Differential protein expression of blood platelet components associated with adverse transfusion reactions

Abstract

Platelets found within platelet components (PCs) intended for transfusion release inflammatory molecules. Despite the implementation of leukoreduction, some of these PCs are occasionally associated with adverse transfusion reactions (ATRs). The aim of this study was to decipher the platelet proteome in two types of PCs, buffy-coat-derived pooled PCs (PPCs) and single-donor apheresis PCs (SDA-PCs), associated with ATRs. A label-free LC-MS/MS method was used for the proteomic analysis of washed platelet pellets from 3 PPCs and 3 SDA-PCs associated with ATRs, compared to matched controls. Bioinformatics tools allowed us to characterise the differentially expressed (DE) proteins between cases (ATR-PCs) and controls (no.ATR-PCs). From the PPCs and SDA-PCs, 473 and 146 proteins were DE, respectively. The functional interpretation of these proteins revealed enrichment in platelet activation and degranulation as the most important biological process. The most dysregulated pathways were integrin signaling for PPCs and acute phase response signaling for SDA-PCs. Interestingly, inflammatory disorders were found to be enriched in both PC types. Profound proteome changes were found in the platelets of PCs that led to clinical ATRs in patients. This study presents the first exploration of the platelet proteomic signature associated with ATRs and could provide clues to improving transfusion medicine. BIOLOGICAL SIGNIFICANCE: Adverse transfusion reactions (ATRs) can still occur after transfusion of platelet components (PC). This is the first report on the proteomic analysis of PCs associated with ATR. In this study, the contents of PC bags implicated in ATRs were examined. The aims of this study were to characterise molecules that could be central to the inflammation of ATRs and to highlight dysregulated mechanisms to explain the onset of ATRs. Two types of PCs were used: 3 PPCs (each from 5 donors) and 3 SDA-PCs (each from one donor). We have shown that the two types of PCs, from bags undergoing different processing (i.e., sampling, preparation), involve two types of dysregulated - pathophysiological mechanisms associated with the onset of ATRs. The most dysregulated signaling pathways were cytoskeleton and integrin regulation for PPCs, acute phase response signaling and remodelling of adherens junctions for SDA-PCs. Inflammation, platelet activation and degranulation processes were present in both PC types but were more important for PPCs. This proteomics analysis provides a better understanding of the pathophysiological mechanisms involved in ATRs and may lead to novel steps to ensure safe PC transfusion.

Keywords: Adverse transfusion reaction; Bioinformatic analysis; Dysregulated mechanisms; Inflammatory disorders; Platelet proteome; Untargeted label-free method.