血浆组蛋白H4与脓毒症患者严重程度及预后关系研究

Prognostic value of plasma histone H4 in septic patients

目的:了解血浆组蛋白H4浓度是否与脓毒症患者严重程度有关,以及是否可作为判断脓毒症预后的指标。方法:采用前瞻性研究,观察2017年5月-2018年4月天津医科大学总医院急诊医学科50例脓毒症患者。收集脓毒症患者临床资料,采集患者入院24 h及72 h时血浆,通过酶联免疫分析检测血浆组蛋白H4和caspase-3浓度,并对血浆组蛋白H4与24 h及72 h时患者的疾病严重程度(APACHEⅡ评分、SOFA评分)、降钙素原(PCT)、C-反应蛋白(CRP)、乳酸(LAC)等临床指标进行相关性分析。按照患者预后将其分为存活组和死亡组,比较两组血浆组蛋白H4、caspase-3、评分和常用指标的差异,绘制ROC曲线评估血浆组蛋白H4等指标预测脓毒症患者预后的价值。结果:脓毒症患者死亡组24 h血浆组蛋白H4浓度高于存活组[505.80(462.46,657.85)vs408.09 (370.68,483.31),P<0.05],死亡组与存活组72 h血浆组蛋白H4浓度差异无统计学意义[429.95(354.12,557.70)vs 357.70(331.33,391.16),P>0.05]。存活组血浆组蛋白H4浓度72 h低于24 h[357.70(331.33,391.16)vs 408.09(370.68,483.31),P<0.05],死亡组血浆组蛋白H4浓度72 h和24 h差异无统计学意义[429.95 (354.12,557.70)vs(505.80(462.46,657.85),P>0.05]。脓毒症患者24 h时血浆组蛋白H4浓度与APACHEⅡ评分值(r=0.747,P<0.05)和SOFA评分值(r=0.631,P<0.05)呈正相关。对患者预后进行评估并绘制ROC曲线,血浆组蛋白H4的曲线下面积最高,AUC0.793,以452.661pg/mL为截断点时敏感性为88.9%,特异性为66.7%。24h及72h血浆组蛋白H4浓度均与PCT、CRP和caspase-3呈正相关(r值为0.429,0.306,0.735;0.359,0.354,0.732,P<0.05),而与PLT计数呈负相关(r值为-0.346,-0.436,P<0.05),72 h血浆组蛋白H4与LDH呈正相关(r=0.47,P<0.05)。结论:入院24 h血浆组蛋白H4浓度可反应脓毒症患者疾病严重程度,并作为判断预后的预测指标。

Objective: To discuss whether plasma H4 is correlated with the severity of septic patients and if levels of plasma H4 can be used as predictive markers for clinical outcome in sepsis. Methods: This prospective observational study enrolled 50 septic patients who were admitted to the Emergency department of Tianjin Medical University General Hospital. We collected patients’ clinical data and blood samples at 24 h and 72 h.We measured plasma H4 and caspase 3 levels by Enzyme-linked Immunosorbent Assay(ELISA)and analyzed their correlation with disease severity(APACHE Ⅱ score, SOFA score) by using clinical parameters including PCT,CRP and LAC levels,et al. The patients were divided into survival group and death group. The differences of plasma H4, caspase-3, score and clinical parameters were compared between survival group and death group. The ROC curve was drawn to evaluate the prognostic value of plasma histone H4 and other parameters of septic patients. Results: Median H4 levels in non-survivors was significantly higher than survivors at 24 h [28.25(25.48,42.17)vs 23.87(21.27,28.30),P <0.05]. There was no significant statistical difference in plasma histone H4 concentration between non-survivors and survivors at 72 h [429.95(354.12, 557.70)vs 357.70(331.33,391.16),P >0.05]. Plasma histone H4 concentration in survivors at 72 h was significantly lower than that at 24 h[357.70(331.33,391.16)vs408.09(370.68,483.31),P<0.05]. There was no significant statistical difference in plasma histone H4 concentration in non-survivors between 72 h and 24 h [429.95(354.12,557.70) vs 505.80(462.46,657.85),P>0.05].24 h Plasma H4 were positively correlated with apache ii score(r=0.747,P<0.05) and sofa score(r=0.631,P<0.05).The area under the ROC curve of plasma histone in predicting prognostic of sepsis was 0.79, higher than other parameters. The sensitivity was 88.9%,and the specificity was 66.7%. Both 24 h and 72 h plasma H4 were positively correlated with PCT,CRP and caspase-3(r=0.429,0.306, 0.735;0.359, 0.354, 0.732, P<0.05, P<0.05),while negatively correlated with PLT counts(r=-0.346,-0.436,P <0.05). The 72 h plasma H4 were positively correlated with LDH(r=0.47, P<0.05). Conclusion: Plasma histone H4 levels at 24 h are correlated with the severity in septic patients and it may be used as prognostic biomarker.