Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Department of Pathology and Laboratory Medicine; University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Dis Esophagus. 2020 Jun 15;33(6). doi: 10.1093/dote/doaa003.
Inflammatory factors in eosinophilic esophagitis (EoE), including major basic protein (MBP), eotaxin-3 (EOT3) and mast cell tryptase (TRP), may predict treatment response to topical corticosteroids (tCS). We aimed to determine whether baseline levels of these markers predict response to tCS for EoE. To do this, we analyzed data from a randomized trial comparing two topical steroids for treatment of newly diagnosed EoE (NCT02019758). A pretreatment esophageal biopsy was stained for MBP, EOT3, and TRP to quantify tissue biomarker levels (cells/mm2). Levels were compared between histologic responders (<15 eos/hpf) and nonresponders (the primary outcome), and endoscopic responders (EREFS<2) and nonresponders. Complete histologic response (<1 eos/hpf) was also assessed, and area under the receiver operator characteristic curve (AUC) was calculated. We also evaluated whether baseline staining predicted symptom relapse in the trial's off-treatment observation phase. Baseline samples were evaluable in 110/111 subjects who completed the randomized trial. MBP levels were higher in nonresponders (n = 36) than responders (704 vs. 373 cells/mm2; P = 0.007), but EOT3 and TRP levels were not statistically different. The combination of all three stains had an AUC of 0.66 to predict response. For complete histologic response, baseline TRP levels were higher in nonresponders (n = 69) than responders (370 vs. 268 mast cells/mm2; P = 0.01), with an AUC of 0.65. The AUC for endoscopic response was 0.68. Baseline staining did not predict symptom recurrence after remission. Pretreatment MBP, EOT3, and TRP levels were not strongly or consistently associated with histologic or endoscopic response to topical steroids. While elevated TRP levels may be associated with nonresponse compared with complete response, the magnitude and predictive utilities were modest. Novel methods for predicting steroid response are still required.
嗜酸性食管炎（EoE）中的炎症因子，包括主要碱性蛋白（MBP）、嗜酸性粒细胞趋化因子-3（EOT3）和肥大细胞胰蛋白酶（TRP），可能预测局部皮质类固醇（tCS）治疗的反应。我们旨在确定这些标志物的基线水平是否可预测 EoE 对 tCS 的反应。为此，我们分析了一项比较两种局部皮质类固醇治疗新诊断的 EoE 的随机试验的数据（NCT02019758）。在治疗前进行食管活检，对 MBP、EOT3 和 TRP 进行染色以定量组织生物标志物水平（细胞/mm2）。比较组织学应答者（<15 个 eos/hpf）和无应答者（主要结局）、内镜应答者（EREFS<2）和无应答者之间的水平。还评估了完全组织学应答（<1 eos/hpf），并计算了接收者操作特征曲线（ROC）下的面积（AUC）。我们还评估了基线染色是否预测试验停药观察期的症状复发。在完成随机试验的 111 名受试者中，有 110 名可评估基线样本。无应答者（n = 36）的 MBP 水平高于应答者（704 与 373 细胞/mm2；P = 0.007），但 EOT3 和 TRP 水平无统计学差异。所有三种染色的组合预测反应的 AUC 为 0.66。对于完全组织学应答，无应答者（n = 69）的基线 TRP 水平高于应答者（370 与 268 肥大细胞/mm2；P = 0.01），AUC 为 0.65。内镜反应的 AUC 为 0.68。基线染色不能预测缓解后症状复发。治疗前 MBP、EOT3 和 TRP 水平与局部皮质类固醇的组织学或内镜反应无强关联或一致性关联。虽然与完全应答相比，升高的 TRP 水平可能与无应答相关，但幅度和预测效用较小。仍需要新的方法来预测类固醇反应。
