Detection of Circulating DNA in Plasma of Patients with Pulmonary Embolism by Counterimmunoelectrophoresis

Riboldi, Piersandro; Asero, Riccardo; Marazzini, L; Longhini, E; Cherubini, P.; Pacetti, Miriam; Invernizzi, Federica

doi:10.1159/000194596

Cited by 8 publications

(4 citation statements)

References 8 publications

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“…Prior studies investigating the role of NETs in clinical VTE diagnostics have employed surrogate NET markers, such as cfDNA, nucleosomes and MPO [21,23]. There are five studies showing elevations of cfDNA in PE patients [30][31][32][33][34] and three studies showing no elevations in this patient population [35][36][37]. More recently, granular proteins have been examined as potential diagnostic markers in DVT patients.…”

Section: Discussionmentioning

confidence: 99%

Markers of neutrophil activation and neutrophil extracellular traps in diagnosing patients with acute venous thromboembolism: A feasibility study based on two VTE cohorts

et al. 2022

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Background Venous thromboembolism (VTE) diagnosis would greatly benefit from the identification of novel biomarkers to complement D-dimer, a marker limited by low specificity. Neutrophil extracellular traps (NETs) have been shown to promote thrombosis and could hypothetically be used for diagnosis of acute VTE. Objectives To assess the levels of specific markers of neutrophil activation and NETs and compare their diagnostic accuracy to D-dimer. Methods We measured plasma levels of neutrophil activation marker neutrophil elastase (NE), the NET marker nucleosomal citrullinated histone H3 (H3Cit-DNA) and cell-free DNA in patients (n = 294) with suspected VTE (pulmonary embolism and deep vein thrombosis) as well as healthy controls (n = 30). A total of 112 VTE positive and 182 VTE negative patients from two prospective cohort studies were included. Results Higher levels of H3Cit-DNA and NE, but not cell-free DNA, were associated with VTE. Area under receiver operating curves (AUC) were 0.90 and 0.93 for D-dimer, 0.65 and 0.68 for NE and 0.60 and 0.67 for H3Cit-DNA in the respective cohorts. Adding NE and H3Cit-DNA to a D-dimer based risk model did not improve AUC. Conclusions Our study demonstrates the presence of neutrophil activation and NET formation in VTE using specific markers. However, the addition of NE or H3Cit-DNA to D-dimer did not improve the discrimination compared to D-dimer alone. This study provides information on the feasibility of using markers of NETs as diagnostic tools in acute VTE. Based on our findings, we believe the potential of these markers are limited in this setting.

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Section: Discussionmentioning

confidence: 99%

Markers of neutrophil activation and neutrophil extracellular traps in diagnosing patients with acute venous thromboembolism: A feasibility study based on two VTE cohorts

et al. 2022

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“…Serum or plasma samples have been widely used to characterize the concentration of cell‐free genomic DNA or viral nucleic acid as a way to monitor various diseases, including malignancy, 3–9 SLE, 1 pulmonary embolism, 2 and viral infections, 21–24 and to study fetomaternal chimerism 11,12 . Many studies investigating cell‐free DNA in blood treat plasma and serum as interchangeable sources of DNA.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, it has been reported that plasma DNA was significantly higher in patients with SLE (59.7%) than in normal controls (7.4%) 1 . Furthermore, 15 (94%) of 16 patients with pulmonary embolism were found to have increased levels of free plasma DNA, whereas all normal subjects tested negative for free plasma DNA 2 . Various malignancies have also been associated with high concentrations of cell‐free DNA in both plasma and serum 3–9 ; as compared to levels in healthy controls, plasma DNA levels have been reported as significantly higher in persons with cancers of the lung, pancreas, head and neck, breast, ovary, and uterus 5–8 …”

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confidence: 98%

Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma

et al. 2001

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Most cell-free DNA in serum samples is generated during the process of clotting in the original collection tube. The concentration of cell-free genomic DNA in fresh plasma is probably the same as that in circulation. Consequently, while serum samples should not be used to monitor the concentration of cell-free DNA in a patient's circulation, serum collected from sample tubes containing clots (i.e., without anticoagulant), 3 to 5 days after the date of phlebotomy, could be useful as a source of DNA with which to screen for posttransfusion microchimerism.

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“…Several subsequent studies analyzed ceDNA in PE patients with controversial results. [50][51][52][53][54][55][56][57][58] Four studies identified ceDNA in more than 80% of patients diagnosed with PE using lung scans, [50][51][52][53] while three independent studies detected ceDNA in less than 20% of patients diagnosed with PE using pulmonary angiography. [55][56][57][58] These discrepancies can be explained by differences in diagnostic criteria of PE and differences in anti-DNA antibodies used in CIE. 57 Recently, nuclear-and mitochondrial-specific DNA sequences were analyzed by quantitative polymerized chain reaction (qPCR) in plasma from PE patients diagnosed with computed tomographic pulmonary angiography.…”

Section: Venous Thromboembolismmentioning

confidence: 99%

Circulating Extracellular DNA: Cause or Consequence of Thrombosis?

Jiménez-Alcázar

Kim

Fuchs

2017

Semin Thromb Hemost

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Thrombosis leads to ischemic organ damage in cardiovascular and thromboembolic diseases. Neutrophils promote thrombosis in vitro and in vivo by releasing neutrophil extracellular traps (NETs). NETs are composed of DNA filaments coated with histones and neutrophil enzymes such as myeloperoxidase (MPO). Circulating extracellular DNA (ceDNA) is widely used as a surrogate marker to monitor NET formation in thrombosis. This narrative review summarizes the association of ceDNA with human thrombosis. Levels of ceDNA indicate the extent and outcome of several cardiovascular and thromboembolic diseases, including myocardial infarction, stroke, and venous thromboembolism. ceDNA correlates with markers of coagulation and platelet consumption, thus supporting the hypothesis that ceDNA may be a surrogate marker of thrombus formation. In addition, ceDNA levels correlate with markers of cell injury and size of ischemic lesions, suggesting that ceDNA does not derive from NETs but is probably released from damaged organs. Few studies identified NET-specific biomarkers such as DNA-MPO complexes in the blood of patients with thrombosis. In conclusion, it remains to be established whether ceDNA in patients derives from NETs and is a cause or consequence of thrombosis.

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Detection of Circulating DNA in Plasma of Patients with Pulmonary Embolism by Counterimmunoelectrophoresis

Cited by 8 publications

References 8 publications

Markers of neutrophil activation and neutrophil extracellular traps in diagnosing patients with acute venous thromboembolism: A feasibility study based on two VTE cohorts

Markers of neutrophil activation and neutrophil extracellular traps in diagnosing patients with acute venous thromboembolism: A feasibility study based on two VTE cohorts

Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma

Circulating Extracellular DNA: Cause or Consequence of Thrombosis?

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