Plasma DNA as a Prognostic Marker in Trauma Patients

Abstract

Background: Recently, much interest has developed in the potential use of plasma DNA as a diagnostic and monitoring tool. We hypothesized that plasma DNA is increased in patients with trauma and may be prognostic in such patients. Methods: We studied 84 patients who had sustained an acute blunt traumatic injury. We measured plasma DNA by a real-time quantitative PCR assay for the β-globin gene. Blood samples were collected at a median time of 60 min following injury. Blood samples were also obtained from 27 control subjects. Results: The median plasma DNA concentrations in the control, minor/moderate trauma (Injury Severity Score <16; n = 47), and major trauma (Injury Severity Score ≥16; n = 37) groups were 3154 kilogenome-equivalents/L, 13 818 kilogenome-equivalents/L, and 181 303 kilogenome-equivalents/L, respectively. Plasma DNA concentrations in patients with adverse outcomes, including acute lung injury, acute respiratory distress syndrome, and death, had 11.6- to 12-fold higher plasma DNA concentrations than those who did not develop these complications. At a cutoff of 232 719 kilogenome-equivalents/L, the sensitivities of plasma DNA analysis for the prediction of acute lung injury, acute respiratory distress syndrome, and death were 100% (95% confidence interval, 100–100%), 100% (95% confidence interval, 100–100%), and 78% (95% confidence interval, 40–97%), respectively. The respective specificities were 81% (95% confidence interval, 71–89%), 80% (95% confidence interval, 70–88%), and 82% (95% confidence interval, 71–90%). Conclusions: Plasma DNA is increased after trauma and may be a potentially valuable prognostic marker for these patients.

Expression and function of Toll-like receptor 9 in severely injured patients prone to sepsis

“…Moreover, also self-DNA is recognized by TLR9 in an experimental model [12]. Significant increases in circulating DNA in the plasma of trauma patients have been reported [27], and DNA drives autoimmunity [11]. Therefore, we analysed anti-DNA antibodies in trauma patients with and without sepsis during 14 days after trauma and found no difference between these two groups; moreover, all values were in the normal range (unpublished results).…”

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

“…For example, ctDNA molecules from urine and plasma samples vary in their fragment lengths with shorter fragments appearing in urine where more DNAses are abundant than in blood. 30 However, the exact proportion of each process contributing to the total cfDNA pool remains unknown, and the release of DNA is further influenced by physiological processes and disorders, including pregnancy, 31 exhaustive exercise, 32,33 trauma, 34,35 inflammation, 36 myocardial infarction, 37 autoimmune disorders, 38 and acute stroke. 39,40 While in healthy individuals regular apoptotic cell death of lymphoid and myeloid cells as part of hematopoietic homeostasis constitutes the majority of cfDNA, 29,41 the contribution of tumor-derived ctDNA in the blood of cancer patients varies substantially from <0.01% to more than 60% of alleles in the circulation.…”

Circulating (cell‐free) nucleic acids – A promising, non‐invasive tool for early detection of several human diseases

“…The occurrence of CNA gained the interest of a wider scientific community investigating other pathological diseases like stroke, autoimmune disorders, myocardial infraction (MI), diabetes, trauma and even prion diseases. Lo's group established a direct relationship between tissue injury in acute trauma and elevated plasma DNA levels [21]. Similarly, release of DNA into the peripheral blood can take place in acute stroke which involves CNS tissue damage.…”