T cell receptor β repertoires in patients with COVID-19 reveal disease severity signatures.
T cell receptor β repertoires in patients with COVID-19 reveal disease severity signatures.
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DOI：
10.3389/fimmu.2023.1190844
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
对严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的免疫反应对于维持保护作用和推动2019冠状病毒病（COVID-19）进展的有害病理反应之间的微妙平衡至关重要。T细胞在适应性抗病毒免疫应答中发挥重要作用，因此研究不同疾病严重程度的COVID-19患者中SARS-CoV-2特异性T细胞应答的异质性和多样性是有价值的。在这项研究中，我们采用高通量T细胞受体（TCR）β库测序分析了192名COVID-19患者（包括中度、重度或危重症状患者）外周血中的TCR谱，并将其与81名健康对照进行了比较。我们特别关注SARS-CoV-2相关的TCR克隆型。我们观察到，与健康对照组相比，COVID-19患者的TCR克隆型多样性降低。然而，优势克隆的总体丰度随着疾病的严重程度而增加。此外，我们发现患者组之间的可变（V），连接（J）和VJ配对的基因组重排存在显著差异。此外，我们发现的SARS-CoV-2相关TCR能够准确区分COVID-19患者和健康对照（AUC > 0.98），并将中度症状与更严重形式的疾病（AUC > 0.8）区分开来。这些发现表明，TCR库可以作为监测COVID-19进展的信息生物标志物。我们的研究为TCR库特征提供了有价值的见解，可用于评估宿主对COVID-19的免疫力。这些发现对于使用TCR β库监测疾病发展和指示疾病严重程度具有重要意义。
The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. In this study, we employed high-throughput T cell receptor (TCR) β repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR β repertoires in monitoring disease development and indicating disease severity.
影响因子：
2.6
作者：
Volkan E
通讯作者：
Volkan E
影响因子：
5.6
作者：
Chu R;van Eeden C;Suresh S;Sligl WI;Osman M;Cohen Tervaert JW
通讯作者：
Cohen Tervaert JW