目的 探讨外周血CD20+CD24hi CD38hi调节性B细胞(Bregs)水平对老年脓毒症患者预后的评估价值.方法 采用前瞻性研究方法,选择2016年4月至2017年2月入住同济大学附属东方医院急诊内科和急诊重症加强治疗病房(ICU)符合Sepsis-3诊断标准、年龄>65岁的老年脓毒症患者.常规检测降钙素原(PCT)、C-反应蛋白(CRP)和动脉血乳酸(Lac)水平,并根据24 h内指标最差值计算急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分和序贯器官衰竭评分(SOFA);于入院1、3、7 d采用流式细胞仪检测外周血CD20+CD24hi CD38hi Bregs表达水平.根据28 d预后将患者分为存活组和死亡组,比较两组各指标的差异;对差异有统计学意义的变量进行二元logistic回归分析;用Spearman法分析Bregs与各指标的相关性;用受试者工作特征曲线(ROC)分析Bregs对老年脓毒症患者预后的评估价值.结果 入选58例患者,其中男性38例,女性20例;年龄(79.91±7.97)岁;脓毒症32例,脓毒性休克26例;死亡35例,病死率为60.3%.死亡组APACHEⅡ评分、SOFA评分显著高于存活组〔APACHEⅡ(分):18.14±4.52比14.91±3.56,SOFA(分):8.80±4.56比6.35±3.00,均P<0.05〕,1、3、7 d外周血Bregs表达水平均显著低于存活组〔个/μL:0.70(0.20,1.40)比1.50(0.70,2.20),0.54(0.20,1.00)比1.42(1.10,2.12),0.25(0.10,0.50)比0.80(0.50,1.00),均P<0.05〕.老年脓毒症患者入院1 d外周血Bregs与APACHEⅡ评分呈显著负相关(r=-0.351,P=0.007),与PCT、CRP、Lac和SOFA评分无相关性.二元logistic回归分析显示,Bregs〔优势比(OR)=1.865,P=0.028〕和APACHEⅡ评分(OR=0.853,P=0.026)是影响老年脓毒症患者预后的独立危险因素.ROC曲线分析显示,入院1、3、7 d Bregs和APACHEⅡ评分对老年脓毒症患者预后的预测价值均较高,ROC曲线下面积(AUC)和95%可信区间(95%CI)为0.842(0.647~0.954)、0.770(0.564~0.911)、0.888(0.703~0.977)和0.855(0.661~0.961),均P<0.01;入院7 d Bregs的AUC最大,截断值为0.50个/μL时敏感度为72.73%,特异度为86.67%.结论 外周血CD20+CD24hi CD38hi Bregs表达水平在一定程度上可以用于判断老年脓毒症患者的预后.%Objective To explore the predicting value of peripheral blood CD20+ CD24hi CD38hi regulatory B cells (Bregs) on the prognosis of elderly patients with sepsis.Methods A prospective study was conducted. Septic patients aged > 65 years old, compliance with diagnostic criteria for Sepsis-3, admitted to emergency and emergency intensive care unit (ICU) of Shanghai East Hospital of Tongji University from April 2016 to February 2017 were enrolled. Procalcitonin (PCT), C-reaction protein (CRP) and lactate (Lac) were routinely measured. According to the worst clinical index value within 24 hours, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sequential organ failure assessment (SOFA) score were recorded. The concentrations of peripheral blood CD20+ CD24hi CD38hi Bregs were measured by flow cytometry at 1, 3 and 7 days after diagnosed in elderly patients. All patients with sepsis were followed up for 28 days and then divided into death group and survival group according to 28-day outcome. The difference of clinic data and Bregs were compared between the two groups. The significant different factors of elderly sepsis patients were analyzed by binary logistic regression analysis. The correlation between Bregs level and other indicators was analyzed by Spearman correlation. The receiver operating characteristic curve (ROC) was used to evaluate the prognosis value of Bregs in elderly patients with sepsis.Results Fifty-eight patients were enrolled in the study, with 38 male and 20 female; age of (79.91±7.97) years; 32 in sepsis group, 26 in septic shock group; 35 deaths, 28-day mortality rate was 60.3%. APACHE Ⅱ score and SOFA score in death group exhibited much higher than that in survival group (APACHE Ⅱ: 18.14±4.52 vs. 14.91±3.56, SOFA: 8.80±4.56 vs. 6.35±3.00, bothP < 0.05), the Bregs was significantly decreased at 1, 3 and 7 days in death group [cells/μL: 0.70 (0.20, 1.40) vs. 1.50 (0.70, 2.20), 0.54 (0.20, 1.00) vs. 1.42 (1.10, 2.12), 0.25 (0.10, 0.50) vs. 0.80 (0.50, 1.00), allP < 0.05]. Correlation analysis showed that the concentrations of peripheral blood Bregs at 1 day in elderly patients with sepsis was negatively correlated with APACHE Ⅱ score (r = -0.351,P = 0.007), and it was not correlated with PCT, CRP, Lac or SOFA score. It was shown by binary logistic regression that Bregs [odds ratio (OR) = 1.865,P = 0.028] and APACHE Ⅱ score (OR = 0.853,P = 0.026) were independent risk factors for elderly sepsis outcome. It was shown by ROC curve analysis that the prognostic value of the levels of Bregs at 1, 3, 7 days and APACHE Ⅱ score were higher in the elderly patients with sepsis, and the area under ROC curve (AUC) and 95% confidence interval (95%CI) were 0.842 (0.647-0.954), 0.770 (0.564-0.911), 0.888 (0.703-0.977), 0.855 (0.661-0.961), respectively, allP < 0.01. The 7-day Bregs was most powerful to predict outcome, when the cut-off value was 0.50 cells/μL, the sensitivity was 72.73% and specificity was 86.67%. Conclusions The level of peripheral blood CD20+ CD24hi CD38hi Bregs could predict the clinical outcome of elderly patients with sepsis.
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