Wright B L, Ochkur S I, Olson N S, Shim K P, Jacobsen E A, Rank M A, Dellon E S, Lee J J
Division of Allergy, Asthma and Clinical Immunology, Department of Medicine.
Division of Pulmonology, Department of Pediatrics, Phoenix Children's Hospital, Phoenix, Arizona.
Dis Esophagus. 2018 Feb 1;31(2). doi: 10.1093/dote/dox139.
Eosinophil peroxidase is an eosinophil-specific, cytoplasmic protein stored in the secondary granules of eosinophils. While eosinophil peroxidase deposition is increased in the esophagus in eosinophilic esophagitis (EOE), its potential role as a peripheral marker is unknown. This study aims to examine the relationship between serum eosinophil peroxidase and esophageal eosinophilia in eosinophilic esophagitis. Prospectively collected serum from 19 subjects with incident EoE prior to treatment and 20 non-EoE controls were tested for serum eosinophil peroxidase, eosinophilic cationic protein, and eosinophil derived neurotoxin using ELISA. Matching esophageal tissue sections were stained and assessed for eosinophil peroxidase deposition using a histopathologic scoring algorithm. Mean peripheral blood absolute eosinophil counts in eosinophilic esophagitis subjects were significantly elevated compared to controls (363 vs. 195 cells/μL, P = 0.008). Absolute median serum eosinophil peroxidase, eosinophil cationic protein, and eosinophil derived neurotoxin did not differ between groups; however, when normalized for absolute eosinophil counts, eosinophilic esophagitis subjects had significantly lower median eosinophil peroxidase levels (2.56 vs. 6.96 ng/mL per eos/μL, P = 0.002, AUC 0.79 (0.64, 0.94 95% CI)). Multivariate analysis demonstrated this relationship persisted after controlling for atopy. Esophageal biopsies from eosinophilic esophagitis subjects demonstrated marked eosinophil peroxidase deposition (median score 46 vs. 0, P < 0.0001). Normalized eosinophil peroxidase levels inversely correlated with esophageal eosinophil density (r = -0.41, P = 0.009). In contrast to marked tissue eosinophil degranulation, circulating eosinophils appear to retain their granule proteins in EoE. Investigations of normalized serum eosinophil peroxidase levels as a biomarker of EoE are ongoing.
嗜酸性粒细胞过氧化物酶是一种嗜酸性粒细胞特异性的胞质蛋白，储存于嗜酸性粒细胞的次级颗粒中。虽然在嗜酸性粒细胞性食管炎（EOE）患者的食管中，嗜酸性粒细胞过氧化物酶沉积增加，但其作为外周标志物的潜在作用尚不清楚。本研究旨在探讨嗜酸性粒细胞性食管炎患者血清嗜酸性粒细胞过氧化物酶与食管嗜酸性粒细胞增多之间的关系。前瞻性收集了19例治疗前新发EOE患者和20例非EOE对照者的血清，采用酶联免疫吸附测定法（ELISA）检测血清嗜酸性粒细胞过氧化物酶、嗜酸性粒细胞阳离子蛋白和嗜酸性粒细胞衍生神经毒素。对匹配的食管组织切片进行染色，并使用组织病理学评分算法评估嗜酸性粒细胞过氧化物酶沉积情况。与对照组相比，嗜酸性粒细胞性食管炎患者外周血嗜酸性粒细胞绝对计数显著升高（363对195个细胞/μL，P = 0.008）。两组间血清嗜酸性粒细胞过氧化物酶、嗜酸性粒细胞阳离子蛋白和嗜酸性粒细胞衍生神经毒素的绝对中位数无差异；然而，以嗜酸性粒细胞绝对计数进行标准化后，嗜酸性粒细胞性食管炎患者的嗜酸性粒细胞过氧化物酶中位数水平显著更低（2.56对6.96 ng/mL每嗜酸性粒细胞/μL，P = 0.002，曲线下面积0.79（0.64，0.94 95%可信区间））。多变量分析表明，在控制特应性后，这种关系仍然存在。嗜酸性粒细胞性食管炎患者的食管活检显示有明显的嗜酸性粒细胞过氧化物酶沉积（中位数评分46对0，P < 0.0001）。标准化的嗜酸性粒细胞过氧化物酶水平与食管嗜酸性粒细胞密度呈负相关（r = -0.41，P = 0.009）。与明显的组织嗜酸性粒细胞脱颗粒相反，在EOE中循环嗜酸性粒细胞似乎保留了其颗粒蛋白。将标准化血清嗜酸性粒细胞过氧化物酶水平作为EOE生物标志物的研究正在进行中。
