Platelet concentrates (PCs) are prepared at blood banks for transfusion to patients in certain clinical conditions associated with a low platelet count. To prevent
transfusion-transmitted infections via PCs, different pathogen reduction (PR) systems have been developed that inactivate the
nucleic acids of contaminating pathogens by chemical cross-linking, a mechanism that may also affect platelets'
nucleic acids. We previously reported that treatment of stored platelets with the PR system Intercept significantly reduced the level of half of the
microRNAs that were monitored, induced platelet activation and compromised the platelet response to physiological agonists. Using genome-wide differential expression (DE)
RNA sequencing (
RNA-Seq), we now report that Intercept markedly perturbs the
mRNA transcriptome of human platelets and alters the expression level of >800 mRNAs (P<0.05) compared to other PR systems and control platelets. Of these, 400 genes were deregulated with DE corresponding to fold changes (FC) ≥ 2. At the p-value < 0.001, as many as 147 genes were deregulated by ≥ 2-fold in Intercept-treated platelets, compared to none in the other groups. Finally, integrated analysis combining expression data for
microRNA (
miRNA) and
mRNA, and involving prediction of
miRNA-
mRNA interactions, disclosed several positive and inverse correlations between
miRNAs and mRNAs in stored platelets. In conclusion, this study demonstrates that Intercept markedly deregulates the platelet
mRNA transcriptome, concomitant with reduced levels of
mRNA-regulatory
miRNAs. These findings should enlighten authorities worldwide when considering the implementation of PR systems, that target
nucleic acids and are not specific to pathogens, for the management of blood products.