CD163对儿童感染相关性噬血细胞综合征的诊断及预后判断价值

Diagnostic and prognostic value of CD163 for infection - associated hemophagocytic syndrome in children

目的探讨血清可溶性CD163（soluble CD163，sCD163）和外周血单核细胞膜性CD163（membrane－bound CD163，mCD163）表达对儿童感染相关性噬血细胞综合征（infection associated hemophagocytic syndrome，IAHS）诊断及预后判断的价值。 方法研究对象为2012年7月至2016年6月上海交通大学附属儿童医院重症医学科收治的IAHS患儿26例（IAHS组）和脓毒症患儿28例。采用双抗体夹心酶联免疫吸附法及流式细胞术检测2组患儿血清sCD163水平和外周血单核细胞mCD163表达率。选择20例健康体检儿童作为健康对照组。采用受试者工作特征曲线（ROC）分析sCD163和mCD163临床诊断价值，Youden指数法确定最佳工作点，并与铁蛋白等传统指标对比分析。 结果IAHS组、脓毒症组及健康对照组儿童血清sCD163水平及外周血单核细胞mCD163表达率分别为（1 264±538） mg/L、（ 862±332） mg/L、（610±316） mg/L和（88.3±9.7）%、（68.5±18.3）%、（28.9±5.2）%，IAHS组血清sCD163水平及mCD163表达率明显高于脓毒症组，差异有统计学意义（t＝2.031, P＝0.048; t＝3.191, P＝0.002）；脓毒症组高于健康对照组，差异有统计学意义（t＝3.848，P＝0.002; t＝4.049, P＝0.000）。mCD163在诊断IAHS中ROC曲线下面积最高为0.853（P＝0.013），sCD163及铁蛋白分别为0.762（P＝0.004）、0.755（P＝0.049）。mCD163以83.7%为阈值时，敏感度为81.8%，特异度为72.4%；sCD163以888 mg/L为阈值时，敏感度为66.7%特异度为63.3%；铁蛋白阈值为2 880 μg/L时，敏感度为80.0%，特异度为54.5%。IAHS组患儿急性期血清sCD163水平及外周血单核细胞mCD163表达率明显高于治疗后病情好转患儿[（1 553±542） mg/L比（866±92） mg/L，t＝2.456，P＝0.036；（91.0±6.4）%比（79.0±4.6）%，χ2＝3.419，P＝0.007]; 9例IAHS死亡患儿sCD163和mCD163表达水平高于存活患儿[（1 748.91±518.17） mg/L比（909.69±171.35） mg/L，t＝3.070，P＝0.018；（93.50±8.42）%比（77.30±3.28）%，χ2＝3.005，P＝0.024]。 结论血清sCD163水平及外周血单核细胞mCD163表达水平可能是诊断儿童IAHS的特异性指标，对预测IAHS疗效及评估预后有参考价值。

Objective To investigate the diagnostic and prognostic value of serum soluble CD163 （ 8CD163 ） and the positive rate of membrane - bound CD163 （ mCD163 ） in peripheral blood mononuclear cells （PBMC） in children with infection -associated hemophagocytic syndrome （IAHS）. Methods Between July 2012 and June 2016,26 pediatric patients with IAHS （IAHS group） and 28 pediatric patients with sepsis（ sepsis group）admitted to Children＇s Hospital Affiliated to Shanghai Jiaotong University were selected, and 20 healthy children were taken as healthy control group. Sandwich enzyme linked immunosorbent assay was used to detect serum sCDl63. The population of circulating mCDI63 positive monocytes was determined by using flow cytometry. Receiver operating characteristic （ROC） curves were used to evaluate the diagnostic and prognostic values of sCD163 and mCD163 in children with IAHS compared with the diagnos- tic and prognostic values of plasma ferritin,and so on. Results The serum levels of sCD163 in patients of IAHS group, sepsis group and healthy control group were （ 1 264±538） rag/L, （862 ± 332） mg/L, （610±316） mg/L,respectively. And the population of mCD163 - positive PBMC in patients of IAHS group ,sepsis group and healthy control group was （88.3± 9.7 ） %, （68.5 ±18.3 ） %, （28.9 ± 5.2） %, respectively. Both serum sCD^63 and the population of mCD163 - positive PBMC were significantly higher in IAHS group compared with those of sepsis group （ t = 2.031, P = 0. 048 ; t =3. 191, P = 0. 002, respectively）. The serum sCD163 and population of mCDI63 -positive PBMC in sepsis group were higher than controls （ t = 3. 848, P = 0. 002; t = 4. 049, P = 0. 000, respectively）. Moreover,the areas under the ROC curve （AUC） for the mCD163 ,sCD163 ,were 0. 853（P =0.013） ,0.762（P =0.004） ,0.755 （P =0.049） ,respectively, mCD163 at a cutoff of 83.7% had a high diagnosis sensitivity （81.8%） and specificity （72.4%）. The optimal cutoff values of sCDI63 and ferritin for predicting IAHS was 888 mg/L （ sensitivity 66.7% and specificity 63.3% ） and 2 880 g/L （sensitivity 80.0% and specificity 54.5% ）. In addition,the serum level of sCD163 and the population of mCDI63 -positive PBMCs were significantly increased in acute phase and decreased in recovery phase[ （1 553 ± 542 ） mg/L vs. （866 ±92） mg/L,（91.0±6.4）% vs. （79.0 ±4.6）% ,t =2.450,X2 =3.419,P=0.036,0.007] in IAHS group. Furthermore, subgroup analysis indicated that the serum level of sCDl63 and the population of mCDi63 -positive PBMCs were significantly higher in dead patients than those in survived patients [ （ 1 748.91 ± 518.17） mg/L vs. （909.69± 171.35） mg/L,t =3.070,P =0.011 ; （93.50±8.42）% vs. （77.30 ±3.28）% ,X2 =3. 005,P=0. 024, respectively ]. Conclusion Serum sCDI63 and the population of mCD163 -positive PMSCs are speeifie and validity bio- markers for early diagnosis of IAHS,whieh also are associated with treatment response assessment and prognostic analysis in IAHS.