Takizawa Daigo, Yokooji Tomoharu, Miyamoto Chika, Koga Yuki, Oda Keisuke, Ogino Ryohei, Taogoshi Takanori, Matsuo Hiroaki
Department of Pharmaceutical Services, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Department of Pharmaceutical Services, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Foods. 2025 Apr 21;14(8):1424. doi: 10.3390/foods14081424.
Oral immunotherapy (OIT) is a promising approach for treating food allergy. Here, we elucidated the mechanisms of desensitization induced by OIT in rats sensitized to ovalbumin (OVA). The desensitization was induced by ingestion of OVA three times per week after sensitization in rats. OIT suppressed the decrease in rectal temperature and increase in plasma histamine levels induced by OVA injection immediately and 4 weeks after OIT completion. Plasma OVA-specific IgE (sIgE) levels did not differ between the non-OIT and OIT groups, but OVA-specific IgG levels were higher in the OIT group than in the non-OIT group at both timepoints. To evaluate IgG's effect on IgE crosslinking with OVA, amplified luminescence proximity homogeneous assay involving crosslinking (AlphaCL) was performed. When IgG was removed using a Protein G column, the AlphaCL signal was significantly increased, especially in the OIT group, indicating that OIT-induced IgG inhibited the sIgE response. The proportions of cluster of differentiation (CD)4 cells and CD4CD25FoxP3 cells in mesenteric lymph nodes and spleen were similar between the two groups. These findings indicate that OIT attenuates systemic allergic responses by inhibiting sIgE binding to OVA through increased IgG. Our model is useful for understanding the mechanisms of OIT and optimizing therapeutic strategies for ameliorating food allergies.
口服免疫疗法（OIT）是一种治疗食物过敏的很有前景的方法。在此，我们阐明了卵清蛋白（OVA）致敏大鼠中OIT诱导脱敏的机制。在大鼠致敏后，通过每周三次摄入OVA来诱导脱敏。OIT在OIT完成后即刻及4周时抑制了OVA注射诱导的直肠温度降低和血浆组胺水平升高。非OIT组和OIT组之间的血浆OVA特异性IgE（sIgE）水平无差异，但在两个时间点，OIT组的OVA特异性IgG水平均高于非OIT组。为了评估IgG对IgE与OVA交联的影响，进行了涉及交联的放大发光邻近均相分析（AlphaCL）。当使用蛋白G柱去除IgG时，AlphaCL信号显著增加，尤其是在OIT组，这表明OIT诱导的IgG抑制了sIgE反应。两组肠系膜淋巴结和脾脏中分化簇（CD）4细胞和CD4CD25FoxP3细胞的比例相似。这些发现表明，OIT通过增加IgG抑制sIgE与OVA的结合，从而减轻全身过敏反应。我们的模型有助于理解OIT的机制并优化改善食物过敏的治疗策略。
