严重发热伴血小板减少综合征疾病程度的相关实验室指标筛选  

The severity predictive index selection of severe fever with thrombocytopenia syndrome

作　　者：韩亚萍[1] 陈念[1] 金柯[1] 李军[1] 蒋龙凤[1] 杜兴冉[1] 蔡洁[1] 董莉[1] 周宜庆 黄祖瑚[1] 

机构地区：[1]南京医科大学第一附属医院感染病科,210029

出　　处：《中华检验医学杂志》2015年第1期49-54,共6页Chinese Journal of Laboratory Medicine

基　　金：国家重大科技专项（2013ZX10002005-002-005,2013ZX10004905）;江苏省医学创新团队与领军人才项目（LJ201121）;江苏省科技支撑计划（BE2012770）;江苏高校优势学科建设工程（JX10231801）

摘　　要：目的联合检测严重发热伴血小板减少综合征（SFTS）患者，血清病毒载量、淋巴细胞亚群、血清酶学及血细胞计数；应用Logistic回归分析和ROC曲线，建立SFTS疾病严重程度综合评估方法。方法病例对照研究。收集南京医科大学第一附属医院2011年5月至2012年7月SFTS患者24例，诊断标准参照原中华人民共和国卫生部发布的发热伴血小板减少综合征防治指南（2010版），按照疾病严重程度分为轻中症组（16例）和重症组（8例），32名健康对照者均为南京市中心血站健康献血者。采用流式细胞术检测健康对照者及SFTS患者外周血中CD3＋、CD4＋、CD8＋淋巴细胞以及CD3-CD16＋CD56＋即自然杀伤细胞（NK细胞）；流式液相多重蛋白定量（CBA）技术定量检测血清中Th1／Th2／Th17细胞因子；采用荧光定量PCR技术，动态检测SFTS患者外周血中严重发热伴血小板减少综合征病毒（SFTSV）载量，同时检测白细胞、血小板和血清酶学指标；建立Logistic回归分析的多指标联合模型及ROC曲线，分析各指标对SFTS疾病严重程度的预测价值。结果单一指标的ROC分析发现SFTSVRNA、CD3、CD4、CD8、CD56、AST、乳酸脱氢酶（LDH）、CK、白细胞介素石（IL-6）和IL—10对SFrS早期预测疾病严重程度有较好的预测价值，AUC分别为0．83、0．84、0．90、0．75、0．94、0．73、0．78、0．87、0．74和0．77，其中SFTSV载量、CD3＋、CIM＋、NK细胞和CK的cut—off值分别为6．19log 10拷贝／ml、57．51％、19．47％、15．71％和696．45U／L。用逐步法Logistic回归分析构建模型，并对预测概率进行ROC曲线分析发现，SFTSVRNA／cD3／cD4／cD8／cD56、SFTSVRNA／AST／LDH／CK、SFTSVRNA／IL-6／IL-10联合指标模型的预测价值有所提高，ROC曲线下面积分别为0．95（95％CI：0．00～1．00）、0．87（95％CI：0．75～0．99）、0．83（95％CI：0．70～0．97），敏感度分�Objective To detect the serum viral load, lymphocyte subsets, serum enzymes and blood cell counts of severe fever with thrombocytopenia syndrome （ SFTS ） patients, and to use logistic regression analysis and receiver operating characteristic （ROC） curve to establish a model to analyze the severity of SFTS. Methods A case-control study of 24 SFTS cases admitted between May 2011 and July 2012 was conducted at the First Affiliated Hospital of Nanjing Medical University. All SFTS cases were defined according to Fever with Thrombocytopenia Syndrome Prevention and Control Guidelines （2010 edition） issued by the Ministry of Health of the People＇ s Republic of China. According to their disease severity, the patients were divided into two groups, the non-severe group （16 cases） and the severe group （8 cases）. In addition, 32 healthy volunteers were also enrolled in this study. Flow cytometry was adopted to detect the CD3 ＋ , CD4 ＋ , CD8 ＋ lymphocytes and CD3 - CD16 ＋ CD56 ＋ natural killer cells （ NK cells） in the peripheral blood of SFTS patients, and cytometric beads array （CBA） was used to detect Th1/Th2/ Thl7 cytokines. The serum viral load in patients with severe fever with thrombocytopenia syndrome virus （SFTSV） infection was detected by fluorescent quantitative PCR technology. Besides, white blood ceils, platelets and serum enzymes were measured. The multi-index conjunctive model of logistic regression analysis and receiver operating characteristics （ROC） curve were used to analyze the predictive values of indexes on severity of SFTS. Results The ROC analysis of single index found that SFTSV RNA, CD3, CD4, CD8, CD56, AST, LDH, CK, IL-6 and IL-10 have good predictability on severity of SFTS in the early course of the disease; the area under the curve （AUC） were 0. 83, 0. 84, 0. 90, 0. 75, 0. 94, 0. 73,0. 78, 0. 87, 0. 74 and 0. 77 respectively, and the cut-off values of the SFTSV load, CD3 ＋ , CD4 ＋ , NK cells and CK were 6. 19 log10 copies/ml, 57.51%, 19.47%, 1

关 键 词：布尼亚病毒科感染 杀伤细胞 天然 细胞因子类 病毒载量 疾病严重程度 指数 ROC曲线 

分 类 号：R511[医药卫生—内科学] R440[医药卫生—临床医学]