Diagnostic accuracy of neutrophil-derived circulating free DNA (cf-DNA/NETs) for septic arthritis.
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.
Department of Trauma and Hand Surgery, University Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany. tim.loegters@uni-duesseldorf.de
Tim
T
Lögters
Adnana
A
Paunel-Görgülü
Christoph
C
Zilkens
Jens
J
Altrichter
Martin
M
Scholz
Simon
S
Thelen
Rüdiger
R
Krauspe
Stefan
S
Margraf
Teresa
T
Jeri
Joachim
J
Windolf
Marcus
M
Jäger
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001170:Arthritis, Infectious / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D004247:DNA; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D011379:Prognosis; D012372:ROC Curve; D013582:Synovial Fluid / Q000737:chemistry
D015415:Biomarkers; D004269:DNA, Bacterial; D015850:Interleukin-6; D002097:C-Reactive Protein; D004247:DNA