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临床指标联合 S100A12/TLR2 信号分子建立川崎病冠状动脉病变新的评分模型。

Clinical indicators combined with S100A12/TLR2 signaling molecules to establish a new scoring model for coronary artery lesions in Kawasaki disease.

机构信息

Department of Rheumatology and Immunology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

出版信息

PLoS One. 2023 Oct 12;18(10):e0292653. doi: 10.1371/journal.pone.0292653. eCollection 2023.

Abstract

Coronary artery lesions (CALs) are the most common and serious complication of Kawasaki disease (KD), and the pathogenesis is unknown. Exploring KD-specific biomarkers and related risk factors is significant for clinical diagnosis and treatment. This study aimed to explore the feasibility of combining clinical indicators with S100A12/TLR2-associated signaling molecules for the predictive modeling of CALs in KD. A total of 346 patients (224 males and 122 females) with KD who visited the rheumatology department of Wuhan Children's Hospital between April 2022 and March 2025 were enrolled and divided into two groups according to the presence or absence of CALS (292 patients had CALs and 54 patients did not). Forty-one variables were collected from the two groups, including demographic characteristics, clinical manifestations, and laboratory data. Single nucleated cells from each patient were extracted, and the expression of the S100A12/TLR2 signal transduction-related molecules S100A12, TLR2, MYD88, and NF-κB were detected by real-time fluorescent quantitative polymerase chain reaction. Statistically significant variables were subjected to logistic regression analysis to determine the independent risk factors for KD with CALs, and a new risk score model was established to assess the predictive efficacy based on receiver operating characteristic curves. Sixteen variables significantly differed between the no-CALs and CALs groups: gender, fever duration, white blood cells (WBC), hemoglobin (HGB), Ce reactive protein (CRP), procalcitonin, serum ferritin (SF), erythrocyte sedimentation rate (ESR), fibrinogen (FIB), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT), serum albumin (ALB), sodium (Na), Interleukin (IL-10), tumor necrosis factor (TNF-α), S100 calcium binding protein A12 (S100A12), and Myeloid Differentiation Factor 88 (MYD88) (p < 0.05). After performing a univariate analysis, 12 variables (gender, fever duration, WBC, HGB, CRP, SF, ESR, FIB, AST/ALT, ALB, Na, and S100A12) were included in the multifactorial binary logistic regression, which showed that fever duration ≥ 6.5 days, ESR ≥ 46.5 mm/h, AST/ALT ≤ 1.51, and S100A12 ≥ 10.02 were independent risk factors for KD with CALs and were assigned scores of 3, 2, 1, and 2, respectively, according to the odds ratio (OR). The total score of each patient was counted, and a new prediction model for KD combined with CALs was established, where < 3.5 was considered low risk and ≥ 3.5 was regarded as high risk; the sensitivity, specificity, Jorden index, and area under the curve of this scoring system were 0.667, 0.836, 0.502, and 0.838, respectively. This new scoring model has good efficacy for predicting the occurrence of KD with CALs. The expression of S100A12 was significantly increased in the CALs group and was an independent risk factor for the occurrence of CALs, and has the potential as a biomarker for predicting KD with CALs.

摘要

冠状动脉病变(CALs)是川崎病(KD)最常见和最严重的并发症,其发病机制尚不清楚。探索 KD 特异性生物标志物和相关危险因素对于临床诊断和治疗具有重要意义。本研究旨在探讨联合临床指标和 S100A12/TLR2 相关信号分子对 KD 患者 CALs 预测建模的可行性。共纳入 2022 年 4 月至 2025 年 3 月期间在武汉儿童医院风湿科就诊的 346 例 KD 患者(男 224 例,女 122 例),根据是否存在 CALs 将其分为两组(292 例存在 CALs,54 例不存在 CALs)。收集两组共 41 个变量,包括人口统计学特征、临床表现和实验室数据。从每位患者中提取单核细胞,通过实时荧光定量聚合酶链反应检测 S100A12/TLR2 信号转导相关分子 S100A12、TLR2、MYD88 和 NF-κB 的表达。对差异有统计学意义的变量进行 logistic 回归分析,确定 KD 合并 CALs 的独立危险因素,并基于受试者工作特征曲线建立新的风险评分模型评估预测效能。无 CALs 组和 CALs 组之间有 16 个变量存在显著差异:性别、发热持续时间、白细胞(WBC)、血红蛋白(HGB)、C 反应蛋白(CRP)、降钙素原、血清铁蛋白(SF)、红细胞沉降率(ESR)、纤维蛋白原(FIB)、天门冬氨酸氨基转移酶-丙氨酸氨基转移酶比值(AST/ALT)、血清白蛋白(ALB)、钠(Na)、白细胞介素(IL-10)、肿瘤坏死因子(TNF-α)、S100 钙结合蛋白 A12(S100A12)和髓样分化因子 88(MYD88)(p<0.05)。进行单因素分析后,12 个变量(性别、发热持续时间、WBC、HGB、CRP、SF、ESR、FIB、AST/ALT、ALB、Na 和 S100A12)纳入多因素二项逻辑回归,结果显示发热持续时间≥6.5 天、ESR≥46.5mm/h、AST/ALT≤1.51 和 S100A12≥10.02 是 KD 合并 CALs 的独立危险因素,其比值比(OR)分别为 3、2、1 和 2,分别赋值 3、2、1 和 2。计算每位患者的总分,建立新的 KD 合并 CALs 预测模型,<3.5 分为低危,≥3.5 分为高危;该评分系统的灵敏度、特异度、约登指数和曲线下面积分别为 0.667、0.836、0.502 和 0.838。该新评分模型对预测 KD 合并 CALs 的发生具有良好的效果。CALs 组 S100A12 表达明显升高,是 CALs 发生的独立危险因素,具有预测 KD 合并 CALs 的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac39/10569519/ba6035563948/pone.0292653.g001.jpg

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