Identification of Robust Protein Associations With COVID-19 Disease Based on Five Clinical Studies.
Identification of Robust Protein Associations With COVID-19 Disease Based on Five Clinical Studies.
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DOI：
10.3389/fimmu.2021.781100
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发表时间：
2021
影响因子：
7.3
通讯作者：
Schmidt F
中科院分区：
文献类型：
--
作者：
Suhre K;Sarwath H;Engelke R;Sohail MU;Cho SJ;Whalen W;Alvarez-Mulett S;Krumsiek J;Choi AMK;Schmidt F
多项研究使用 Olink 亲和蛋白质组学平台研究了血液循环蛋白在 COVID-19 疾病中的作用。然而，研究之间的研究纳入标准和样本收集条件各不相同，导致有时存在不一致的关联。为了确定疾病最强大的蛋白质标记以及在所有条件下相关的潜在途径，必须确定复制最广泛的蛋白质。在这里，我们将两项新招募的 COVID-19 研究（N=68 和 N=98）的 Olink 蛋白质组学概况与之前发表的三项 COVID-19 研究（N=383、N=83、N=57）的蛋白质组学概况结合起来。在这些研究中，对具有 253 种独特蛋白质的三个 Olink 组合（炎症和心血管 II 和 III）进行了比较。病例/对照分析显示，在所有五项研究中，13 种蛋白质（CCL16、CCL7、CXCL10、CCL8、LGALS9、CXCL11、IL1RN、CCL2、CD274、IL6、IL18、MERTK、IFNγ 和 IL18R1）在 COVID-19 患者中存在差异表达。除了在对照组中较高的 CCL16 外，所有蛋白质在 COVID-19 患者中均过度表达。通路分析揭示了所有研究中与细胞因子-细胞因子相互作用、IL18 信号传导、液体剪切应力和类风湿关节炎相关通路的一致趋势。我们的结果重申了之前与 COVID-19 细胞因子风暴综合征相关的发现。 COVID-19 特异性蛋白质表达谱的交叉研究稳健性支持亲和蛋白质组学作为工具和识别潜在治疗靶点的实用性。
Multiple studies have investigated the role of blood circulating proteins in COVID-19 disease using the Olink affinity proteomics platform. However, study inclusion criteria and sample collection conditions varied between studies, leading to sometimes incongruent associations. To identify the most robust protein markers of the disease and the underlying pathways that are relevant under all conditions, it is essential to identify proteins that replicate most widely. Here we combined the Olink proteomics profiles of two newly recruited COVID-19 studies (N=68 and N=98) with those of three previously published COVID-19 studies (N=383, N=83, N=57). For these studies, three Olink panels (Inflammation and Cardiovascular II & III) with 253 unique proteins were compared. Case/control analysis revealed thirteen proteins (CCL16, CCL7, CXCL10, CCL8, LGALS9, CXCL11, IL1RN, CCL2, CD274, IL6, IL18, MERTK, IFNγ, and IL18R1) that were differentially expressed in COVID-19 patients in all five studies. Except CCL16, which was higher in controls, all proteins were overexpressed in COVID-19 patients. Pathway analysis revealed concordant trends across all studies with pathways related to cytokine-cytokine interaction, IL18 signaling, fluid shear stress and rheumatoid arthritis. Our results reaffirm previous findings related to a COVID-19 cytokine storm syndrome. Cross-study robustness of COVID-19 specific protein expression profiles support the utility of affinity proteomics as a tool and for the identification of potential therapeutic targets.