川崎病患儿血清细胞因子水平与冠状动脉病变的关系

doi:10.3760/cma.j.cn441417-20240806-01012

摘要/Abstract

摘要：

目的　分析川崎病患儿血清血管内皮生长因子受体2（VEGFR2）、白细胞介素-23（IL-23）、成纤维细胞生长因子-21（FGF-21）水平与冠状动脉病变（CAL）的关系。方法　本研究为横断面研究。选取2020年6月至2024年3月西安市中心医院收治的120例川崎病患儿为川崎病组，男67例，女53例，年龄（2.88±0.94）岁。根据川崎病患儿是否合并CAL再分为合并CAL组（CAL亚组）52例和未合并CAL组（NCAL亚组）68例。另选择同期健康体检儿童120例为对照组，男69例，女51例，年龄（3.13±1.40）岁。所有确诊为川崎病的患儿均接受标准化治疗，包括高剂量静脉注射免疫球蛋白（IVIg）和阿司匹林。IVIg剂量为2 g/kg，一次性输注。口服阿司匹林，初始剂量为30～50 mg^-1·kg^-1·d^-1，待患儿退热后减至3～5 mg^-1·kg^-1·d^-1。阿司匹林持续治疗8周。收集各组临床资料，检测所有研究对象的血清VEGFR2、IL-23、FGF-21水平，并进行多因素logistic回归分析评估其与CAL的关系。采用受试者操作特征曲线（ROC）分析VEGFR2、IL-23、FGF-21对川崎病患儿发生CAL的诊断价值。采用t检验、F检验、χ²检验进行统计分析。结果　对照组血清VEGFR2、IL-23、FGF-21水平分别为（313.43±50.14）µg/L、（1.44±0.24）µg/L、（4.39±0.58）µg/L，NCAL亚组上述指标分别为（272.12±49.50）µg/L、（2.23±0.43）µg/L、（4.87±0.76）µg/L，CAL亚组上述指标分别为（230.30±38.94）µg/L、（3.18±0.61）µg/L、（6.13±1.23）µg/L；对照组与NCAL亚组上述指标比较，差异均有统计学意义（t=5.453、13.967、4.516，均P0.05）；NCAL亚组与CAL亚组上述指标比较，差异均有统计学意义（t=5.018、9.560、6.499，均P0.05）。CAL亚组IVIg治疗前热程（患儿开始发热至接受IVIg治疗前的持续天数）长于NCAL亚组［（7.42±2.41）d比（5.78±1.65）d］，差异有统计学意义（t=4.431，P0.05）；CAL亚组IVIg治疗反应无应答（IVIg初次治疗后36 h内体温仍高于38 ℃或在治疗后2周内体温再次升高，并伴有至少1项川崎病的临床特征）比例高于NCAL亚组［24.08%（12/52）比8.82%（6/68）］，差异有统计学意义（χ²=4.695，P=0.030）。多因素logistic回归分析显示，血清VEGFR2下降以及IL-23、FGF-21升高均是川崎病患儿发生CAL的独立危险因素（均P0.05）。ROC分析显示，VEGFR2、IL-23和FGF-21预测川崎病患儿发生CAL的灵敏度分别为63.5%、88.5%和86.5%，特异度分别为80.9%、80.9%和66.2%，曲线下面积分别为0.745、0.898和0.817。VEGFR2、IL-23和FGF-21联合检测时，灵敏度和特异度分别为92.3%和95.6%，曲线下面积为0.956。结论　血清VEGFR2下降及IL-23、FGF-21升高与川崎病患儿发生CAL显著相关，三者联合检测可作为预测和诊断川崎病患儿发生CAL的有效生物标志物。

关键词:

川崎病, 冠状动脉病变, 血管内皮生长因子受体2, 白细胞介素-23, 成纤维细胞生长因子-21, 儿童

Abstract:

Objective　To analyze the relationships between serum levels of vascular endothelial growth factor receptor 2 (VEGFR2), interleukin-23 (IL-23), and fibroblast growth factor 21 (FGF-21) and coronary artery lesion (CAL) in children with Kawasaki disease (KD). Methods　This was a cross-sectional study. A total of 120 KD children diagnosed and treated in Xi'an Central Hospital from June 2020 to March 2024 were selected as the KD group, including 67 boys and 53 girls, aged (2.88±0.94) years. According to whether the KD children were combined with CAL or not, they were divided into a combined CAL group (CAL subgroup) of 52 cases and a non-combined CAL group (NCAL subgroup) of 68 cases. Another 120 healthy children [69 boys and 51 girls, aged (3.13±1.40) years] were selected as the control group. All children diagnosed with KD received standardized treatment, including high-dose intravenous immunoglobulin (IVIg) and aspirin. The dose of IVIg was 2 g/kg, a single infusion. The initial dose of aspirin was 30 to 50 mg^-1·kg^-1·d^-1, orally. The dose of aspirin was reduced to 3-5 mg^-1·kg^-1·d^-1 after the fever was reduced. Aspirin treatment continued for 8 weeks. The clinical data of each group were collected, the serum levels of VEGFR2, IL-23, and FGF-21 of all subjects were detected, and their relationships with the occurrence of CAL were evaluated by multivariate logistic regression analysis. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic values of VEGFR2, IL-23, and FGF-21 for the occurrence of CAL in KD children. t test , F test and χ² test were used for statistical analysis. Results　Serum levels of VEGFR2, IL-23, and FGF-21 in the control group were (313.43±50.14) µg/L, (1.44±0.24) µg/L, and (4.39±0.58) µg/L, those in the NCAL subgroup were (272.12±49.50) µg/L, (2.23±0.43) µg/L, and (4.87±0.76) µg/L, and those in the CAL subgroup were (230.30±38.94) µg/L, (3.18±0.61) µg/L, and (6.13±1.23) µg/L. There were statistically significant differences in the above indexes between the control group and the NCAL subgroup (t=5.453, 13.967, and 4.516, all P0.05); there were statistically significant differences in the above indexes between the NCAL subgroup and the CAL subgroup (t=5.018, 9.560, and 6.499, all P0.05). The duration of fever before IVIg treatment in the CAL subgroup was longer than that in the NCAL subgroup [(7.42±2.41) d vs. (5.78±1.65) d], with a statistically significant difference (t=4.431, P0.05). The proportion of non-response to IVIg (body temperature remained above 38 ℃ within 36 h after initial treatment with IVIg or increased again within 2 weeks after treatment, with at least one clinical feature of KD) in the CAL subgroup was higher than that in the NCAL subgroup [24.08% (12/52) vs 8.82% (6/68)], with a statistically significant difference (χ²=4.695, P=0.030). Multivariate logistic regression analysis showed that the decrease of serum VEGFR2 level and the increase of IL-23 and FGF-21 levels were independent risk factors for CAL in KD children (all P0.05). ROC analysis showed that the sensitivities of VEGFR2, IL-23, and FGF-21 to predict the occurrence of CAL in KD children were 63.5%, 88.5%, and 86.5%, the specificities were 80.9%, 80.9%, and 66.2%, and the areas under the curves were 0.745, 0.898, and 0.817. The sensitivity and specificity of VEGFR2, IL-23, and FGF-21 combined detection were 92.3% and 95.6%, and the area under the curve was 0.956. Conclusion　The decrease of serum VEGFR2 level and the increase of serum IL-23 and FGF-21 levels are significantly associated with CAL in KD children, and the combination of these markers can serve as effective biomarkers for predicting and diagnosing CAL in KD children.

Key words:

Kawasaki disease, Coronary artery lesion, Vascular endothelial growth factor receptor 2, Interleukin-23, Fibroblast growth factor 21, , Children

赵兰心田恬高小倩.

川崎病患儿血清细胞因子水平与冠状动脉病变的关系 [J]. 国际医药卫生导报, 2025, 31(1): 55-60.

Zhao Lanxin, Tian Tian, Gao Xiaoqian.

Relationships between levels of serum cytokines and coronary artery lesion in children with Kawasaki disease [J]. International Medicine and Health Guidance News, 2025, 31(1): 55-60.

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