急性时相反应蛋白SAA和CRP对川崎病静脉注射免疫球蛋白无应答的预测价值

Predictive value of acute phase proteins SAA and CRP in non-response to intravenous immunoglobulin in Kawasaki disease

目的探讨急性时相反应蛋白血清淀粉样蛋白A(SAA)和C反应蛋白(CRP)对川崎病(KD)患儿静脉注射免疫球蛋白(IVIG)无应答的预测价值。方法根据IVIG无应答的定义将358例KD患儿分为IVIG无应答组(41例)和IVIG应答组(317例)。检测血清中SAA、CRP水平并计算SAA/CRP的值,比较2组患儿IVIG治疗前后的临床和实验室检测指标。二分类Logistic回归分析IVIG无应答的影响因素,通过受试者工作特征(ROC)曲线探讨SAA、CRP对预测IVIG无应答的临床价值。结果IVIG无应答组CRP、SAA、总胆红素、丙氨酸转氨酶和天冬氨酸转氨酶水平高于IVIG应答组(P<0.05),淋巴细胞计数、血小板计数、血清钠和使用IVIG前发热时间低于IVIG应答组(P<0.05)。二分类Logistic回归分析显示,CRP(OR=1.008,95%CI:1.001~1.015)、SAA(OR=1.002,95%CI:1.001~1.003)、总胆红素(OR=1.030,95%CI:1.009~1.051)、血清钠(OR=0.862,95%CI:0.762~0.975)、淋巴细胞计数(OR=0.733,95%CI:0.567~0.947)和IVIG前发热时间(OR=0.688,95%CI:0.513~0.922)是IVIG无应答的独立影响因素(P<0.05)。治疗后,IVIG无应答组冠状动脉病变发生率高于IVIG应答组(P<0.05)。ROC曲线分析显示,SAA和CRP预测IVIG无应答的最佳截断值分别为252.45 mg/L和82.80 mg/L,约登指数分别为0.325和0.382,两者联合预测的约登指数为0.423。SAA、CRP及两者联合预测IVIG无应答的ROC曲线下面积分别为0.681、0.703和0.761,联合预测效能良好。结论急性时相反应蛋白SAA和CRP升高是KD患儿IVIG无应答的危险因素,联合检测可辅助预测IVIG的无应答。

Objective To evaluate the predictive value of acute phase proteins serum amyloid A protein(SAA)and Creactive protein(CRP)for non-response to intravenous immunoglobulin(IVIG)in children with Kawasaki disease(KD).Methods According to the IVIG resistant definition,a total of 358 KD patients were assigned into the IVIG resistant group(n=41)and the IVIG responsive group(n=317).Serum levels of SAA and CRP were tested,and SAA/CRP ratio was calculated.Clinical and laboratory data before and after treatment were compared between the two groups.Binary Logistic regression analysis was used to identify influencing factors for resistance to IVIG.The diagnostic value of SAA and CRP in predicting IVIG resistance in KD was investigated by the receiver operating characteristic(ROC)curve.Results The levels of CRP,SAA,total bilirubin,alanine aminotransferase and asparate aminotransferase were significantly higher in the IVIG resistant group than those of the IVIG responsive group(P<0.05),whereas levels of lymphocyte count,platelet count,serum sodium and duration of fever before IVIG were significantly lower in the IVIG resistant group(P<0.05).The binary Logistic regression analysis showed that CRP(OR=1.008,95%CI:1.001-1.015),SAA(OR=1.002,95%CI:1.001-1.003),total bilirubin(OR=1.030,95%CI:1.009-1.051),serum sodium(OR=0.862,95%CI:0.762-0.975),lymphocyte count(OR=0.733,95%CI:0.567-0.947)and duration of fever before IVIG(OR=0.688,95%CI:0.513-0.922)were the independent influencing factors for IVIG resistance(P<0.05).The incidence of coronary artery lesion was significantly higher after therapy in the IVIG resistant group than that in the IVIG responsive group(P<0.05).ROC curve showed that the Youden index of SAA(cut-off value 252.45 mg/L),CRP(cut-off value 82.80 mg/L)and combined SAA and CRP were 0.325,0.382 and 0.423.The area under the ROC curve of SAA,CRP and two items were 0.681,0.703 and 0.761,respectively.The predictive efficiency of combined application was larger.Conclusion The increased SAA and CRP levels are independent risk factors of IVIG resistance,which can be utilized as combined biomarkers for the prediction of IVIG resistance in KD patients.