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Dysregulated pathways and differentially expressed proteins associated with adverse transfusion reactions in different types of platelet components.
Journal of Proteomics ( IF 2.8 ) Pub Date : 2020-02-20 , DOI: 10.1016/j.jprot.2020.103717 Chaker Aloui 1 , Céline Barlier 2 , Danielle Awounou 2 , Saliou Thiam 2 , Jocelyne Fagan 1 , Stéphane Claverol 3 , Emmanuelle Tavernier 4 , Christiane Mounier 4 , Hind Hamzeh-Cognasse 5 , Fabrice Cognasse 1 , Olivier Garraud 6 , Sandrine Laradi 1
Journal of Proteomics ( IF 2.8 ) Pub Date : 2020-02-20 , DOI: 10.1016/j.jprot.2020.103717 Chaker Aloui 1 , Céline Barlier 2 , Danielle Awounou 2 , Saliou Thiam 2 , Jocelyne Fagan 1 , Stéphane Claverol 3 , Emmanuelle Tavernier 4 , Christiane Mounier 4 , Hind Hamzeh-Cognasse 5 , Fabrice Cognasse 1 , Olivier Garraud 6 , Sandrine Laradi 1
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Platelet components (PCs) are occasionally associated with adverse transfusion reactions (ATRs). ATRs can occur regardless of the type of PC being transfused, whether it is a single-donor apheresis PC (SDA-PC) or a pooled PC (PPCs). The purpose of this study was to investigate the proteins and dysregulated pathways in both of the main types of PCs. The proteomic profiles of platelet pellets from SDA-PCs and PPCs involved in ATRs were analysed using the label-free LC-MS/MS method. Differentially expressed proteins with fold changes >|1.5| in clinical cases versus controls were characterised using bioinformatic tools (RStudio, GeneCodis3, and Ingenuity Pathways Analysis (IPA). The proteins were confirmed by western blotting. The common primary proteins found to be dysregulated in both types of PCs were the mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20), multimerin-1 (MMRN1), and calumenin (CALU), which are associated with the important enrichment of platelet activation, platelet degranulation, and mitochondrial activity. Furthermore, this analysis revealed the involvement of commonly dysregulated canonical pathways, particularly mitochondrial dysfunction, platelet activation, and acute phase response. This proteomic analysis provided an interesting contribution to our understanding of the meticulous physiopathology of PCs associated with ATR. A larger investigation would assist in delineating the most relevant proteins to target within preventive transfusion safety strategies. BIOLOGICAL SIGNIFICANCE: Within platelet transfusion strategies, the two primary types of PCs predominantly processed in Europe, include (i) single donor apheresis PCs (SDA-PCs) from one donor and (ii) pooled PCs (PPCs). The current study used PCs from five buffy coats derived from five whole blood donations that were identical in ABO, RH1 and KEL1 groups. Both PC types were shown to be associated with the onset of an ATR in the transfused patient. Several common platelet proteins were found to be dysregulated in bags associated with ATR occurrences regardless of the type of PCs transfused and of their process. The dysregulated proteins included mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20), which is involved in a fatty acid oxidation disorder; calumenin (CALU); and multimerin-1 (MMRN1), which is chiefly involved in platelet activation and degranulation. Dysregulated platelet protein pathways for ATRs that occurred with SDA-PCs and PPCs could support the dysregulated functions found in association with those three proteins. Those common platelet proteins may become candidates to define biomarkers associated with the onset of an ATR from PC transfusions, including monitoring during the quality steps of PC manufacturing, provided that the results are confirmed in larger cohorts. This study enriches our knowledge of platelet proteomics in PCs under pathological conditions.
中文翻译：
在不同类型的血小板组分中与不良输血反应相关的失调的途径和差异表达的蛋白质。
血小板成分（PC）有时与不良的输血反应（ATR）相关。无论输注的PC是哪种类型，无论是单供血单采单采PC（SDA-PC）还是合并PC（PPC），都可以发生ATR。这项研究的目的是调查两种主要类型PC中的蛋白质和失调的途径。使用无标记LC-MS / MS方法分析了参与ATR的SDA-PC和PPC的血小板沉淀的蛋白质组学特征。倍数变化差异表达的蛋白质> | 1.5 | 使用生物信息学工具（RStudio，GeneCodis3和Ingenuity Pathways Analysis（IPA））对临床病例与对照组进行了特征鉴定，并通过Western印迹法确认了蛋白质。在这两种类型的PC中发现失调的常见主要蛋白质是线粒体肉碱/酰基肉碱载体蛋白（SLC25A20），multimerin-1（MMRN1）和calumenin（CALU），它们与血小板活化，血小板的重要富集有关脱粒和线粒体活性。此外，该分析揭示了通常失调的规范途径的参与，特别是线粒体功能障碍，血小板活化和急性期反应。蛋白质组学分析为我们对与ATR相关的PC的细致生理病理学的理解提供了有趣的贡献。更大的研究将有助于在预防性输血安全策略中确定最相关的蛋白质作为目标。生物学意义：在血小板输注策略中，在欧洲主要处理的两种主要类型的PC，包括（i）来自一个捐赠者的单捐赠者单采单采PC（SDA-PC）和（ii）合并的PC（PPC）。当前的研究使用了来自五次血沉棕黄层的PC，这些血沉棕黄层来自五次全血捐赠，在ABO，RH1和KEL1组中是相同的。在输血患者中，两种PC类型均与ATR的发作有关。发现与输血相关的袋子中有几种常见的血小板蛋白失调，而与输血的PC类型及其过程无关。失调的蛋白质包括线粒体肉碱/酰基肉碱载体蛋白（SLC25A20），它与脂肪酸氧化失调有关。calumenin（CALU）; multimerin-1（MMRN1），主要参与血小板活化和脱粒。SDA-PCs和PPCs发生的ATRs血小板蛋白通路异常可能支持与这三种蛋白相关的功能失调。如果在较大的队列研究中证实了这些常见的血小板蛋白，它们可能会成为定义与PC输血ATR发作相关的生物标志物的候选物，包括在PC制造质量步骤中进行监测。这项研究丰富了我们在病理条件下PC中血小板蛋白质组学的知识。只要结果在更大的队列中得到证实 这项研究丰富了我们在病理条件下PC中血小板蛋白质组学的知识。只要结果在更大的队列中得到证实 这项研究丰富了我们在病理条件下PC中血小板蛋白质组学的知识。
更新日期：2020-02-20
中文翻译：
在不同类型的血小板组分中与不良输血反应相关的失调的途径和差异表达的蛋白质。
血小板成分（PC）有时与不良的输血反应（ATR）相关。无论输注的PC是哪种类型，无论是单供血单采单采PC（SDA-PC）还是合并PC（PPC），都可以发生ATR。这项研究的目的是调查两种主要类型PC中的蛋白质和失调的途径。使用无标记LC-MS / MS方法分析了参与ATR的SDA-PC和PPC的血小板沉淀的蛋白质组学特征。倍数变化差异表达的蛋白质> | 1.5 | 使用生物信息学工具（RStudio，GeneCodis3和Ingenuity Pathways Analysis（IPA））对临床病例与对照组进行了特征鉴定，并通过Western印迹法确认了蛋白质。在这两种类型的PC中发现失调的常见主要蛋白质是线粒体肉碱/酰基肉碱载体蛋白（SLC25A20），multimerin-1（MMRN1）和calumenin（CALU），它们与血小板活化，血小板的重要富集有关脱粒和线粒体活性。此外，该分析揭示了通常失调的规范途径的参与，特别是线粒体功能障碍，血小板活化和急性期反应。蛋白质组学分析为我们对与ATR相关的PC的细致生理病理学的理解提供了有趣的贡献。更大的研究将有助于在预防性输血安全策略中确定最相关的蛋白质作为目标。生物学意义：在血小板输注策略中，在欧洲主要处理的两种主要类型的PC，包括（i）来自一个捐赠者的单捐赠者单采单采PC（SDA-PC）和（ii）合并的PC（PPC）。当前的研究使用了来自五次血沉棕黄层的PC，这些血沉棕黄层来自五次全血捐赠，在ABO，RH1和KEL1组中是相同的。在输血患者中，两种PC类型均与ATR的发作有关。发现与输血相关的袋子中有几种常见的血小板蛋白失调，而与输血的PC类型及其过程无关。失调的蛋白质包括线粒体肉碱/酰基肉碱载体蛋白（SLC25A20），它与脂肪酸氧化失调有关。calumenin（CALU）; multimerin-1（MMRN1），主要参与血小板活化和脱粒。SDA-PCs和PPCs发生的ATRs血小板蛋白通路异常可能支持与这三种蛋白相关的功能失调。如果在较大的队列研究中证实了这些常见的血小板蛋白，它们可能会成为定义与PC输血ATR发作相关的生物标志物的候选物，包括在PC制造质量步骤中进行监测。这项研究丰富了我们在病理条件下PC中血小板蛋白质组学的知识。只要结果在更大的队列中得到证实 这项研究丰富了我们在病理条件下PC中血小板蛋白质组学的知识。只要结果在更大的队列中得到证实 这项研究丰富了我们在病理条件下PC中血小板蛋白质组学的知识。
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