Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Eosinophilic Gastrointestinal Diseases Program, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Allergy. 2021 Dec;76(12):3755-3765. doi: 10.1111/all.14874. Epub 2021 May 10.
Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil-associated proteins to diagnose EoE and predict esophageal eosinophilia.
Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein-1 (MBP-1), galectin-10 (CLC/GAL-10), Eotaxin-2 and Eotaxin-3, and urine osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed.
Of 183 specimens were collected from 56 EoE patients and 15 non-EoE controls with symptoms of esophageal dysfunction; 33 EoE patients had paired pre- and post-treatment specimens. Plasma (CLC/GAL-10, ECP, EDN, Eotaxin-3, MBP-1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL-10, Eotaxin-3, ECP, EDN, MBP-1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL-10, ECP, and MBP-1 were significantly decreased in patients with esophageal eosinophil counts <15/hpf in response to treatment. AEC, CLC/GAL-10, ECP, EDN, OPN, and MBP-1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment, and atopy; AEC combined with MBP-1 best predicted the counts.
We identified novel panels of eosinophil-associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from controls and predicting esophageal eosinophil counts.
食管组织学对于嗜酸性食管炎（EoE）的诊断和疾病活动监测至关重要。但目前尚未发现经过验证的非侵入性生物标志物。本研究旨在确定血液和尿液中嗜酸性粒细胞相关蛋白在诊断 EoE 和预测食管嗜酸性粒细胞浸润方面的作用。
收集行内镜活检的患儿的血液和尿液标本。检测绝对嗜酸性粒细胞计数（AEC）、血浆嗜酸性粒细胞衍生神经毒素（EDN）、嗜酸性粒细胞阳离子蛋白（ECP）、主要碱性蛋白-1（MBP-1）、半乳糖凝集素-10（CLC/GAL-10）、嗜酸性粒细胞趋化因子-2（Eotaxin-2）和嗜酸性粒细胞趋化因子-3（Eotaxin-3）、尿液骨桥蛋白（OPN）和基质金属蛋白酶-9（MMP-9）的水平。评估 EoE 与对照组之间以及治疗前后的差异，并评估预测 EoE 诊断和食管嗜酸性粒细胞计数的能力。
共纳入 56 例 EoE 患儿和 15 例有食管功能障碍症状但无 EoE 的对照组患儿的 183 份标本，其中 33 例 EoE 患儿具有治疗前后配对标本。与对照组相比，EoE 患儿的血浆（CLC/GAL-10、ECP、EDN、Eotaxin-3、MBP-1）和尿液（OPN）生物标志物均升高。与单独的 AEC 相比，包含 CLC/GAL-10、Eotaxin-3、ECP、EDN、MBP-1 和 AEC 的组合在区分 EoE 与对照组方面更具优势。在治疗后食管嗜酸性粒细胞计数<15/hpf 的患者中，AEC、CLC/GAL-10、ECP 和 MBP-1 显著降低。AEC、CLC/GAL-10、ECP、EDN、OPN 和 MBP-1 均能利用混合模型控制年龄、性别、治疗和特应性来预测食管嗜酸性粒细胞计数；AEC 联合 MBP-1 可最佳预测计数。
本研究确定了新的嗜酸性粒细胞相关蛋白组合，与单独的 AEC 相比，这些组合在区分 EoE 与对照组和预测食管嗜酸性粒细胞计数方面更具优势。
