Zhou Xiaoying, Dunham Diane, Sindher Sayantani B, Long Andrew, Fernandes Andrea, Chang Iris, Assa'ad Amal, Pongracic Jacqueline, Spergel Jonathan M, Tam Jonathan, Tilles Stephen, Wang Julie, Boyd Scott D, Chinthrajah R Sharon, Nadeau Kari C
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California, USA.
Allergy. 2025 Mar;80(3):762-774. doi: 10.1111/all.16311. Epub 2024 Sep 18.
Omalizumab (XOLAIR®)-assisted multi-food oral immunotherapy (mOIT) has been shown to safely, effectively, and rapidly desensitize patients with multiple food allergies. In our clinical trial (NCT02626611) on omalizumab-assisted mOIT, different desensitization outcomes (success or failure of desensitization) were observed following a period of either continued or discontinued mOIT. However, the association between the immunological changes induced by omalizumab-assisted mOIT and desensitization outcomes has not yet been fully elucidated. In this study, due to the key roles of regulatory T (Treg) cells and the type 2 helper T cell (Th2) pathway in immune tolerance to food allergens, we aimed to characterize their association with the desensitization outcomes of omalizumab-assisted mOIT.
Mass cytometry and multiplex cytokine assays were performed on blood samples obtained from participants with allergies to peanut, cashew, or milk in our phase 2 clinical study (NCT02626611). Comprehensive statistical and bioinformatic analyses were conducted on high-dimensional cytometry-based single-cell data and high-throughput multiplex cytokine data.
Our results demonstrated that the frequency of HLA-DR Treg cells, and the production of Th2 cytokines (IL-4, IL-5, IL-13, and IL-9) as well as the immunoregulatory cytokine IL-10 by peripheral blood mononuclear cells (PBMCs) was significantly increased in cultures with allergen compared to cultures with media alone at baseline (Week 0). We also observed increased frequency of allergen responsive HLA-DR Treg cells and enhanced production of IL-10 by PBMCs in participants who achieved successful desensitization compared to those with failure of desensitization. However, the production of Th2 cytokines by PBMCs did not show significant differences between participants with different desensitization outcomes (success vs. failure of desensitization), despite omalizumab-assisted mOIT inducing a significant reduction in the production of Th2 cytokines.
We demonstrated that the frequency of HLA-DR Treg cells and IL-10 cytokine production by PBMCs are associated with desensitization outcomes of omalizumab-assisted mOIT. These findings suggest potential immunological parameters that could be targeted to enhance desensitization success rates.
奥马珠单抗（XOLAIR®）辅助的多食物口服免疫疗法（mOIT）已被证明能安全、有效且迅速地使多种食物过敏患者脱敏。在我们关于奥马珠单抗辅助mOIT的临床试验（NCT02626611）中，在持续或中断mOIT一段时间后，观察到了不同的脱敏结果（脱敏成功或失败）。然而，奥马珠单抗辅助mOIT诱导的免疫变化与脱敏结果之间的关联尚未完全阐明。在本研究中，由于调节性T（Treg）细胞和2型辅助性T细胞（Th2）途径在食物过敏原免疫耐受中的关键作用，我们旨在表征它们与奥马珠单抗辅助mOIT脱敏结果的关联。
在我们的2期临床研究（NCT02626611）中，对花生、腰果或牛奶过敏的参与者的血样进行了质谱流式细胞术和多重细胞因子检测。对基于高维流式细胞术的单细胞数据和高通量多重细胞因子数据进行了全面的统计和生物信息学分析。
我们的结果表明，与仅含培养基的培养物相比，在基线（第0周）时，含有过敏原的培养物中HLA-DR Treg细胞的频率、外周血单核细胞（PBMC）产生的Th2细胞因子（IL-4、IL-5、IL-13和IL-9）以及免疫调节细胞因子IL-10均显著增加。我们还观察到，与脱敏失败的参与者相比，脱敏成功的参与者中过敏原反应性HLA-DR Treg细胞的频率增加，PBMC产生的IL-10增强。然而，尽管奥马珠单抗辅助mOIT导致Th2细胞因子的产生显著减少，但不同脱敏结果（脱敏成功与失败）的参与者之间PBMC产生的Th2细胞因子没有显示出显著差异。
我们证明了PBMC中HLA-DR Treg细胞的频率和IL-10细胞因子的产生与奥马珠单抗辅助mOIT的脱敏结果相关。这些发现提示了可能有助于提高脱敏成功率的潜在免疫参数。
