OBJECTIVES Dietary elimination for treatment of eosinophilic esophagitis (EoE) is limited by lack of accuracy in current allergy tests. We aimed to develop an immunologic approach to identify dietary triggers and prospectively test allergen-specific immune signature-guided dietary elimination therapy. METHODS In the first phase, we developed and assessed 2 methods for determining selected food triggers using samples from 24 adults with EoE: a CD4+ T-cell proliferation assay in peripheral blood and food-specific tissue IgG4 levels in esophageal biopsies. In the second phase, we clinically tested elimination diets created from these methods in a prospective cohort treated for 6 weeks (NCT02722148). Outcomes included peak eosinophil counts (eos/hpf), endoscopic findings (measured by the EoE Endoscopic Reference Score), and symptoms (measured by the EoE Symptom Activity Index). RESULTS Parameters were optimized with a positive test on either assay, yielding agreements of 60%, 75%, 53%, 58%, and 53% between predicted and known triggers of peanut, egg, soy, wheat, and milk, respectively. In clinical testing, the mean number of foods eliminated based on the assays was 3.4, and 19 of 22 subjects were compliant with treatment. After treatment, median peak eosinophil counts decreased from 75 to 35 (P = 0.007); there were 4 histologic responders (21%). The EoE Endoscopic Reference Score and EoE Symptom Activity Index score also decreased after treatment (4.6 vs 3.0; P = 0.002; and 32.5 vs 25.0; P = 0.06, respectively). DISCUSSION We successfully developed a new testing approach using CD4 T-cell proliferation and esophageal food-specific IgG4 levels, with promising accuracy rates. In clinical testing, this led to improvement in eosinophil counts, endoscopic severity, and symptoms of dysphagia, but a smaller than expected number of patients achieved histologic remission.

中文翻译：

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一种新的过敏原特异性免疫特征导向的嗜酸性食管炎饮食消除方法。

目的 用于治疗嗜酸性食管炎 (EoE) 的饮食消除受到当前过敏测试缺乏准确性的限制。我们旨在开发一种免疫学方法来识别饮食触发因素并前瞻性地测试过敏原特异性免疫特征引导的饮食消除疗法。方法 在第一阶段，我们使用来自 24 名患有 EoE 的成年人的样本开发和评估了 2 种确定选定食物触发因素的方法：外周血中的 CD4+ T 细胞增殖测定和食道活检中的食物特异性组织 IgG4 水平。在第二阶段，我们在一个治疗 6 周的前瞻性队列（NCT02722148）中对通过这些方法创建的消除饮食进行了临床测试。结果包括峰值嗜酸性粒细胞计数 (eos/hpf)、内窥镜检查结果（通过 EoE 内窥镜参考评分测量）、和症状（由 EoE 症状活动指数衡量）。结果 参数通过任一测定的阳性测试进行优化，花生、鸡蛋、大豆、小麦和牛奶的预测触发因素和已知触发因素之间的一致性分别为 60%、75%、53%、58% 和 53%。在临床测试中，基于检测的平均消除食物数量为 3.4，22 名受试者中有 19 名符合治疗要求。治疗后，嗜酸性粒细胞峰值计数中位数从 75 降至 35（P = 0.007）；有 4 名组织学应答者 (21%)。EoE 内窥镜参考评分和 EoE 症状活动指数评分在治疗后也有所下降（分别为 4.6 对 3.0；P = 0.002；和 32.5 对 25.0；P = 0.06）。讨论 我们成功开发了一种使用 CD4 T 细胞增殖和食道食物特异性 IgG4 水平的新检测方法，有希望的准确率。在临床试验中，这导致嗜酸性粒细胞计数、内镜检查严重程度和吞咽困难症状的改善，但达到组织学缓解的患者数量少于预期。