Division of Allergy and Immunology, Center for Pediatric Eosinophilic Disorders, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Institute for Immunology and Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA, USA.
Allergy. 2021 Nov;76(11):3470-3478. doi: 10.1111/all.14854. Epub 2021 May 14.
Eosinophilic esophagitis (EoE) is a T-cell-mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE-causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen-specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE.
We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E-mediated milk allergy (n = 9). We measured total and milk-specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4 T helper (T ) cell proliferation and cytokine production after stimulation with endotoxin-depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches.
Total and milk-specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused T lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL-4 of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects. Milk-dependent memory T -cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL-4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy.
Peripheral markers of allergen-specific immune activation may be useful in identifying EoE-causal foods. Assaying milk-dependent IL-4 production by circulating memory T lymphocytes most accurately predicts clinical EoE milk allergy.
嗜酸性食管炎（EoE）是一种由特定食物引起的 T 细胞介导的疾病，导致食管功能障碍。现有的过敏测试方式在试图确定 EoE 因果食物时并不有用，需要进行经验性食物消除和反复进行内镜检查。本研究的目的是确定并比较可以以微创方式检测的过敏原特异性免疫特征，以预测 EoE 中的临床食物过敏。
我们从对照受试者（n=17）、有临床 EoE 牛奶过敏的受试者（n=17）和有免疫球蛋白 E 介导的牛奶过敏的受试者（n=9）中获得了血液样本。我们测量了总血浆和牛奶特异性 IgG4 水平以及外周记忆 CD4 T 辅助（T）细胞在刺激内毒素耗尽的牛奶蛋白后的增殖和细胞因子产生。计算并比较了不同方法预测临床 EoE 牛奶过敏的敏感性和特异性。
对照受试者和有临床 EoE 牛奶过敏的受试者之间的总血浆和牛奶特异性 IgG4 水平没有显著差异。牛奶蛋白刺激导致有临床 EoE 牛奶过敏的受试者的 T 淋巴细胞增殖更多（%P1 为 38.3±4.6 比 12.7±2.8，p<0.0001），产生更多的 2 型细胞因子（%IL-4 为 33.7±2.8 比 6.9±1.6，p<0.0001）比对照受试者的细胞更多。牛奶依赖性记忆 T 细胞增殖（敏感性和特异性分别为 88%和 82%）和白细胞介素 4（IL-4）产生（敏感性和特异性均为 100%）最能预测临床 EoE 牛奶过敏。
过敏原特异性免疫激活的外周标志物可能有助于识别 EoE 因果食物。检测循环记忆 T 淋巴细胞中牛奶依赖性 IL-4 产生最能准确预测临床 EoE 牛奶过敏。
