Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cytokine. 2019 Feb;114:26-31. doi: 10.1016/j.cyto.2018.11.025. Epub 2018 Dec 21.
To search the predictive factors of infliximab resistance in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients.
Twenty-seven patients with KD who received infliximab after 4-5 g/kg of IVIG therapy from 2013 to 2015 were consecutively recruited in this study. They were divided into two groups: patients who responded to infliximab (infliximab-responsive group, n = 15) and patients who required additional therapy for the disease control (infliximab-resistant group, n = 12). We analyzed the clinical and laboratory parameters just before the infliximab treatment including serum levels of procalcitonin and cytokines with respect to the infliximab response.
Serum procalcitonin concentration (P = 0.017), neutrophils to lymphocytes ratio (P = 0.013), and % neutrophils (P = 0.004) were higher, and serum sodium concentration (P = 0.017) was lower in infliximab-resistant group than those of infliximab-responsive group, respectively. Multivariate logistic regression analyses indicated that higher procalcitonin concentration (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00-5.00, P = 0.046) and lower sodium levels (OR 0.64, 95% CI 0.32-1.00, P = 0.047), but not other variables, were associated with infliximab-resistance. Serum procalcitonin concentrations positively correlated with the serum levels of interleukin-6, soluble tumor necrosis factor receptor type 1 and type 2, respectively. Analyses of the receiver operating characteristic (ROC) curve showed that the cut-off value of procalcitonin 2.0 ng/ml had 58.3% of sensitivity and 93.3% of specificity. ROC analysis yielded an area under the curve (AUC) of 0.739 to predict infliximab-resistance.
Serum procalcitonin might be an effective biomarker to predict infliximab resistance in severe KD patients who are refractory to IVIG treatment.
探索静脉注射免疫球蛋白（IVIG）耐药性川崎病（KD）患者对英夫利昔单抗耐药的预测因素。
本研究连续纳入 2013 年至 2015 年期间接受英夫利昔单抗治疗的 27 例 KD 患者，这些患者在接受 4-5g/kg IVIG 治疗后接受了英夫利昔单抗治疗。他们被分为两组：对英夫利昔单抗有反应的患者（英夫利昔单抗反应组，n=15）和需要进一步治疗以控制疾病的患者（英夫利昔单抗耐药组，n=12）。我们分析了英夫利昔单抗治疗前的临床和实验室参数，包括降钙素原和细胞因子的血清水平，以评估英夫利昔单抗的反应。
英夫利昔单抗耐药组的血清降钙素原浓度（P=0.017）、中性粒细胞与淋巴细胞比值（P=0.013）和%中性粒细胞（P=0.004）较高，血清钠浓度（P=0.017）较低。多变量逻辑回归分析表明，较高的降钙素原浓度（比值比[OR]1.48，95%置信区间[CI]1.00-5.00，P=0.046）和较低的钠水平（OR 0.64，95%CI 0.32-1.00，P=0.047），但不是其他变量，与英夫利昔单抗耐药有关。血清降钙素原浓度与白细胞介素-6、可溶性肿瘤坏死因子受体 1 和 2 的血清水平呈正相关。受试者工作特征（ROC）曲线分析显示，降钙素原的截断值为 2.0ng/ml 时，其敏感性为 58.3%，特异性为 93.3%。ROC 分析得到预测英夫利昔单抗耐药的曲线下面积（AUC）为 0.739。
血清降钙素原可能是预测对 IVIG 治疗耐药的严重 KD 患者对英夫利昔单抗耐药的有效生物标志物。
