高度多重免疫组库测序将多种淋巴细胞类别与COVID-19的反应严重程度联系起来。
Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19.
作者信息
Dannebaum Richard, Suwalski Phillip, Asgharian Hosseinali, Du Zhipei Gracie, Lin Hai, Weiner January, Holtgrewe Manuel, Thibeault Charlotte, Müller Melina, Wang Xiaomin, Karadeniz Zehra, Saccomanno Jacopo, Doehn Jan-Moritz, Hübner Ralf-Harto, Hinzmann Bernd, Blüher Anja, Siemann Sandra, Telman Dilduz, Suttorp Norbert, Witzenrath Martin, Hippenstiel Stefan, Skurk Carsten, Poller Wolfgang, Sander Leif E, Beule Dieter, Kurth Florian, Guettouche Toumy, Landmesser Ulf, Berka Jan, Luong Khai, Rubelt Florian, Heidecker Bettina
机构信息
Roche Sequencing Solutions Pleasanton, CA 94588, United States.
Department of Cardiology, Charité Universitätsmedizin Berlin, Berlin, DE 10117, Germany.
出版信息
EClinicalMedicine. 2022 Jun;48:101438. doi: 10.1016/j.eclinm.2022.101438. Epub 2022 May 14.
BACKGROUND
Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response.
METHODS
In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19.
FINDINGS
Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple lymphocyte classes in disease progression.
INTERPRETATION
Adaptive immune receptor peripheral blood repertoire measures are associated with COVID-19 disease severity.
FUNDING
The study was funded with grants from the Berlin Institute of Health (BIH).
背景
2019冠状病毒病（COVID-19）患者的疾病进展差异很大。了解对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的各种免疫反应类型对于更好地临床管理冠状病毒疫情以及潜在改善未来治疗至关重要。疾病动态可以通过解读适应性免疫反应来表征。
方法
在这项横断面研究中，我们分析了117份来自健康对照者以及轻度至重度COVID-19患者的外周血免疫组库，以阐明B细胞和T细胞之间的相互作用。我们使用免疫组库引物延伸靶向富集方法（immunoPETE）同时对人类白细胞抗原（HLA）限制性T细胞受体β链（TRB）、非限制性T细胞受体δ链（TRD）和免疫球蛋白重链（IgH）免疫受体组库进行测序。分析了健康受试者和COVID-19感染受试者之间TRB、TRD和IgH克隆的分布情况。使用麦克法登调整R2检验变量以建立预测模型。本研究的目的是分析适应性免疫组库对COVID-19疾病严重程度（世界卫生组织临床进展量表上的值）的影响。
研究结果
将临床元数据与三种免疫受体重链（TRB、TRD和IgH）的克隆型相结合，我们发现COVID-19疾病严重程度组与B细胞和T细胞区室的免疫受体序列之间存在显著关联。逻辑回归显示，重度COVID-19患者中共享IgH克隆型增加，TRD减少。在健康受试者（对照组）中发现TRD克隆型共享克隆的概率最高。一些特定的TRB克隆似乎存在于重度COVID-19患者中（图S7b）。信息量最大的模型（麦克法登调整R² = 0.141）将疾病严重程度与所有三种细胞类型的免疫组库指标以及受体特异性细胞计数联系起来，突出了多种淋巴细胞类别在疾病进展中的重要性。
解读
适应性免疫受体外周血组库指标与COVID-19疾病严重程度相关。
资金来源
本研究由柏林健康研究所（BIH）的资助。
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