Diagnostic accuracy of neutrophil‐derived circulating free DNA (cf‐DNA/NETs) for septic arthritis

Abstract

The release of ''neutrophil extracellular traps'' (NETs) has been identified as a novel immune response in innate immunity. NETs are composed of neutrophil-derived circulating free DNA (cf-DNA) and neutrophil cytoplasm-derived proteins such as proteases. In this study, we analyzed the putative diagnostic value of synovial cf-DNA/NETs for identification of septic arthritis. Forty-two patients with a joint effusion who had undergone arthrocentesis were included. From synovial fluid, cf-DNA/NETs (j-cf-DNA) levels were directly quantified. Diagnostic value of j-cf-DNA was compared with white blood cells (WBC), synovial white blood cells (j-WBC), C-reactive protein (CRP), j-IL-6, j-TNF alpha, j-IL-1 beta, and myeloperoxidase (j-MPO). Sensitivity, specificity, positive and negative predictive value, as well as ROC-curves for each parameter were calculated. Synovial fluid cf-DNA/NETs values from patients with septic arthritis (3,286 AE 386 ng/ ml, n ¼ 9) were significantly increased compared to patients with noninfectious joint inflammation (1,040 AE 208 ng/ml, n ¼ 17) or osteoarthritis (278 AE 34 ng/ml, n ¼ 16, p < 0.01). In conjunction with j-cf-DNA, j-IL-6 and j-IL-1 beta were significantly elevated (p < 0.01), but WBC, CRP, and j-WBC were not. At a cut-off of 300 ng/ml, j-cf-DNA had a sensitivity of 0.89, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.97. Receiver operation curves revealed largest areas under the curve for cf-DNA/NETs (0.933) and j-IL-6 (0.951). cf-DNA/NETs seem to be a valuable additional marker for the diagnosis of septic arthritis or periprosthetic infections. However, this result should be confirmed in a large clinical trial. ß

Experimental immunology Extracellular Traps: How to isolate and quantify extracellular DNA (ET-DNA)

“…The observation of Lögters et al [20] in septic arthritis correspond with this findings. Recently different studies started to highlight the role of NETs in different pathological conditions.…”

“…Always the short life-span of neutrophils should be taken into account. Activation can be performed by a multitude of reagents, including bacterial LPS, GM-CSF followed by TLR-4 or C5a [20]. The most frequently used reagent is PMA [12,14].…”

Mannheimia haemolytica and Its Leukotoxin Cause Macrophage Extracellular Trap Formation by Bovine Macrophages

“…Whether extracellular traps are beneficial or detrimental to host defense is unclear at this time. Although the potential beneficial effect of trapping and killing extracellular bacterial cells is obvious, the presence of NETs has recently been linked to several human disease states, including systemic lupus erythematosus (27), peritonitis (42,43), vasculitis (30), septic arthritis (31), and pre-eclampsia (25,26). What role macrophage extracellular traps play in host defense and the pathophysiology of infectious diseases will be the subject of future investigations.…”

Identification of neutrophil extracellular traps in the blood of patients with systemic inflammatory response syndrome

“…[7][8][9][10] Before the discovery of NETs, increases in circulating free DNA (cf-DNA) in the blood had been reported in various diseases including several cancers, [11][12][13] trauma, stroke, autoimmune disorders, sepsis and septic arthritis. [14][15][16] This cf-DNA was formerly thought to originate from necrotic and/or apoptotic cells, 17 but several articles have suggested an association between NETs and cf-DNA. [14][15][16][17][18] In these reports, cf-DNA was present both in infectious and noninfectious disease conditions, including a mouse model of lipopolysaccharide-induced shock.…”

“…[14][15][16] This cf-DNA was formerly thought to originate from necrotic and/or apoptotic cells, 17 but several articles have suggested an association between NETs and cf-DNA. [14][15][16][17][18] In these reports, cf-DNA was present both in infectious and noninfectious disease conditions, including a mouse model of lipopolysaccharide-induced shock. It was also reported that NETs in capillary vessels might be related to the pathophysiology of disseminated intravascular coagulation.…”