川崎病急性期白细胞介素-6、N端脑钠肽前体和铁蛋白变化的临床意义

Clinical Significance of Circulation Interleukin 6,N-terminal Pro-brain Natriuretic Peptide and Ferritin in Acute Kawasaki Disease

目的观察川崎病患儿急性期血清白细胞介素-6(IL-6)、N端脑钠肽前体(NT-pro BNP)和铁蛋白的变化,探讨其在辅助诊断川崎病中的意义,与丙种球蛋白(IVIG)无反应和冠状动脉损害(CALs)的关系。方法选取2014年10月~2016年2月在笔者医院儿科住院的急性期川崎病患儿108例为研究对象(男性64例,女性44例),年龄2月龄~11岁5月龄。根据发热10天内使用IVIG的效果,分为IVIG敏感组(81例)和IVIG无反应组(27例);并根据有无冠状动脉损伤分为CALs组(31例)和非CALs组(nCALs,77例)。选取同期住院的感染发热患儿30例为对照组(男性18例,女性12例);患者年龄4月龄~10岁。应用电化学发光法检测患儿入院当天血清IL-6和NT-pro BNP水平,免疫比浊法检测铁蛋白水平。比较分析川崎病急性期与对照组、IVIG敏感组和IVIG无反应组以及CALs和nCALs组各指标的变化,对两组间比较差异有统计学意义的指标进行受试者工作特征(receiver operating characteristic,ROC)曲线分析。结果 (1)川崎病患儿急性期血清IL-6、NT-pro BNP和铁蛋白水平分别为135±268ng/L,1008±1675ng/L和227±238μg/L,均高于对照组27±29ng/L(t=2.192,P=0.03),109±100ng/L(t=5.463,P=0.000)和72±101μg/L(t=3.437,P=0.001)。(2)IVIG敏感组和IVIG无反应组中IL-6和铁蛋白水平,差异无统计学意义。IVIG无反应组NT-pro BNP水平1837±2666ng/L明显高于IVIG敏感组721±1032ng/L(t=3.108,P=0.002)。(3)CALs组和nCALs组血清IL-6水平,差异无统计学意义。CALs组NT-pro BNP1703±2569ng/L vs 742±1080ng/L,铁蛋白340±405μg/L vs 183±99μg/L,水平高于nCALs组(P均<0.05)。(4)IL-6,NT-pro BNP和铁蛋白辅助诊断川崎病的ROC曲线下面积分别为为0.773、0.835和0.793。NT-pro BNP判断川崎病-IVIG无反应的ROC曲线下面积为0.623。NT-pro BNP和铁蛋白判断CALs的ROC曲线下面积分别为0.612和0.671;铁蛋白判断CALs的ROC曲线下面积甚至优于NT-pro BNP,临界值160.2μg/L时,判断CALs的敏感度和特异性分别为73.7%和52.1%。结论川崎病患儿急性期血清IL-6、NT-pro BNP和铁蛋白水平显著增加,可作为辅助川崎病早期诊断的参考指标;IVIG组和CALs组患儿高血清NT-pro BNP或铁蛋白水平,为预测川崎病IVIG无反应和CALs提供依据。

Objective To detect serum interleukin 6( IL-6),N-terminal pro-brain natriuretic peptide( NT-pro BNP) and serum ferritin in acute Kawasaki disease( KD),and explore their values in the diagnosis of KD,and further to explore the relationship with intravenous immunoglobulin( IVIG) unresponsiveness and coronary arterial lesions( CALs). Methods Totally 108 patients with KD( 81 IVIG responders and 27 IVIG non-responders,31 with CALs and 77 non-CALs) were recruited from October 2014 to February 2016 at Department of Pediatrics of Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology,64 were boys and 44 were girls. Their ages ranged from 2 months to 11 years and 5 months. A total of 30 children with respiratory tract infection were selected as the control group,18 were boys and 12 were girls,ages ranged from 4 months to 10 years. Serum IL-6,NT-pro BNP and serum ferritin were measured at the day of admission. The differences between groups were analyzed by t-test. To compare the power of serum level of interleukin 6( IL-6),N-terminal pro-brain natriuretic peptide( NT-pro BNP) and serum ferritin levels in predicting KD,IVIG unresponsiveness and CALs,receiver-operating characteristic( ROC) curves were plotted and areas under the curve( AUC)were calculated. All data are presented as means ± standard deviation. Results( 1) The levels of IL-6 135 ± 268 ng/L,NT-pro BNP 1008 ± 1675 ng/L and ferritin 227 ± 238μg/L were significantly higher in the acute phase patients with KD than those of the control group 27 ± 29 ng/L for IL-6( t = 2. 192,P = 0. 03),109 ± 100 ng/L for NT-pro BNP( t = 5. 463,P = 0. 000) and 72 ± 101μg/L for ferritin( t = 3. 437,P = 0. 001).( 2) The levels of NT-pro BNP 1837 ± 2666 ng/L in IVIG unresponsive group were significantly higher than those of the IVIG responsive group 720 ± 1032 ng/L( t = 3. 108,P = 0. 002). However,there were no significant difference of IL-6 and serum ferritin between the two groups.( 3) The levels of NT-pro BNP inCALs group 1703 ± 2569 ng/L vs 742 ± 1080 ng/L,serum ferritin340 ± 405μg/L vs 183 ± 99μg/L were significantly higher than those of the non-CALs group( P < 0. 05). However,there was no significant difference of IL-6 between the two groups.( 4) The area under the curve for predicting KD with various variables were as follows:serum IL-6 0. 773,NT-pro BNP 0. 835 and serum ferritin 0. 793. The area under the curve for predicting resistance to IVIG with serum NT-pro BNP was 0. 623. The area under the curve for predicting CALs with various variables were as follows: NT-pro BNP 0. 612 and ferritin 0. 671. The ROC of ferritin for predicting CALs is better than NT-pro BNP. A ferritin cut-off value of 160. 2μg/L yielded a sensitivity of 73. 7%,specificity of 52. 1%. Conclusion The serum IL-6,NT-pro BNP and serum ferritin can be used as useful parameters in early diagnosis of KD. Elevated NT-pro BNP or serum ferritin may be useful to predict IVIG resistance and CALs in KD patients.