The T-cell repertoire of Spanish patients with COVID-19 as a strategy to link T-cell characteristics to the severity of the disease.

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY
Fernando Marín-Benesiu, Lucia Chica-Redecillas, Verónica Arenas-Rodríguez, Esperanza de Santiago, Silvia Martínez-Diz, Ginesa López-Torres, Ana Isabel Cortés-Valverde, Catalina Romero-Cachinero, Carmen Entrala-Bernal, Francisco Javier Fernandez-Rosado, Luis Javier Martínez-González, Maria Jesus Alvarez-Cubero
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引用次数: 0

Abstract

Background: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients.

Methods: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19.

Results: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs.

Conclusions: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.

将西班牙 COVID-19 患者的 T 细胞复合物作为将 T 细胞特征与疾病严重程度联系起来的一种策略。
背景:T细胞群的结构和动态对于协调对SARS-CoV-2的免疫反应至关重要。在我们的研究中,我们使用 T 细胞受体测序(TCRseq)研究了 173 例感染后 COVID-19 患者的 TCR 重排:队列包括 98 例轻度病例和 75 例重度病例,中位年龄为 53 岁。我们对 TCR β 链互补决定区 3(CDR3b)进行了扩增和测序,并进行了生物信息学分析,以评估不同年龄、性别和严重程度组间的基因组多样性、克隆性和 V/J 等位基因使用情况。CDR3b氨基酸序列推断是通过对结构基元进行聚类,并将有效的反应性CDR3b筛选到COVID-19中进行的:结果:我们的研究结果表明,在 55 岁以下的 COVID-19 重症患者的 TCR 反应序列中,多样性明显减少,克隆扩增增加。这些结果反映了在 55 岁以上患者(包括轻度和重度患者)中观察到的趋势。此外,我们还发现与疾病严重程度相关的关键 V 等位基因(TRBV14、TRBV19、TRBV15 和 TRBV6-4)的使用率显著降低。值得注意的是,55 岁以下的重症患者的等位基因模式与 55 岁以上的患者相似,伴有 COVID-19 相关基序频率的偏斜:目前的研究结果表明,55 岁以下的重症患者的 TCR 反应谱可能受到影响,从而导致病情恶化。
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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
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