Mabrouk Randa R, Amer Hanaa A, Soliman Dina A, Mohamed Nesrine A, El-Ghoneimy Dalia H, Hamdy Ahmed M, Atef Sara A
Department of Clinical Pathology & Immunology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Department of Pediatrics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Egypt J Immunol. 2019 Jan;26(1):15-29.
Cow's milk allergy (CMA) is known to be either IgE- or non-IgE mediated. Regulatory T (Treg) cell defect is involved in the pathogenesis of both types. Vitamin D has been suggested to improve the generation of allergen-specific Treg cell populations with the potential to provide safe and long-term alleviation of disease symptoms. This study aimed to assess Vitamin D status in children with physician-diagnosed CMA and to investigate the effect of in vitro cultivation with Vitamin D on the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells following in vitro stimulation of cells with cow's milk allergen in culture. This cross-sectional study included 20 children with CMA and 20 healthy age and sex-matched children as a control group. All patients were subjected to clinical evaluation, cow's milk skin prick test (SPT), cow's milk elimination and oral re-challenge test in patients with negative cow's milk SPT and in those with gastrointestinal presentation, measurement of serum Vitamin D level and assessment of the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells in response to stimulation with cow's milk allergen extract with and without Vitamin D in culture. Vitamin D deficiency was detected in 80% of children with CMA. Percentage of Foxp3+ and IL10+ co-expression on Treg cells was significantly increased after stimulation with cow's milk allergen extract in the presence of Vitamin D. A significant positive correlation was observed between serum Vitamin D level and percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells as well as level of Foxp3+ and IL10+ co-expression on Treg cells at baseline (control cultures without stimulation) and after PBMCs stimulation with cow's milk allergen extract in the presence of Vitamin D. Re-stimulation with cow's milk allergen extract was performed in vitro in order to evaluate milk-induced immune stimulation and regulation. In conclusion, patients with CMA whether IgE- or non-IgE mediated had Vitamin D deficiency with a decreased number of CD4+CD25highFoxp3+IL10+ Treg cells which increased after in vitro addition of Vitamin D with increased Foxp3 and IL10 co-expression.
已知牛奶过敏（CMA）是由IgE介导或非IgE介导的。调节性T（Treg）细胞缺陷参与了这两种类型的发病机制。有人提出维生素D可改善过敏原特异性Treg细胞群体的生成，有可能安全、长期地缓解疾病症状。本研究旨在评估经医生诊断为CMA的儿童的维生素D状态，并研究在培养基中用维生素D进行体外培养对用牛奶过敏原刺激细胞后抗原驱动的CD4+CD25highFoxp3+IL10+ Treg细胞百分比的影响。这项横断面研究包括20名患有CMA的儿童和20名年龄、性别匹配的健康儿童作为对照组。所有患者均接受临床评估、牛奶皮肤点刺试验（SPT）、牛奶回避以及牛奶SPT阴性和有胃肠道症状患者的口服激发试验、血清维生素D水平测定，以及评估在培养基中添加和不添加维生素D的情况下，用牛奶过敏原提取物刺激后抗原驱动的CD4+CD25highFoxp3+IL10+ Treg细胞的百分比。80%的CMA儿童被检测出维生素D缺乏。在用牛奶过敏原提取物刺激且存在维生素D的情况下，Treg细胞上Foxp3+和IL10+共表达的百分比显著增加。在基线时（未刺激的对照培养物）以及在用牛奶过敏原提取物刺激外周血单核细胞（PBMCs）且存在维生素D的情况下，血清维生素D水平与抗原驱动的CD4+CD25highFoxp3+IL10+ Treg细胞百分比以及Treg细胞上Foxp3+和IL10+共表达水平之间观察到显著正相关。为了评估牛奶诱导的免疫刺激和调节作用，在体外进行了牛奶过敏原提取物的再刺激。总之，无论是IgE介导还是非IgE介导的CMA患者都存在维生素D缺乏，CD4+CD25highFoxp3+IL10+ Treg细胞数量减少，在体外添加维生素D后数量增加，同时Foxp3和IL10共表达增加。
