Changes of immune and inflammation related indexes in children with Kawasaki disease at acute stageand their relationships with prognosis
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摘要:目的 分析川崎病（KD）患儿急性期中性粒细胞表面CD64、生长分化因子-15（GDF15）、血清淀粉样蛋白A（SAA）变化及其与预后的关系。方法 回顾性分析本院105例急性期KD患儿临床资料（KD组），并选取同期入院体检的110例健康儿童作为对照组。KD组患儿入院后均经免疫球蛋白（IVIG）治疗，比较KD组与对照组外周血中性粒细胞表面CD64、GDF-15、SAA水平差异。以发病3个月后冠状动脉损伤（CAL）情况为依据，将患儿分为CAL组和非CAL组，比较2组治疗前外周血中性粒细胞表面CD64、GDF-15、SAA水平。采用受试者工作特征（ROC）曲线评估上述指标对KD患儿CAL发生的预测价值。结果 KD组治疗后外周血中性粒细胞表面CD64、GDF-15、SAA水平均较治疗前降低，且KD组治疗前后上述指标水平均高于对照组，差异有统计学意义（P < 0.05）。KD组发病初期CAL发生率及严重程度均高于发病3个月后，差异有统计学意义（P < 0.05）。CAL组（n=31）治疗前外周血中性粒细胞表面CD64、GDF-15、SAA水平均高于非CAL组（n=74），差异有统计学意义（P < 0.05）。ROC曲线分析发现，治疗前外周血中性粒细胞表面CD64、GDF-15、SAA水平对KD患儿CAL均具有较高预测价值[曲线下面积（AUC）=0.632、0.846、0.775，P < 0.05]，其截断值为78.60%、1 655.39 ng/mL、795.41 mg/L，且3项联合检测的预后预测价值最高（AUC=0.908，P < 0.05）。结论 中性粒细胞表面CD64、GDF-15、SAA可能参与KD急性期病情进展，治疗前水平能预测KD患儿发病3个月后CAL情况。Abstract:Objective To analyze the changes of CD64 on the surface of neutrophils, growth differentiation factor-15 (GDF-15) and serum amyloid A (SAA) in children with Kawasaki disease (KD) at acute phase and their relationships with prognosis.Methods The clinical materials of 105 children with KD at acute phase (KD group) in authors'hospital were retrospectively analyzed, and 110 healthy children with physical examination in the same period were selected as control group. Children in the KD group were treated with immunoglobulin (IVIG) after admission, and the levels of CD64 on the surface of neutrophils in the peripheral blood, GDF-15 and SAA were compared between the KD group and the control group. According to the condition of coronary artery lesions (CAL) at 3 months after onset, the children were divided into CAL group and non-CAL group, and the levels of CD64 on the surface of neutrophils in the peripheral blood, GDF-15 and SAA were compared between the two groups before treatment. Receiver operating characteristic (ROC) curve was used to evaluate the value of the above indicators in predicting the occurrence of CAL in children with KD.Results After treatment, the levels of CD64 on the surface of neutrophils in the peripheral blood, GDF-15 and SAA in the KD group were significantly lower than those before treatment, and the levels of above indicators before and after treatment in the KD group were significantly higher than those in the control group (P < 0.05). In the KD group, the incidence rate and severity of CAL at the early onset were significantly higher than those at 3 months after onset (P < 0.05). The levels of CD64 on the surface of neutrophils in the peripheral blood, GDF-15 and SAA before treatment in the CAL group (n=31) were significantly higher than those in the non-CAL group (n=74) (P < 0.05). ROC curve analysis showed that the levels of CD64 on the surface of neutrophils in the peripheral blood, GDF-15 and SAA before treatment had high predictive values for CAL in children with KD[area under the curve (AUC)=0.632, 0.846, 0.775, P < 0.05], and their cut-off values were 78.60%, 1 655.39 ng/mL and 795.41 mg/L, and the combination of the three indexes had the highest predictive values for prognosis (AUC=0.908, P < 0.05).Conclusion The CD64 on the surface of neutrophils, GDF-15 and SAA may be involved in the progression of KD at acute phase, and their levels before treatment can predict incidence of CAL in children with KD at 3 months after onset.
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Keywords:
- Kawasaki disease /
- acute phase /
- neutrophils /
- CD64 /
- growth differentiation factor-15 /
- serum amyloid A /
- coronary artery
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表 1 KD组与对照组外周血中性粒细胞表面CD64、GDF-15、SAA水平比较(x±s)
组别 中性粒细胞表面CD64/% GDF-15/(ng/mL) SAA/(mg/L) KD组(n=105) 治疗前 70.73±14.70*# 1 690.47±377.99*# 750.03±153.62*# 治疗后 34.22±7.39* 991.36±204.68* 258.46±51.28* 对照组(n=110) 16.15±3.24 469.63±101.25 3.54±0.61 KD: 川崎病; GDF-15: 生长分化因子-15; SAA: 血清淀粉样蛋白A。与对照组比较, *P < 0.05; 与治疗后比较, #P < 0.05。 
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表 2 KD组发病初期及发病3个月后CAL发生情况[n(%)]
时间 n 0级 Ⅰ级 Ⅱ级 合计 发病初期 105 41(39.05) 58(55.24) 6(5.71) 64(60.95) 发病3个月后 105 74(70.48)* 29(27.62)* 2(1.91)* 31(29.52)* 与发病初期比较, *P < 0.05。
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表 3 CAL组与非CAL组外周血中性粒细胞表面CD64、GDF-15、SAA水平比较(x±s)
组别 n 中性粒细胞表面CD64/% GDF-15/(ng/mL) SAA/(mg/L) CAL组 31 75.61±15.92 2 007.31±326.73 847.01±123.61 非CAL组 74 68.69±13.77* 1 557.74±314.94* 709.40±147.22* CAL: 冠状动脉损伤; GDF-15: 生长分化因子-15; SAA: 血清淀粉样蛋白A。与CAL组比较, *P < 0.05。
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表 4 治疗前外周血中性粒细胞表面CD64、GDF-15、SAA及联合检测预测KD患儿发生CAL的价值
指标 截断值 灵敏度/% 特异度/% 约登指数 AUC 95% CI CD64 78.60% 54.84 78.38 0.332 0.632 0.504~0.761 GDF-15 1 655.39 ng/mL 90.32 64.86 0.552 0.846 0.773~0.919 SAA 795.41 mg/L 70.97 78.38 0.494 0.775 0.675~0.875 3项联合 — 83.90 89.20 0.731 0.908 0.842~0.975
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