PB0743 - Cell-free DNA is increased in plasma of immunothrombotically dysregulated patients with periprosthetic joint infection in part due to lower DNaseI activity

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Raquel Herranz, MSc

PhD Candidate
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Co-Author(s)

Julia Oto

Postdoctoral Researcher
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
MF

Manuel Fuertes

Medical doctor
Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
EP

Emma Plana

Postdoctoral Researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Angiology and Vascular Surgery Service, La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
FC

Fernando Cana

Laboratory Technician
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
CD

Carolina De la Calva

Medical doctor
Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
MA

Manuel Angulo

Medical Doctor
Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital
Valencia, Comunidad Valenciana, Spain
FA

Francisco Arguelles

Medical Doctor
Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital
Valencia, Comunidad Valenciana, Spain
JB

Jose Baeza

Medical Doctor
Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital
Valencia, Comunidad Valenciana, Spain
IB

Ignacio Baixauli

Medical doctor
Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
FB

Francisco Baixauli

Medical doctor
Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
JA

Jose Vicente Amaya

Medical doctor
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
PM

Pilar Medina

PI
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Background: Bacterial infection activates neutrophil activation through immunothrombosis. Neutrophils release neutrophil extracellular traps (NETs) in bacterial biofilm of periprosthetic joint infections (PJI). We previously evidenced an increase in NETs markers in PJI plasma and that plasma cell-free DNA (cfDNA) levels may improve PJI diagnosis. In some disorders like thrombotic microangiopathies, increased plasma cfDNA is mediated by impaired plasma DNaseI activity.

Aims: To ascertain whether increased plasma cfDNA in PJI patients may be mediated by lower DNaseI activity.

Methods: We obtained citrated plasma, in the preoperative period of prosthetic surgery, from 94 patients prospectively recruited. PJI was confirmed in 50 of these patients and 44 had no infection. cfDNA was quantified with PicoGreen (Life Technologies) and DNase I activity was measured with a single radial enzyme-diffusion (SRED) assay. The statistical analysis was performed with GraphPad (v.8.0.1).

Results: Plasma cfDNA levels were significantly higher in PJI patients (median 1403 ng/ml, 1st-3rd quartile: 1062-1617) compared to patients undergoing prosthetic surgery due to non-septic causes (920.5, 836.2-1361) (P < 0.0001). Interestingly, DNase I activity was significantly decreased in PJI (0.42 cm2, 0.38-0.51) than in non-PJI (0.55, 0.49-0.61) (P < 0.0001) (Figure 1).

Conclusion(s): The increase in plasma cfDNA in PJI patients may be due to a combination of increased NETosis and an impairment of DNaseI activity. Further in vitro studies are needed to clarify whether increased NETosis is beneficial or detrimental to fight PJI.
ISCIII-FEDER (PI17/00495, PI20/00075, FI21/00171), GVA (ACIF/2017/138), Zimmer Biomet and SETH.