Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Department of Pediatrics, UNC Food Allergy Initiative, University of North Carolina, Chapel Hill, North Carolina, USA.
Clin Transl Gastroenterol. 2019 Dec;10(12):e00099. doi: 10.14309/ctg.0000000000000099.
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.
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).
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).
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.
由于目前的过敏测试缺乏准确性，因此对于治疗嗜酸性食管炎（EoE），饮食排除法的应用受到限制。我们旨在开发一种免疫方法来识别饮食诱因，并前瞻性地测试过敏原特异性免疫特征指导的饮食排除疗法。
在第一阶段，我们开发并评估了两种方法，用于通过 24 名 EoE 成人的样本确定特定食物的触发因素：外周血 CD4+T 细胞增殖测定和食管活检中食物特异性 IgG4 水平。在第二阶段，我们在接受 6 周治疗的前瞻性队列中对这些方法制定的饮食消除方案进行了临床测试（NCT02722148）。结果包括峰值嗜酸性粒细胞计数（eos/hpf）、内镜检查结果（通过 EoE 内镜参考评分测量）和症状（通过 EoE 症状活动指数测量）。
通过两种检测方法中的任意一种阳性检测，优化参数，从而分别产生花生、鸡蛋、大豆、小麦和牛奶的预测和已知触发物之间的 60%、75%、53%、58%和 53%的一致性。在临床测试中，基于检测的消除食物的平均数量为 3.4，22 名受试者中有 19 名符合治疗要求。治疗后，中位数峰值嗜酸性粒细胞计数从 75 降至 35（P = 0.007）；有 4 名组织学应答者（21%）。治疗后 EoE 内镜参考评分和 EoE 症状活动指数评分也降低（4.6 降至 3.0；P = 0.002；32.5 降至 25.0；P = 0.06）。
我们成功地使用 CD4 T 细胞增殖和食管食物特异性 IgG4 水平开发了一种新的测试方法，具有较高的准确率。在临床测试中，这导致嗜酸性粒细胞计数、内镜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。
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