mediated immune cell dysregulation in CFS and ADCLS, at least outside of periods of acute symptom flares.
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作者：
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