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 +/- 386 ng/ml, n = 9) were significantly increased compared to patients with noninfectious joint inflammation (1,040 +/- 208 ng/ml, n = 17) or osteoarthritis (278 +/- 34 ng/ml, n = 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.

• Authors: Tim Lögters, Adnana Paunel-Görgülü, Christoph Zilkens, Jens Altrichter, Martin Scholz, Simon Thelen, Rüdiger Krauspe, Stefan Margraf, Teresa Jeri, Joachim Windolf, Marcus Jäger
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 27 Issue 11 Pg. 1401-7 (Nov 2009) ISSN: 1554-527X [Electronic] United States
• PMID: 19422041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Chemical References

• Biomarkers
• DNA, Bacterial
• Interleukin-6
• C-Reactive Protein
• DNA

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Arthritis, Infectious (diagnosis, immunology)
• Biomarkers (blood)
• C-Reactive Protein (analysis)
• DNA
• DNA, Bacterial (analysis)
• Female
• Humans
• Interleukin-6 (analysis)
• Male
• Middle Aged
• Neutrophils (metabolism)
• Prognosis
• ROC Curve
• Synovial Fluid (chemistry)