Cell-free nucleic acids are present in blood products and regulate genes of innate immune response.

BACKGROUND: Extracellular nucleic acids circulate in plasma. They are expected to be present in manufactured blood products eligible for transfusion, but little is known about their biological activity on human cells. The aim of this study is to investigate whether cell-free nucleic acids (CFNAs) are present and biologically active in red blood cell units (RBCUs), fresh frozen plasmas, and platelet concentrates. STUDY DESIGN AND METHODS: CFNAs were extracted from RBCUs, fresh frozen plasma, and platelet concentrates. Their nature and structure were analyzed by regular methods of nucleic acid detection/quantification. A normalized polymerase chain reaction combining amplification of a CFNA marker (Alu 115) and amplification of an internal nonhuman DNA control spiked in all samples (phiX 174) was developed to study CFNA release after RBCU storage. The impact of CFNAs on gene regulation was tested by microarray after coculture with peripheral blood mononuclear cells and macrophages. RESULTS: Extracellular double-stranded DNA was present in all blood products, with higher amounts found in cellular suspensions (RBCUs and platelet concentrates). Storage up to 40 days did not influence release from RBCUs, and CFNA amount varied considerably from one unit to another. Microarray experiments showed that exposition of macrophages to CFNA increased the expression of genes involved in the innate immune response including chemokines, chemokine receptors, and receptors of the innate response. CONCLUSION: CFNAs are present in blood products. Immunoregulatory properties of CFNA are shown in vitro, providing new insights on biologically active components of blood products besides those for intended therapeutic use.

Metagenomics analysis of red blood cell and fresh-frozen plasma units.

BACKGROUND: Although the risk of transmitting infectious agents by blood transfusion is dramatically reduced after donor selection, leukoreduction, and laboratory testing, some could still be present in donor's blood. A description of metagenomes in blood products eligible for transfusion represents relevant information to evaluate the risk of pathogen transmission by transfusion. STUDY DESIGN AND METHODS: Detection of viruses, bacteria, and fungi genomes was made by high-throughput sequencing (HTS) of 600 manufactured blood products eligible for transfusion: 300 red blood cell (RBC) and 300 fresh-frozen plasma (FFP) units. RESULTS: Anelloviruses and human pegivirus, frequent in the blood of healthy individuals, were found. Human papillomavirus type 27 and Merkel cell polyomavirus, present on the skin, were also detected. Unexpectedly, astrovirus MLB2 was identified and characterized in a FFP unit. The presence of astrovirus MLB2 was confirmed in donor's blood and corresponded to an asymptomatic acute viremia. Sequences of bacteria and fungi were also detected; they are likely the result of environmental contamination. CONCLUSION: This study demonstrates that HTS is a promising tool for detecting common and less frequent infectious pathogens in blood products.