Bhattacharya Baishali, Carlsten James, Sabo Edmond, Kethu Sripathi, Meitner Patricia, Tavares Rosemarie, Jakate Shriram, Mangray Shamlal, Aswad Bassam, Resnick Murray B
Department of Pathology, Rhode Island Hospital, Brown Medical School, Lifespan Academic Center, Providence, RI 02903, USA.
Hum Pathol. 2007 Dec;38(12):1744-53. doi: 10.1016/j.humpath.2007.05.008. Epub 2007 Sep 27.
Differentiating eosinophilic esophagitis from gastroesophageal reflux disease is important given their pathogenetic differences and responses to therapy. Eotaxins are a family of chemokines important for activation and recruitment of eosinophils mediated by their receptor, chemokine receptor-3 (CCR-3). Interleukin 5 (IL-5) is a key cytokine involved in many steps of eosinophil production and recruitment. The aim of this study was to compare the messenger RNA expression of the eotaxins, CCR-3, and IL-5 between well-characterized groups of patients with eosinophilic esophagitis, patients with gastroesophageal reflux disease, and healthy individuals. This was a retrospective study using esophageal biopsies from 33 patients with eosinophilic esophagitis, 20 patients with gastroesophageal reflux disease, and 17 healthy controls. Parameters studied included demographic features, presenting symptoms, endoscopic findings, histopathologic features, and messenger RNA levels of eotaxins 1, 2, and 3, CCR-3, and IL-5 by quantitative real-time polymerase chain reaction using formalin-fixed, paraffin-embedded tissue. Patients with eosinophilic esophagitis were predominantly males (M/F=3:1), with a mean age of 15.9 years and a mean eosinophil count of 55 per x400 high-power field. Patients with gastroesophageal reflux disease had a mean age of 31.5 years and a mean eosinophil count of 5.8 per high-power field. Total intraepithelial eosinophil and lymphocyte counts, the presence of superficial eosinophil clusters, microabscesses, and basal cell hyperplasia were all significantly associated with eosinophilic esophagitis as opposed to gastroesophageal reflux disease (P<.0001). The mean expression levels of eotaxin-3 were markedly elevated in patients with eosinophilic esophagitis as compared with the gastroesophageal reflux disease and healthy control groups (731+/-276, 31+/-12, and 1.5+/-0.4 pg/ng beta-actin, respectively; P<.001). Mean expression levels of eotaxins 1 and 2, IL-5, and CCR-3 were also significantly increased in the patients with eosinophilic esophagitis, albeit at lower levels than eotaxin-3. In conclusion, our results highlight the important contribution of eotaxin-3 in the pathogenesis of eosinophilic esophagitis. Determination of eotaxin-3 levels by real-time polymerase chain reaction on paraffinized, formalin-fixed tissue may be a useful test in the differentiation of eosinophilic esophagitis from gastroesophageal reflux disease.
鉴于嗜酸性食管炎与胃食管反流病在发病机制和治疗反应上存在差异，区分二者很重要。嗜酸性粒细胞趋化因子是一类趋化因子，通过其受体趋化因子受体-3（CCR-3）介导，对嗜酸性粒细胞的激活和募集很重要。白细胞介素5（IL-5）是参与嗜酸性粒细胞生成和募集多个步骤的关键细胞因子。本研究的目的是比较嗜酸性食管炎患者、胃食管反流病患者和健康个体这几类特征明确的人群中嗜酸性粒细胞趋化因子、CCR-3和IL-5的信使核糖核酸表达。这是一项回顾性研究，使用了33例嗜酸性食管炎患者、20例胃食管反流病患者和17名健康对照者的食管活检样本。研究参数包括人口统计学特征、出现的症状、内镜检查结果、组织病理学特征，以及使用福尔马林固定、石蜡包埋组织通过定量实时聚合酶链反应检测的嗜酸性粒细胞趋化因子1、2和3、CCR-3和IL-5的信使核糖核酸水平。嗜酸性食管炎患者以男性为主（男/女=3:1），平均年龄15.9岁，每400个高倍视野的嗜酸性粒细胞平均计数为55个。胃食管反流病患者的平均年龄为31.5岁，每高倍视野的嗜酸性粒细胞平均计数为5.8个。与胃食管反流病相比，总上皮内嗜酸性粒细胞和淋巴细胞计数、浅表嗜酸性粒细胞簇的存在、微脓肿和基底细胞增生均与嗜酸性食管炎显著相关（P<0.0001）。与胃食管反流病和健康对照组相比，嗜酸性食管炎患者中嗜酸性粒细胞趋化因子-3的平均表达水平显著升高（分别为731±276、31±12和1.5±0.4 pg/ng β-肌动蛋白；P<0.001）。嗜酸性食管炎患者中嗜酸性粒细胞趋化因子1和2、IL-5和CCR-3的平均表达水平也显著升高，尽管低于嗜酸性粒细胞趋化因子-3的水平。总之，我们的结果突出了嗜酸性粒细胞趋化因子-3在嗜酸性食管炎发病机制中的重要作用。通过对石蜡包埋、福尔马林固定组织进行实时聚合酶链反应测定嗜酸性粒细胞趋化因子-3水平，可能是区分嗜酸性食管炎与胃食管反流病的一项有用检测。
