Cell-Free DNA in Plasma and Serum Indicates Disease Severity and Prognosis in Blunt Trauma Patients

Abstract

Background: Trauma is still a major cause of mortality in people < 50 years of age. Biomarkers are needed to estimate the severity of the condition and the patient outcome. Methods: Cell-free DNA (cfDNA) and further laboratory markers were determined in plasma and serum of 164 patients at time of admission to the emergency room. Among them were 64 patients with severe trauma (Injury Severity Score (ISS) ≥ 16), 51 patients with moderate trauma (ISS < 16) and 49 patients with single fractures (24 femur neck and 25 ankle fractures). Disease severity was objectified by ISS and Glasgow Coma Scale (GCS). Results: cfDNA levels in plasma and serum were significantly higher in patients with severe multiple trauma (SMT) than in those with moderate trauma (p = 0.002, p = 0.003, respectively) or with single fractures (each p < 0.001). CfDNA in plasma and serum correlated very strongly with each other (R = 0.91; p < 0.001). The AUC in ROC curves for identification of SMT patients was 0.76 and 0.74 for cfDNA in plasma and serum, respectively—this was further increased to 0.84 by the combination of cfDNA and hemoglobin. Within the group of multiple trauma patients, cfDNA levels were significantly higher in more severely injured patients and patients with severe traumatic brain injury (GCS ≤ 8 versus GCS > 8). Thirteen (20.3%) of the multiple trauma patients died during the first week after trauma. Levels of cfDNA were significantly higher in non-surviving patients than in survivors (p < 0.001), reaching an AUC of 0.81 for cfDNA in both, plasma and serum, which was further increased by the combination with hemoglobin and leukocytes. Conclusions: cfDNA is valuable for estimation of trauma severity and prognosis of trauma patients.

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies

“…All these pathologies could theoretically be driven – partly or completely – by immunogenic self-DNA and in fact, all of them have been related to self-DNA in the context of non-COVID-19 pathologies. Using trauma as an example, several prospective observational studies reported elevated concentrations of free cfDNA ( 66 – 68 , 70 ), or of histone-complexed cfDNA ( 170 ), in the blood of severely injured trauma patients. In all these studies, the cfDNA concentrations correlated with poor clinical outcome ( 66 – 68 , 70 , 170 ).…”

“…Using trauma as an example, several prospective observational studies reported elevated concentrations of free cfDNA ( 66 – 68 , 70 ), or of histone-complexed cfDNA ( 170 ), in the blood of severely injured trauma patients. In all these studies, the cfDNA concentrations correlated with poor clinical outcome ( 66 – 68 , 70 , 170 ). The causal role cfDNA in the inflammatory response to trauma was shown by the group of Carl Hauser at Harvard ( 67 , 69 ).…”

“…However, DAMPs-mediated signalling can also generate detrimental effects, particularly when a massive release of pro-inflammatory DAMPs from dying cells causes more cells to die: a situation that strongly contributes to the CD4+ T cell depletion in patients infected with HIV-1 ( 63 , 64 ), reviewed in ( 65 ). Extracellular self-DNA has been associated with multiorgan failure after severe trauma ( 66 – 70 ), including sepsis-like systemic inflammation ( 71 ), sepsis ( 72 ), can lead to myocarditis ( 73 – 76 ) or lung inflammation ( 77 ), facilitates the reactivation of latent virus infections, including Herpes Simplex Virus, Varicella Zoster Virus, or HIV-1, and favours the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and psoriasis ( 67 , 76 , 78 – 86 ). Elevated plasma levels of cf nDNA or mtDNA are common in HIV-1-infected patients ( 87 – 91 ) and might explain the chronic inflammatory and autoimmune-related pathologies that frequently develop in this group ( 65 , 92 – 94 ): examples include thrombocytopenia ( 95 – 98 ), diverse forms of vasculitis ( 99 , 100 ), myocarditis ( 101 ), psoriasis ( 102 – 104 ), rheumatoid arthritis ( 105 , 106 ), SLE ( 102 , 105 , 106 ) and herpes zoster ( 107 ).…”

Comparative Analysis of Nucleic Acid-Binding Polymers as Potential Anti-Inflammatory Nanocarriers

“…NABNs are nanomaterials that recognize danger- and pathogen-associated molecular patterns (DAMPs and PAMPs) that stimulate TLRs, leading to inflammation in chronic disease [ 4 , 5 , 6 ]. DAMPs and PAMPs have been clinically found to be increased in trauma [ 7 , 8 , 9 ], inflammatory disease [ 10 , 11 , 12 , 13 ], and cancer [ 14 , 15 , 16 ]. Cell-free nucleic acids are being used for early disease detection, and high levels of DAMPs and PAMPs have been correlated to lower prognoses in many disease states [ 7 , 12 , 13 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

“…DAMPs and PAMPs have been clinically found to be increased in trauma [ 7 , 8 , 9 ], inflammatory disease [ 10 , 11 , 12 , 13 ], and cancer [ 14 , 15 , 16 ]. Cell-free nucleic acids are being used for early disease detection, and high levels of DAMPs and PAMPs have been correlated to lower prognoses in many disease states [ 7 , 12 , 13 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. NABNs can reduce TLR overactivation by acting as molecular scavengers that bind nucleic acids and other charged molecules, including DAMPs and PAMPs [ 25 ].…”