可溶性CD163和CD25在儿童噬血细胞性淋巴组织细胞增生症诊治中的意义

Significance of soluble CD163 and soluble CD25 in diagnosis and treatment of children with hcmophagocytic lymphohistiocytosis

目的探讨血清可溶性CD163（sCD163）和可溶性CD25（sCD25）在儿童噬血细胞性淋巴组织细胞增生症（HLH）诊断及指导治疗中的意义。方法收集2013年12月至2014年12月郑州大学第一附属医院儿科门诊及病房就诊的HLH患儿42例，非HLH感染患儿32例及正常对照组儿童24名。HLH患儿分别于治疗前、治疗后2周、治疗后8周3个时间点各采集清晨空腹外周静脉血3ml，非HLH感染组患儿及正常对照组儿童于首次就诊时采集外周静脉血3ml，采用酶联免疫吸附试验（ELISA）方法检测3组患儿外周血血清sCD163和sCD25水平，分析血清sCD163与sCD25水平在3组之间的差异，治疗前后的变化趋势及对HLH的诊断效能；根据发病因素将HLH组患儿分为感染相关性HLH、肿瘤相关性HLH、原发性HI．H及其他，分析血清sCDI63与sCD25水平与HLH相关发病因素的关系。结果HLH组患儿血清sCD163[（6094±2769）μg／L]和非HLH感染组患儿血清sCD163[（2174±950）μg/L]均明显高于正常对照组f（777±256）ng／L]，3组间差异有统计学意义（F=71．396，P〈0．05），且各组之间两两比较差异均有统计学意义（P〈0．05）；HLH组患儿血清sCD25[（41963±31821）ng／L]和非HLH感染组患儿血清sCD25[（6700±4105）ng／L]均明显高于正常对照组[（2440±1870）ng／L]，3组间差异有统计学意义（F=37．513，P〈0．05），非HLH感染组与正常对照组差异无统计学意义（P〉0．05），其余各组比较差异有统计意义（P〈0．05）。HLH组患儿血清sCD163和sCD25水平呈线性正相关，Pearson相关系数r=0．742（t=7．000，P〈0．05）。HLH组不同的发病因素之间血清sCD163和sCD25水平差异有统计学意义（X^2=14．221、8．075，P〈0．05）；且肿瘤相关性HLH组血清sCD163和sCD25水平较感染相关性HLH组明显升高（t=3．976、3．063，P〈0．05），而其余各组之间比较差异均无统计学意义（均P〉0．05）。19例接受HLH-2004治疗的HLH组患儿血清sCD163和sCD25水平在治疗前、治疗2周、治疗8周分别为sCD163：（5604±2681）、（3191±1697）、（1031±522）μg／L；sCD25：（36416±27479）、（21372±15835）、（3185±1855）ng／L，下降趋势差异有统计学意义（P〈0．05）。当血清sCD163的切值为2359．08μg／L时，诊断HLH的灵敏度为83．3％，特异度为83．9％；当血清sCD25的切值为14901．024ng／L时，诊断HI。H的灵敏度为76．2％，特异度为98．2％。结论血清sCD163与sCD25可用于HLH的诊断；血清sCDI63和sCD25水平可能为肿瘤相关性HLH与其他原因相关HLH的鉴别提供线索；动态监测HLH患儿血清sCD163和sCD25水平有助于判断病情恶化及指导治疗。

Objective To explore significance of serum soluble CD163 （ sCD163 ） and soluble CD25 （ sCD25 ） in diagnosis and guiding treatment of children with hemophagoeytic lymphohistioeytosis （ HLH ）. Method Data of 42 cases of children with HLH, 32 cases of non-HLH children with infection presented to First Affiliated Hospital of Zhengzhou University pediatric clinic and ward were collected from December 2013 to December 2014. Twenty-four healthy children were enrolled into a normal control group in the same period. Peripheral venous blood specimens （3 ml） were taken from the children with HLH after fasting before treatment, two weeks after treatment and eight weeks after treatment. Peripheral venous blood specimens （ 3 ml） were also taken from children of non-HLH infected group and normal control group after fasting at the initial visit. Serum sCD163 and sCD25 levels in the peripheral blood in three groups were determined by ELISA. According to cause of disease, children with HLH were divided into infection-related HLH, tumorrelated HLH, primary HLH and others; relationship between serum sCD163 and sCD25 level and cause of disease was analyzed. Result Serum sCD163 of HLH group （ （6 094 ±2 769） μg/L） and serum sCD163 of non-HLH infection group （ （2 174 ±950） μg/L） were significantly higher than that of normal control group （（777 ± 256 ） μg/L）, F = 71. 396, P 〈 0. 05 ）, and the differences among groups were statistically significant （ P 〈 0. 05） ; serum sCD25 of HLH group （ （41 963 ± 31 821 ） ng/L） arid serum sCD25 of non- HLH infection group （ （6 700 ± 4 105 ） ng/L） were significantly higher than that of normal control group （ （2 440 ± 1 870） ng/L, F = 37. 513, P 〈 0. 05 ）. There was no statistically significant difference between the non-HLH infection group with the normal control group （ P 〉 0. 05 ）, and the difference between the remaining groups was statistically significant （P 〈 0. 05 ）. And serum sCD163 and sCD25 level of HLH group had a positive linear correlation, and Pearson correlation coefficient r = 0.742 （ t = 7.000, P 〈 0.05 ）. The difference of serum sCD163 and sCD25 level among the different cause of disease in HLH group was significant （P 〈 0. 05）. Pairwise comparison showed that serum sCD163 and sCD25 level of tumor-associated HLH group significantly increased as compared with infection-associated HLH group （ P 〈 0. 05 ）, but the difference was not statistically significant between the other groups （ all P 〉 0. 05 ）. Serum sCD163 and sCD25 level of HLH group before treatment, 2 weeks and 8 weeks after treatment showed a statistically significant tendency of decrease （P 〈 0. 05）. Seen from the ROC curve, when sCD163 cut-off point was 2 359.08 μg/L, the diagnostic sensitivity was 83.3% , and specificity was 83.9%. When sCD25 cut-off point was 14 901. 024 ng/L, the diagnosis sensitivity was 76. 2% , and specificity was 98.2%. Conclusion Serum sCD163 and sCD25 levels may be used for diagnosis of HLH. Dynamically monitoring of serum sCD163 and sCD25 level can help to determine deterioration of HLH and guide treatment.