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    Poster Networking

    Vascular Biology

    Poster Networking Session

    PB1427 - Reduced ADAMTS13 activity in Staphylococcus aureus bacteremia is associated with neutrophil-mediated citrullination

    Tuesday, June 27, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Presenting Author(s)

    • Caroline P. Martens, MD (she/her/hers)

      PhD candidate
      KU Leuven
      Leuven, Vlaams-Brabant, Belgium

      • Co-Author(s)

    • MP

      Marijke Peetermans

      MD PhD
      Medical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
      Leuven, Vlaams-Brabant, Belgium

    • Marc Jacquemin, MD

      PhD
      Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
      Leuven, Vlaams-Brabant, Belgium

    • PV

      Peter Verhamme, MD, PhD

      MD, PhD
      University Hospitals Leuven, Belgium
      Leuven, Vlaams-Brabant, Belgium

    • Kimberly Martinod, PhD

      Assistant Professor
      Center of Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
      Leuven, Vlaams-Brabant, Belgium

    Background: In patients with Staphylococcus aureus bacteremia, we previously reported decreased ADAMTS13 activity early after bacteremia onset and high levels of neutrophil extracellular traps (NETs), von Willebrand factor (VWF) and peptidylarginine deiminase 4 (PAD4) throughout the disease course. PAD4 citrullinates and thus inactivates ADAMTS13 but whether this occurs in the context of systemic infection and could be related to neutrophil activation and the release of NETs or bacterial sources of PADs remains unknown.

    Aims: To obtain clinical evidence of the longitudinal evolution of ADAMTS13 activity in systemic infection and to investigate the potential source of PAD4 inactivating ADAMTS13 in plasma.

    Methods: Plasma samples from hospitalized patients with Staphylococcus aureus bacteremia were collected within 36 hours after bacteremia onset and at day 1, 4 and between day 7-10 after enrollment. Samples were analyzed for ADAMTS13 activity and Spearman correlation analyses were performed with NETs, VWF, PAD4 and clinical parameters. Additionally, recombinant human PAD4 and S. aureus were assessed in vitro for their potential to modulate ADAMTS13 activity in plasma.

    Results: Plasma ADAMTS13 activity is decreased early after bacteremia onset and partially recovers as patients show clinical recovery. In contrast, PAD4 levels remain high. ADAMTS13 activity and PAD4 levels are negatively correlated throughout the disease course. PAD4 antigen levels are positively correlated with NET biomarkers in the early disease phase, while ADAMTS13 activity remains negatively correlated with NET biomarkers throughout the disease course. In vitro, recombinant PAD4 but not S. aureus itself is able to reduce ADAMTS13 activity in normal human plasma.

    Conclusion(s): Levels of PAD4 correlate with reduced ADAMTS13 activity, with neutrophils as the likely source of PAD activity in patients with S. aureus bacteremia.