Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate w

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ORIGINAL PAPER

Serum citrullinated histone H3 concentrations differentiate patients with septic verses non‑septic shock and correlate with disease severity Yuzi Tian1,2 · Rachel M. Russo1 · Yongqing Li1   · Monita Karmakar1 · Baoling Liu1 · Michael A. Puskarich3,4 · Alan E. Jones5 · Kathleen A. Stringer6,7   · Theodore J. Standiford7 · Hasan B. Alam1 Received: 8 June 2020 / Accepted: 15 September 2020 © The Author(s) 2020

Abstract Purpose  Microbial infection stimulates neutrophil/macrophage/monocyte extracellular trap formation, which leads to the release of citrullinated histone H3 (CitH3) catalyzed by peptidylarginine deiminase (PAD) 2 and 4. Understanding these molecular mechanisms in the pathogenesis of septic shock will be an important next step for developing novel diagnostic and treatment modalities. We sought to determine the expression of CitH3 in patients with septic shock, and to correlate CitH3 levels with PAD2/PAD4 and clinically relevant outcomes. Methods  Levels of CitH3 were measured in serum samples of 160 critically ill patients with septic and non-septic shock, and healthy volunteers. Analyses of clinical and laboratory characteristics of patients were conducted. Results  Levels of circulating CitH3 at enrollment were significantly increased in septic shock patients (n = 102) compared to patients hospitalized with non-infectious shock (NIC) (n = 32, p