个体和基因型并非决定新冠病毒疾病严重程度的主要因素。

Individual , and Genotypes Are No Major Factors Which Determine COVID-19 Severity.

作者信息

Schetelig Johannes, Heidenreich Falk, Baldauf Henning, Trost Sarah, Falk Bose, Hoßbach Christian, Real Ruben, Roers Axel, Lindemann Dirk, Dalpke Alexander, Kolditz Martin, de With Katja, Bornhäuser Martin, Bonifacio Ezio E, Rücker-Braun Elke, Lange Vinzenz, Markert Jan, Barth Ralf, Hofmann Jan A, Sauter Jürgen, Bernas Stefanie N, Schmidt Alexander H

机构信息

Clinical Trials Unit, DKMS, Dresden, Germany.

Division of Hematology, Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität (TU), Dresden, Dresden, Germany.

出版信息

Front Immunol. 2021 Jul 26;12:698193. doi: 10.3389/fimmu.2021.698193. eCollection 2021.

Abstract

HLA molecules are key restrictive elements to present intracellular antigens at the crossroads of an effective T-cell response against SARS-CoV-2. To determine the impact of the genotype on the severity of SARS-CoV-2 courses, we investigated data from 6,919 infected individuals. HLA-A, -B, and -DRB1 allotypes grouped into HLA supertypes by functional or predicted structural similarities of the peptide-binding grooves did not predict COVID-19 severity. Further, we did not observe a heterozygote advantage or a benefit from HLA diplotypes with more divergent physicochemical peptide-binding properties. Finally, numbers of predicted viral T-cell epitopes did not correlate with the severity of SARS-CoV-2 infections. These findings suggest that the genotype is no major factor determining COVID-19 severity. Moreover, our data suggest that the spike glycoprotein alone may allow for abundant T-cell epitopes to mount robust T-cell responses not limited by the genotype.

摘要

HLA分子是在针对SARS-CoV-2的有效T细胞反应的交叉点上呈递细胞内抗原的关键限制因素。为了确定基因型对SARS-CoV-2病程严重程度的影响,我们调查了6919名感染者的数据。根据肽结合槽的功能或预测结构相似性分组为HLA超型的HLA-A、-B和-DRB1等位基因不能预测COVID-19的严重程度。此外,我们没有观察到杂合子优势或具有更多不同理化肽结合特性的HLA单倍型带来的益处。最后,预测的病毒T细胞表位数量与SARS-CoV-2感染的严重程度无关。这些发现表明,基因型不是决定COVID-19严重程度的主要因素。此外,我们的数据表明,仅刺突糖蛋白就可能产生大量T细胞表位,从而引发不受基因型限制的强大T细胞反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/136e/8350391/3c3c75cee323/fimmu-12-698193-g001.jpg

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