Gunaydin Nursen Cigerci, Azarsiz Elif, Susluer Sunde Yilmaz, Kutukculer Necil, Gunduz Cumhur, Gulen Figen, Aksu Guzide, Tanac Remziye, Demir Esen
Faculty of Medicine, Division of Pediatric Allergy and Immunology, Department of Pediatrics, Namık Kemal University, Tekirdag, Turkey.
Department of Pediatric Allergy and Immunology, Faculty of Medicine, Ege University, Izmir, Turkey.
Ann Allergy Asthma Immunol. 2022 Dec;129(6):751-757.e3. doi: 10.1016/j.anai.2022.07.022. Epub 2022 Jul 30.
Oral immunotherapy (OIT) is a novel allergen-specific treatment for food allergies.
To investigate the effect of OIT on blocking antibodies, T cell regulation, and cytokine response during immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) treatment.
A total of 59 children with IgE-mediated CMA who were followed in pediatric allergy outpatient clinic and 18 healthy children were included. The children were evaluated in the following 4 groups: OIT group, elimination group (patients receiving dairy elimination diet), tolerance group (patients who developed tolerance), and healthy control group. Milk-specific IgE, IgG4, and IgA levels, cow's milk induration diameters in skin prick test, CD4 + CD25 + FoxP3 + Treg cell percentages, messenger RNA (mRNA) expressions, and interleukin (IL)-10, transforming growth factor-beta (TGF-β), IL-2, IL-4, and IL-13 cytokine levels were compared between the groups.
The mean age of the patients was 42.6 ± 39 (6-201) months, and 63.6% (n = 49) of the patients were girls. We observed an increase in total IgE levels (P = .02), a decrease in cow's milk sIgE (P = .08, NS), and an increase in cow's milk component (β-lactoglobulin and casein) specific IgA (P < .05) and IgG4 (P < .001) levels at 2 months after the maintenance phase of OIT. In addition, the immune response after OIT treatment, which had a 100% clinical success rate, was notable for similar CD4 + CD25 + FoxP3 + cell percentages (P = .8), and increased IL-10 (P = .04) levels and increased but statistically nonsignificant TGF-β levels (P = .17) compared with those before treatment. FoxP3 mRNA expression was similar to that of patients who developed natural tolerance. Pretreatment and post-treatment FoxP3 mRNA-FoxP3 flow cytometric expressions were positively correlated with TGF-β concentrations in the OIT group.
A successful immune response to OIT was found, possibly through the blockage of IgE-mediated allergen presentation by blocking antibodies, marked IL-10 cytokine response, and TGF-β response. FoxP3 mRNA expression was similar to the natural tolerance mechanism, but more studies are needed.
口服免疫疗法（OIT）是一种针对食物过敏的新型过敏原特异性治疗方法。
研究口服免疫疗法在免疫球蛋白（Ig）E介导的牛奶过敏（CMA）治疗过程中对阻断抗体、T细胞调节和细胞因子反应的影响。
纳入59例在儿科过敏门诊接受随访的IgE介导的CMA患儿和18例健康儿童。将这些儿童分为以下4组进行评估：口服免疫疗法组、排除组（接受乳制品排除饮食的患者）、耐受组（已产生耐受的患者）和健康对照组。比较各组之间的牛奶特异性IgE、IgG4和IgA水平、皮肤点刺试验中牛奶硬结直径、CD4 + CD25 + FoxP3 +调节性T细胞百分比、信使核糖核酸（mRNA）表达以及白细胞介素（IL）-10、转化生长因子-β（TGF-β）、IL-2、IL-4和IL-13细胞因子水平。
患者的平均年龄为42.6±39（6 - 201）个月，63.6%（n = 49）的患者为女孩。我们观察到在口服免疫疗法维持期后2个月，总IgE水平升高（P = 0.02），牛奶特异性IgE降低（P = 0.08，无统计学意义），牛奶成分（β-乳球蛋白和酪蛋白）特异性IgA（P < 0.05）和IgG4（P < 0.001）水平升高。此外，口服免疫疗法治疗后的免疫反应临床成功率为100%，其显著特点是CD4 + CD25 + FoxP3 +细胞百分比相似（P = 0.8），IL-10水平升高（P = 0.04），TGF-β水平升高但无统计学意义（P = 0.17），与治疗前相比。FoxP3 mRNA表达与自然产生耐受的患者相似。口服免疫疗法组治疗前和治疗后FoxP3 mRNA - FoxP3流式细胞术表达与TGF-β浓度呈正相关。
发现口服免疫疗法有成功的免疫反应，可能是通过阻断抗体阻断IgE介导的过敏原呈递、显著的IL-10细胞因子反应和TGF-β反应实现的。FoxP3 mRNA表达与自然耐受机制相似，但仍需要更多研究。
