Fundora Jennifer B, Zhu Jie, Yanek Lisa R, Go Mitzi, Shakeel Fauzia, Brooks Sandra S, Yang Jun, Hackam David J, Everett Allen D, Shores Darla R
Department of Pediatrics, Division of Neonatology, Johns Hopkins University School of Medicine, 1800 Orleans St, Suite 8534, Baltimore, MD, 21287, USA.
Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Ave. Ross Building 1129, Baltimore, MD, 21205, USA.
Dig Dis Sci. 2022 Mar;67(3):863-871. doi: 10.1007/s10620-021-06929-z. Epub 2021 Mar 18.
Neonates are at risk of gastrointestinal emergencies including necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP). Identifying biomarkers to aid in diagnosis is imperative. We hypothesized that circulating intestinal-specific protein concentrations would distinguish infants with intestinal injury from controls.
To identify serum concentrations of intestinal-specific protein(s) in infants with intestinal injury and controls.
We used an in silico approach to identify intestinal-specific proteins. We collected serum from control infants and infants with NEC or SIP and measured protein concentrations using ELISA. If baseline concentrations were near the detection limit in initial control assays, we proceeded to assess concentrations in a larger cohort of controls and infants with injury. Control infants were frequency matched to infants with injury and compared with nonparametric and mixed-effects models analysis.
We evaluated four proteins with high intestinal expression: Galectin-4 (Gal-4), S100G, Trefoil Factor-3, and alanyl aminopeptidase. Only Gal-4 demonstrated consistent results near the lower limit of quantification in controls and was studied in the larger cohorts. Gal-4 concentration was low in 111 control infants (median 0.012 ng/ml). By contrast, Gal-4 was significantly increased at diagnosis in infants with surgical NEC and SIP (n = 14, p ≤ 0.001 and n = 8, p = 0.031) compared to matched controls, but not in infants with medical NEC (n = 32, p = 0.10).
Of the intestinal-specific proteins evaluated, circulating Gal-4 concentrations were at the assay detection limit in control infants. Gal-4 concentrations were significantly elevated in infants with surgical NEC or SIP, suggesting that Gal-4 may serve as a biomarker for neonatal intestinal injury.
新生儿面临包括坏死性小肠结肠炎（NEC）和自发性肠穿孔（SIP）在内的胃肠道急症风险。识别有助于诊断的生物标志物至关重要。我们假设循环中肠道特异性蛋白浓度可区分肠道损伤婴儿与对照组。
确定肠道损伤婴儿和对照组中肠道特异性蛋白的血清浓度。
我们采用计算机方法识别肠道特异性蛋白。我们收集了对照组婴儿以及患有NEC或SIP的婴儿的血清，并使用酶联免疫吸附测定法（ELISA）测量蛋白浓度。如果在初始对照试验中基线浓度接近检测限，我们接着评估更大一组对照组和损伤婴儿的浓度。将对照婴儿与损伤婴儿进行频率匹配，并通过非参数和混合效应模型分析进行比较。
我们评估了四种肠道高表达蛋白：半乳糖凝集素-4（Gal-4）、S100G、三叶因子-3和丙氨酰氨基肽酶。只有Gal-4在对照组中在定量下限附近显示出一致的结果，并在更大的队列中进行了研究。111名对照婴儿的Gal-4浓度较低（中位数为0.012纳克/毫升）。相比之下，与匹配的对照组相比，患有外科NEC和SIP的婴儿在诊断时Gal-4显著升高（分别为n = 14，p≤0.001和n = 8，p = 0.031），但患有内科NEC的婴儿（n = 32，p = 0.10）则未升高。
在所评估的肠道特异性蛋白中，对照婴儿的循环Gal-4浓度处于检测限。患有外科NEC或SIP的婴儿Gal-4浓度显著升高，表明Gal-4可能作为新生儿肠道损伤的生物标志物。
