C-反应蛋白、中性粒细胞表面抗原CD64及血清淀粉酶A蛋白对极低出生体重儿败血症的早期诊断价值

Early diagnosis of sepsis with C-reactive protein, serum amyloid A and CD64 in very low birth weight infants

目的探讨C-反应蛋白（C-reactive protein，CRP）、血清淀粉酶A蛋白（serum amyloid A，SAA）、中性粒细胞表面抗原CD64在极低出生体重儿（very low birth weight infant，VLBWI）败血症早期诊断中的价值。方法2010年5月至2012年5月，温州医学院附属第二医院新生儿重症监护病房住院的54例临床疑似败血症的VLBWL在疑为败血症的0、24h分别取血；无感染性疾病的VLBWI作为对照组（20例），在相应日龄取血。采用酶联免疫吸附试验检测血清CRP和SAA表达。用流式细胞仪检测全血中性粒细胞表面抗原CD64水平。组间差异比较采用Mann-Whitney U检验。采用受试者工作特性曲线分析各指标预测败血症的敏感性和特异性。结果54例VLBWI临床疑似败血症，最终诊断败血症37例。败血症组CRP、SAA、CD64水平在0h时分别为13．3mg／L（4．6～67．2mg／L），95．7mg／L（4．5～265．9mg／L）和7306个荧光抗体分子／细胞（2667～10853个荧光抗体分子／细胞），均高于相应时间点对照组[分别为4．4mg／L（1．6～11．2mg／L）、7．3mg／L（2．5～16．9mg／L）和2502个荧光抗体分子/细胞（1839～3017个荧光抗体分子/细胞）]，差异均有统计学意义（Z分别为-2．308、2．425和-3．704，P均〈0．05）；败血症组CRP、SAA、CD64水平在24h时分别为35．4mg／L（7．7～106．5rag／L），359．3mg／L（3．8--503．2mg／L）和8304个荧光抗体分子／细胞（2819～11758个荧光抗体分子／细胞），均高于相应时间点对照组[分别为3．2mg／L（1．1～7．8mg／L）、6．6mg／L（3．0～12．7mg／L）和2563个荧光抗体分子/细胞（1760～3154个荧光抗体分子／细胞）]，差异均有统计学意义（z分别为-5．501、-2．818和-7．670，P均〈0．05）。CD64诊断败血症的最佳界值为2934个荧光抗体分子/细胞，在0、24h，CD64诊断败血症的敏感性分别为81．1％、91．9％，特异性分别为90．0％、80．0％，SAA的敏感性（83．8％和86．5%）与CD64相似，但特异性（65．0％和55．0％）较CD64低，CRP的敏感性（62．2％和70．3％）及特异性（70．0％和70．0％）均较低，若三种指标联合检测，其敏感性（91．9%和97．2％）和特异性（95．0％和90．0％）均较高。结论CRP、SAA和CD64联合检测有利于提高对VLBWI败血症的诊断准确性。

Objective To investigate the value of C reactive protein （CRP）, serum amyloid A （SAA） and CD64 in early diagnosis of sepsis in very low birth weight infants （VLBWI）. Methods Fifty-four VLBWI suspected to sepsis and 20 VLBWI without infection in neonatal intensive care unit of the Second Hospital of Wenzhou Medical College from May 2010 to May 2012 were enrolled in this study. CRP, SAA and CD64 of sepsis group were measured at 0 and 24 hour after suspected bacterial infection; and those of control group were measured at corresponding age. CRP and SAA were detected by enzyme-linked immunosorbent assay, and CD64 was detected by flow cytometry. The difference between groups was compared by Mann-Whitney U test. Receiver operating characteristic curve was used to predict the sensitivity and specificity of the three biomarkers on sepsis.Results Fifty-four VLBWI were suspected with sepsis, and 37 patients were finally diagnosed. The levels of the three hiomarkers in sepsis group were higher than those of control group not only at 0 h ECRP： 13.3 rag/L（4.6 67.2 mg/L） vs 4.4 rag/L（1.6-11.2 mg/L）, Z=-2.308; SAA： 95.7 mg/L（4.5 265.9 mg/L） vs 7.3 rag/L（2.5 16.9 mg/L）, Z=-2. 425; CD64：7306 fluorescent antibody molecules/cell （2667-10 853 fluorescent antibody molecules/cell） vs 2502 fluorescent antibody molecules/cell （1839-3017 fluorescent antibody molecules/cell）, Z =-3. 704], but also at 24 h ECRP： 35.4 mg/1. （7.7 106.5 mg/L） vs 3.2 mg/L （1.1-7.8 mg/L）, Z=-5. 501; SAA： 359.3 mg/L （3.8-503.2 mg/L） vs 6.6 mg/L （3.0-12.7 mg/L）, Z 2.818; CD64： 8304 fluorescent antibody molecules/ceil （2819-11 758 fluorescent antibody molecules/cell） vs 2563 fluorescent antibody molecules/cell （1760-3154 fluorescent antibody molecules/cell）, Z=7. 670], P 〈 0.05 respectively. The best cutoff value of CD64 was 2934 fluorescent antibody molecules/cell, with the sensitivity of 81.1% at 0 h and 91.9% at 24 h; and the specificity of 90.0% at 0 h and 80.0% at 24 h. Although SAA had similar sensitivity （0 h： 83.8%; 24 h： 86.5%） as CD64, its specificity was relatively low（0 h： 65.0%; 24 h： 55.0%）. Both the sensitivity （0 b： 62.2%; 24 h： 70.3%） and specificity （0 h： 70.0%; 24 h： 70.0%） of CRP were low. Combination of the three infection biomarkers could increase the sensitivity （0 h： 91.9%; 24 h： 97.2%） and specificity （0 h ： 95.0 % ; 24 h ： 90.0 % ）. Conclusions Combination of CRP, SAA and CD64 might improve the diagnostic accuracy of sepsis in VLBWL