Gudjonsdottir Johanna, Roth Bodil, Ohlsson Bodil, Hagander Lars, Salö Martin
Department of Clinical Sciences in Lund, Pediatrics, Lund University, Lasarettsgatan 48, 221 85, Lund, Sweden.
Department of Surgery, Skåne University Hospital, Malmö, Sweden.
Pediatr Surg Int. 2025 Apr 10;41(1):112. doi: 10.1007/s00383-025-06008-8.
Leucine rich alpha-2 glycoprotein 1 (LRG1) has emerged as a promising biomarker for appendicitis, especially in pediatric patients. However, the currently available data are sparse, and the biomarker must be validated in more settings and compared to standard inflammatory markers. We aimed to evaluate the diagnostic and discriminative utility of serum and urine LRG1 in children with other causes of abdominal pain (no appendicitis) versus appendicitis, and uncomplicated versus complicated appendicitis.
The study design was prospective including children ≤ 15 years with suspected appendicitis. Blood and urine samples were collected at the time of clinical evaluation at the Pediatric Emergency Department and analyzed for concentrations of LRG1. Appendicitis diagnosis and severity were determined through histopathological examination and intraoperative findings. Group comparisons were carried out using Kruskal-Wallis test with post hoc Dunn-Bonferroni tests for pairwise comparisons. Associations between LRG1 and other laboratory and clinical variables and the odds of appendicitis and complicated appendicitis were assessed by univariate and multivariable logistic regression analyses. Diagnostic (no appendicitis versus appendicitis) and discriminative (uncomplicated versus complicated appendicitis) performance were evaluated through Receiver Operating Characteristic (ROC) curves with analyses of Areas Under the Curve (AUC). Optimal cutoffs were generated using Youden's index, and diagnostic and predictive values were calculated and compared.
172 children were included. 132 (77%) had appendicitis and 56 (42%) of these had complicated appendicitis. The median age was 10 (IQR 8-12) years and 98 (57%) were boys. Serum concentrations of LRG1 did not differ significantly between the groups. Urine LRG1 was significantly higher among children with complicated appendicitis and no appendicitis compared to children with uncomplicated appendicitis (p < 0.001). In the logistic regression analysis of all children with suspected appendicitis, increased serum LRG1 was associated with a decreased odds of appendicitis (OR 0.96 [95% CI 0.93-0.99], p = 0.008). This association remained after adjustment for age, sex and symptom duration (aOR 0.95 [0.92-0.98], p = 0.003). Urine LRG1 was not associated with the odds of appendicitis. Neither serum nor urine LRG 1 were significantly associated with the odds of complicated appendicitis. When it comes to diagnosing appendicitis, both serum and urine LRG1 had AUC values of 0.39. However, urine LRG had a specificity of 95% and a PPV of 83%. The discriminative performance of serum LRG1 was poor, but the AUC for urine LRG1 of 0.65 was better than the ones for leukocytes, neutrophils and neutrophil percentages. Still, it was lower than the AUCs for C-reactive protein (CRP) and Appendicitis Inflammatory Response (AIR) score. Urine LRG1 has a high specificity and PPV for all cases of appendicitis, and correctly identifies cases of complicated appendicitis to a greater extent than some of the currently available inflammatory markers. Still, the regression analyses show no significant associations between urine LRG1 and appendicitis and complicated appendicitis in children.
In contrast to previous studies, in this cohort serum LRG1 was associated with decreased odds of appendicitis, shedding some doubt over the clinical utilization of serum LRG1 as a biomarker for appendicitis in children.
富含亮氨酸的α-2糖蛋白1（LRG1）已成为阑尾炎颇具前景的生物标志物，尤其是在儿科患者中。然而，目前可用的数据稀少，该生物标志物必须在更多情况下进行验证，并与标准炎症标志物进行比较。我们旨在评估血清和尿液LRG1在腹痛由其他原因引起（非阑尾炎）的儿童与阑尾炎儿童，以及单纯性阑尾炎与复杂性阑尾炎儿童中的诊断和鉴别效用。
本研究设计为前瞻性研究，纳入≤15岁疑似阑尾炎的儿童。在儿科急诊科进行临床评估时采集血液和尿液样本，并分析LRG1浓度。通过组织病理学检查和术中发现确定阑尾炎的诊断和严重程度。采用Kruskal-Wallis检验进行组间比较，并使用事后Dunn-Bonferroni检验进行两两比较。通过单变量和多变量逻辑回归分析评估LRG1与其他实验室及临床变量之间的关联，以及阑尾炎和复杂性阑尾炎的几率。通过绘制受试者工作特征（ROC）曲线并分析曲线下面积（AUC）来评估诊断（非阑尾炎与阑尾炎）和鉴别（单纯性阑尾炎与复杂性阑尾炎）性能。使用约登指数生成最佳截断值，并计算和比较诊断及预测值。
共纳入172名儿童。132名（77%）患有阑尾炎，其中56名（42%）为复杂性阑尾炎。中位年龄为10岁（四分位间距8 - 12岁），98名（57%）为男孩。各组间血清LRG1浓度无显著差异。与单纯性阑尾炎儿童相比，复杂性阑尾炎和非阑尾炎儿童的尿液LRG1显著更高（p < 0.001）。在对所有疑似阑尾炎儿童的逻辑回归分析中，血清LRG1升高与阑尾炎几率降低相关（比值比0.96 [95%置信区间0.93 - 0.99]，p = 0.008）。在对年龄、性别和症状持续时间进行调整后，这种关联仍然存在（校正后比值比0.95 [0.92 - 0.98]，p = 0.003）。尿液LRG1与阑尾炎几率无关。血清和尿液LRG1均与复杂性阑尾炎几率无显著关联。在诊断阑尾炎方面，血清和尿液LRG1的AUC值均为0.39。然而，尿液LRG的特异性为95%，阳性预测值为83%。血清LRG1的鉴别性能较差，但尿液LRG1的AUC为0.65，优于白细胞、中性粒细胞及中性粒细胞百分比的AUC。不过，它低于C反应蛋白（CRP）和阑尾炎炎症反应（AIR）评分 的AUC。尿液LRG1对所有阑尾炎病例具有高特异性和阳性预测值，并且在更大程度上能够正确识别复杂性阑尾炎病例，优于一些目前可用的炎症标志物。尽管如此，回归分析显示儿童尿液LRG1与阑尾炎及复杂性阑尾炎之间无显著关联。
与先前研究不同，在本队列中血清LRG1与阑尾炎几率降低相关，这对血清LRG1作为儿童阑尾炎生物标志物的临床应用产生了一些质疑。
