腺苷脱氨酶在儿童EB病毒相关噬血细胞综合征中的意义

Significance of Adenosine Deaminase for EB Virus-associated Hemophagocytic Lymphohistiocytosis in Children

目的探讨血清中腺苷脱氨酶(ADA)水平在儿童EB病毒感染相关噬血细胞综合征(EBV-HLH)中的诊断及预后判断价值。方法选取2015年1月~2017年12月期间浙江大学医学院附属儿童医院收治的初诊EBV-HLH患者72例和慢性活动性EB病毒(CAEBV)感染患儿80例,HLH患者均符合HLH-2004诊断标准,同期50例健康体检儿童作为健康对照组。应用全自动生化分析仪测定各组患者血清ADA水平,采用受试者工作特征曲线(ROC)分析ADA临床诊断价值,Youden指数法确定最佳工作点。结果EBV-HLH组、CAEBV组及健康对照组儿童血清ADA水平分别为102.4±64.9U/L、42.8±22.1U/L和13.3±3.2U/L。EBV-HLH组ADA水平明显高于CAEBV组,差异有统计学意义(Z=4.709,P=0.000);CAEBV组高于健康对照组,差异有统计学意义(Z=5.008,P=0.000)。以慢性活动性EBV感染组为对照组,利用ROC曲线分析ADA在EBV-HLH中的诊断价值,曲线下面积最高为0.893(P=0.000),以57.5U/L为阈值时,敏感度为74.7%,特异性为89.1%,阳性预测值和阴性预测值分别为90.3%、72.1%。在EBV-HLH组中,ADA与EBV拷贝数呈正相关(r=0.608,P=0.000)。10例EBV-HLH死亡患儿血清ADA水平明显高于存活患儿(154.2±47.3U/L vs 92.5±63.4U/L,P=0.002)。结论血清ADA水平可作为EBV-HLH诊断的常规辅助项目,且在与慢性活动性EBV感染鉴别诊断中具有重要意义。

Objective To investigate the diagnostic and prognostic value of adenosine deaminase(ADA)level in children with EBV-associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods Between January 2015 and December 2017,72 patients with EBV-HLH and 80 patients with chronic active EBV infection(CAEBV)admitted to Children′s Hospital Zhejiang University School of Medicine were selected.All HLH patients met the HLH-2004 diagnostic criteria,and 50 healthy children in the same period served as healthy control group.The ADA levels of serum samples were measured by automatic biochemical analyzer.The clinical diagnostic value of ADA was analyzed by ROC curve.The Youden index method was used to determine the best working point.Results The ADA levels of serum in EBV-HLH group,CAEBV group and healthy control group were 102.4±64.9U/L、42.8±22.1U/L and 13.3±3.2U/L respectively.The ADA level in EBV-HLH group was significantly increased than that in CAEBV group(Z=4.709,P=0.000)and that in CAEBV group was higher compared with healthy control group(Z=5.008,P=0.000).The chronic active EBV infection group as a control group,we calculated the area under ROC curve of ADA in EBV-HLH was 0.893(P=0.000).The sensitivity and specificity of ADA were 74.7%and 89.1%when the threshold value was 57.5U/L.Positive predictive value and negative predictive value were 90.3%and 72.1%,respectively.In EBV-HLH group,ADA was positively correlated with copy number of EBV(r=0.608,P=0.000).The subgroup analysis indicated that the serum level of ADA were significantly higher in dead patients than those in survived patients(154.2±47.3U/L vs 92.5±63.4U/L,P=0.002).Conclusion Serum ADA level can be used as a routine ancillary item in the diagnosis of EBV-HLH,and is of great significance in the differential diagnosis of chronic active EBV infection.