在重症 COVID-19 患者的 T 细胞受体中检测到的基因特征。
Genetic signature detected in T cell receptors from patients with severe COVID-19.
作者信息
Corpas Manuel, de Mendoza Carmen, Moreno-Torres Víctor, Pintos Ilduara, Seoane Pedro, Perkins James R, Ranea Juan A G, Fatumo Segun, Korcsmaros Tamas, Martín-Villa José Manuel, Barreiro Pablo, Corral Octavio, Soriano Vicente
机构信息
School of Life Sciences, University of Westminster, London, UK.
Cambridge Precision Medicine Limited, ideaSpace, University of Cambridge Biomedical Innovation Hub, Cambridge, UK.
出版信息
iScience. 2023 Aug 25;26(10):107735. doi: 10.1016/j.isci.2023.107735. eCollection 2023 Oct 20.
Characterization of host genetic factors contributing to COVID-19 severity promises advances on drug discovery to fight the disease. Most genetic analyses to date have identified genome-wide significant associations involving loss-of-function variants for immune response pathways. Despite accumulating evidence supporting a role for T cells in COVID-19 severity, no definitive genetic markers have been found to support an involvement of T cell responses. We analyzed 205 whole exomes from both a well-characterized cohort of hospitalized severe COVID-19 patients and controls. Significantly enriched high impact alleles were found for 25 variants within the T cell receptor beta (TRB) locus on chromosome 7. Although most of these alleles were found in heterozygosis, at least three or more in , , , , and suggested a possible TRB loss of function via compound heterozygosis. This loss-of-function in TRB genes supports suboptimal or dysfunctional T cell responses as a major contributor to severe COVID-19 pathogenesis.
对导致新冠病毒疾病严重程度的宿主遗传因素进行表征，有望推动抗击该疾病的药物研发取得进展。迄今为止，大多数基因分析已确定了全基因组范围内的显著关联，这些关联涉及免疫反应途径的功能丧失变异。尽管越来越多的证据支持T细胞在新冠病毒疾病严重程度中发挥作用，但尚未发现明确的遗传标记来支持T细胞反应的参与。我们分析了来自一组特征明确的住院重症新冠病毒疾病患者和对照组的205份全外显子组。在7号染色体上的T细胞受体β（TRB）基因座内的25个变异中发现了显著富集的高影响等位基因。尽管这些等位基因大多以杂合状态存在，但在 、 、 、 和 中至少有三个或更多表明可能通过复合杂合性导致TRB功能丧失。TRB基因的这种功能丧失支持了次优或功能失调的T细胞反应是重症新冠病毒疾病发病机制的主要促成因素。
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