Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity.
Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity.
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DOI：
10.1016/j.celrep.2023.112613
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发表时间：
2023-06-27
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
某些血清蛋白，包括C-反应蛋白（CRP）和D-二聚体，在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）患者中具有预后价值。尽管如此，这些因素是非特异性的，对驱动严重COVID-19发病机制的外周血单核细胞（PBMC）群体提供了有限的机制见解。为了确定与疾病相关的细胞表型，我们对40名未接种SARS-CoV-2疫苗的个体的总PBMC蛋白质组和质膜PBMC蛋白质组进行了全面、无偏的分析，这些个体跨越了整个疾病谱。结合来自相同供体的RNA测序（RNA-seq）和流式细胞术，我们为每个严重程度水平定义了一个全面的多组学特征，揭示了免疫细胞失调随着疾病的增加而进展。细胞表面蛋白CEACAM 1、6和8、CD 177、CD 63和CD 89与严重COVID-19密切相关，对应于非典型CD 3 + CD 4 + CEACAM 1/6/8+ CD 177 + CD 63 + CD 89+和CD 16 + CEACAM 1/6/8+单核细胞的出现。利用这些标志物可以通过流式细胞术促进实时患者评估，并鉴定可以靶向改善免疫病理学的免疫群体。Potts等人描述了对从COVID-19患者中获得的免疫细胞进行的多重蛋白质组学分析，将CEACAM 1/6/8、CD 177、CD 63和CD 89鉴定为在严重疾病中上调的细胞表面标志物。表型鉴定在严重疾病中表达这些标志物的不寻常的CD 4 + T细胞和CD 16+单核细胞群体的出现。
Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. The cell-surface proteins CEACAMs1, 6, and 8, CD177, CD63, and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CEACAM1/6/8+CD177+CD63+CD89+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilization of these markers may facilitate real-time patient assessment by flow cytometry and identify immune populations that could be targeted to ameliorate immunopathology. Potts et al. describe a multiplexed proteomic analysis of immune cells obtained from individuals with COVID-19, identifying CEACAMs 1/6/8, CD177, CD63, and CD89 as cell-surface markers upregulated in severe disease. Phenotyping identifies emergence of unusual CD4+ T cell and CD16+ monocyte populations expressing these markers in severe disease.
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影响因子：
64.5
作者：
COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium. Electronic address: julian.knight@well.ox.ac.uk;COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium
通讯作者：
COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium
影响因子：
64.5
作者：
Huttlin EL;Jedrychowski MP;Elias JE;Goswami T;Rad R;Beausoleil SA;Villén J;Haas W;Sowa ME;Gygi SP
通讯作者：
Gygi SP
DOI：
10.1186/cc14003
发表时间：
2014-08-01
期刊：
Critical care (London, England)
影响因子：
--
作者：
Darcy CJ;Minigo G;Piera KA;Davis JS;McNeil YR;Chen Y;Volkheimer AD;Weinberg JB;Anstey NM;Woodberry T
通讯作者：
Woodberry T
影响因子：
14.9
作者：
Deutsch EW;Csordas A;Sun Z;Jarnuczak A;Perez-Riverol Y;Ternent T;Campbell DS;Bernal-Llinares M;Okuda S;Kawano S;Moritz RL;Carver JJ;Wang M;Ishihama Y;Bandeira N;Hermjakob H;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin