Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate with disease severity.
Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate with disease severity.
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血清瓜氨酸化组蛋白H3浓度可区分感染性休克和非感染性休克患者，并与疾病严重程度相关。
DOI：
10.1007/s15010-020-01528-y
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发表时间：
2021-03
期刊：
影响因子：
7.5
通讯作者：
Alam HB
中科院分区：
文献类型：
--
作者：
Tian Y;Russo RM;Li Y;Karmakar M;Liu B;Puskarich MA;Jones AE;Stringer KA;Standiford TJ;Alam HB
微生物感染刺激中性粒细胞/巨噬细胞/单核细胞胞外陷阱形成，这导致由肽基精氨酸脱亚胺酶（PAD）2和4催化的瓜氨酸化组蛋白H3（CitH3）释放。了解感染性休克发病机制中的这些分子机制将是开发新型诊断和治疗方法的重要下一步。我们试图确定感染性休克患者中CitH3的表达，并将CitH3水平与PAD2/PAD4以及临床相关结果相关联。
在160名患有感染性和非感染性休克的重症患者以及健康志愿者的血清样本中测量了CitH3的水平。对患者的临床和实验室特征进行了分析。
与因非感染性休克（NIC）住院的患者（n = 32，p < 0.0001）相比，感染性休克患者（n = 102）入组时循环CitH3水平显著升高。使用CitH3区分感染性休克和NIC的曲线下面积（95%置信区间）为0.76（0.65 - 0.86）。CitH3与PAD2和PAD4浓度以及序贯器官衰竭评估分数[总分（r = 0.36，p < 0.0001）]呈正相关。在未存活的感染患者中，24小时（p < 0.01）和48小时（p < 0.05）的血清CitH3水平显著更高。
CitH3在感染性休克患者中升高。其血清浓度与疾病严重程度和预后相关，这可能对脓毒症的病理生理学产生重要见解。
本文的在线版本（10.1007/s15010 - 2020 - 01528 - y）包含补充材料，可供授权用户使用。
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. The online version of this article (10.1007/s15010-020-01528-y) contains supplementary material, which is available to authorized users.
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