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

Abramowski, Sophie Waldvogel; Tirefort, Diderik; Lau, Pierre; Guichebaron, Arthur; Taleb, Sofiane; Modoux, Christine; Chaduc, Coralie Lemoine; Cerdan, Pascale Bruyere; Lombard, P; Lecompte, Thomas; Preynat‐Seauve, Olivier

doi:10.1111/trf.14613

Cited by 15 publications

(18 citation statements)

References 43 publications

(68 reference statements)

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“…It has been demonstrated that the cell-free DNA content in red cell concentrates assessed by the Quant-iT PicoGreen assay is exceedingly low at around 1 ng/mL, (1) and via a different methodology, it has been shown that the DNA content of platelet concentrates and FFP is lower than that of red cell concentrates. (2) Furthermore, it has been established that preanalytical sampling errors, which are common in the clinical setting, may lead to spuriously high cell-free DNA levels, and these falsely elevated cell-free DNA levels would not be captured by a technically superior detection method. (3) In addition, we would like to emphasize that regardless of the origin of the cell-free DNA, elevated levels were associated with activation of coagulation, making it an interesting target for therapeutic strategies.…”

Section: To the Editormentioning

confidence: 99%

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Meijenfeldt

Lisman

2020

Liver Transpl

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Section: To the Editormentioning

confidence: 99%

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Meijenfeldt

Lisman

2020

Liver Transpl

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“…ecDNA comprises mainly nuclear DNA (nucDNA) and mitchondrial DNA (mitDNA). It is also present in the extracellular milieu of blood products (as shown in Table 1) [11][12][13][14][15][16][17][18][19][20]. However, a novel and significant role of ecDNA has emerged, involving its ability to trigger innate immune system responses and drive inflammation when released from mechanically injured cells [21].…”

Section: Introductionmentioning

confidence: 99%

Extracellular DNA in blood products and its potential effects on transfusion

Yang

et al. 2020

Bioscience Reports

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Blood transfusions are sometimes necessary after a high loss of blood due to injury or surgery. Some people need regular transfusions due to medical conditions such as haemophilia or cancer. Studies have suggested that extracellular DNA including mitochondrial DNA present in the extracellular milieu of transfused blood products has biological actions that are capable of activating the innate immune systems and potentially contribute to some adverse reactions in transfusion. From the present work, it becomes increasingly clear that extracellular DNA encompassed mitochondrial DNA is far from being biologically inert in blood products. It has been demonstrated to be present in eligible blood products and thus can be transfused to blood recipients. Although the presence of extracellular DNA in human plasma was initially detected in 1948, some aspects have not been fully elucidated. In this review, we summarize the potential origins, clearance mechanisms, relevant structures, and potential role of extracellular DNA in the innate immune responses and its relationship with individual adverse reactions in transfusion.

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“…In the case of blood products, the following criteria must be carefully considered when choosing the extraction method: (i) due to a leukocyte reduction prior to manufacturing, total nucleic acids are present at very low concentrations. As a case in point, we observed in FFP a dsDNA concentration ranging from 2.8 ± 0.9 ng/mL [27]; (ii) RBCU contain mainly conservation buffer and erythrocytes (hemoglobin); (iii) PC mainly contain residual plasma, conservation buffer and platelets. From our experience, methods designed for the isolation of cell-free nucleic acid from all three types of blood products showed good yields [27].…”

Section: Technical Aspects Of Ngs Applied To Blood Products and Donormentioning

confidence: 99%

“…As a case in point, we observed in FFP a dsDNA concentration ranging from 2.8 ± 0.9 ng/mL [27]; (ii) RBCU contain mainly conservation buffer and erythrocytes (hemoglobin); (iii) PC mainly contain residual plasma, conservation buffer and platelets. From our experience, methods designed for the isolation of cell-free nucleic acid from all three types of blood products showed good yields [27]. …”

Section: Technical Aspects Of Ngs Applied To Blood Products and Donormentioning

confidence: 99%

“…These cell-free nucleic acids circulate in human plasma [25] and are mainly genomic dsDNA [25], but also contain small RNAs [26] and possibly viral DNA/RNA. Cell-free nucleic acids are described in RBCU, PC and FFP, showing in vitro an intrinsic capacity of innate immune response regulation [27]. Additive solutions are also present in blood products.…”

Section: Technical Aspects Of Ngs Applied To Blood Products and Donormentioning

confidence: 99%

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Viral Metagenomics of Blood Donors and Blood-Derived Products Using Next-Generation Sequencing

Waldvogel-Abramowski

Taleb

Alessandrini

et al. 2019

Transfus Med Hemother

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Transfusion-transmitted infections remain a permanent threat in medicine. It keeps the burden of the past, marked by serious infections transmitted by transfusion, and is constantly threatened by emerging viruses. The global rise of immunosuppression among patients undergoing frequent transfusions exacerbates this problem. Over the past decade, criteria for donor selection have become increasingly more stringent. Although routine nucleic acid testing (NAT) for virus-specific detection has become more sensitive, these safety measures are only valuable for a limited number of select viruses. The scientific approach to this is however changing, with the goal of trying to identify infectious agents in donor units as early as possible to mitigate the risk of a clinically relevant infection. To this end, and in addition to an epidemiological surveillance of the general population, researchers are adopting new methods to discover emerging infectious agents, while simultaneously screening for an extended number of viruses in donors. Next-generation sequencing (NGS) offers the opportunity to explore the entire viral landscape in blood donors, the so-called metagenomics, to investigate severe transfusion reactions of unknown etiology. In the not too distant future, one could imagine this platform being used for routine testing of donated blood products.

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

Abstract: 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.

Cited by 15 publications

References 43 publications

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Extracellular DNA in blood products and its potential effects on transfusion

Viral Metagenomics of Blood Donors and Blood-Derived Products Using Next-Generation Sequencing

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