Department of Surgery, University of Michigan Health System, University of Michigan Medical School, 1500 E Medical Center Dr. SPC 5331, Ann Arbor, MI, 48109-5331, USA.
Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Infection. 2021 Feb;49(1):83-93. doi: 10.1007/s15010-020-01528-y. Epub 2020 Sep 30.
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.
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.
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 < 0.0001). The area under the curve (95% CI) for distinguishing septic shock from NIC using CitH3 was 0.76 (0.65-0.86). CitH3 was positively correlated with PAD2 and PAD4 concentrations and Sequential Organ Failure Assessment Scores [total score (r = 0.36, p < 0.0001)]. The serum levels of CitH3 at 24 h (p < 0.01) and 48 h (p < 0.05) were significantly higher in the septic patients that did not survive.
CitH3 is increased in patients with septic shock. Its serum concentrations correlate with disease severity and prognosis, which may yield vital insights into the pathophysiology of sepsis.
微生物感染刺激中性粒细胞/巨噬细胞/单核细胞细胞外陷阱的形成，这导致由肽基精氨酸脱亚氨酶（PAD）2 和 4 催化的瓜氨酸化组蛋白 H3（CitH3）的释放。了解这些分子机制在脓毒性休克的发病机制中，对于开发新的诊断和治疗方法将是重要的下一步。我们试图确定脓毒性休克患者中 CitH3 的表达，并将 CitH3 水平与 PAD2/PAD4 和临床相关结局相关联。
在患有脓毒症和非脓毒性休克的 160 名危重症患者和健康志愿者的血清样本中测量 CitH3 水平。对患者的临床和实验室特征进行分析。
与患有非感染性休克（NIC）的患者（n=32，p<0.0001）相比，患有脓毒性休克的患者（n=102）在入院时循环 CitH3 水平显着升高。使用 CitH3 区分脓毒性休克与 NIC 的曲线下面积（95%CI）为 0.76（0.65-0.86）。CitH3 与 PAD2 和 PAD4 浓度和序贯器官衰竭评估评分呈正相关[总分（r=0.36，p<0.0001）]。在未存活的脓毒症患者中，CitH3 的血清水平在 24 小时（p<0.01）和 48 小时（p<0.05）时显着升高。
CitH3 在脓毒性休克患者中增加。其血清浓度与疾病严重程度和预后相关，这可能为脓毒症的病理生理学提供重要的见解。
