Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Sachs' Children and Youth Hospital, Södersjukhuset, Karolinska Institute, Stockholm, Sweden.
Scand J Immunol. 2021 Apr;93(4):e13005. doi: 10.1111/sji.13005. Epub 2020 Dec 15.
Anti-IgE treatments, such as omalizumab, have shown promising effects in allergy treatment. Our previous work has shown that individualized omalizumab treatment (OT) allows a safe initiation and rapid up-dosing of peanut oral immunotherapy (OIT) in peanut-allergic adolescents. However, the broader immunological effects of this OT are incompletely understood. In this pilot study, we longitudinally followed the total B- and T-cell immunity during OT, using flow cytometry, ELISpot and ELISA. Peripheral blood mononuclear cells (PBMCs) and plasma were collected from participants (n = 17) at several timepoints during treatment, before starting OT (baseline), prior to starting OIT during OT (start OIT) and at maintenance dose OIT prior to OT reduction (maintenance). OT did not affect the total B-cell compartment over treatment time, but our results suggest an association between the OT dosage scheme and the B-cell compartment. Further, in vitro polyclonal T-cell activation at the different timepoints suggests a cytokine skewing towards the Th1 phenotype at the expense of Th2- and Th9-related cytokines during treatment. No differences in the frequencies or phenotype of regulatory T cells (Tregs) over treatment time were observed. Finally, plasma chemokine levels were stable over treatment time, but suggest elevated gut homing immune responses in treatment successes during the treatment as compared to treatment failures. The novel and explorative results of this pilot study help to improve our understanding on the immunological effects of OT used to facilitate OIT and provide guidance for future immunological investigation in large clinical trials.
抗 IgE 治疗,如奥马珠单抗,在过敏治疗中显示出有前景的效果。我们之前的工作表明,个体化奥马珠单抗治疗(OT)可安全启动并快速增加花生过敏青少年的口服免疫治疗(OIT)剂量。然而,这种 OT 的更广泛的免疫作用仍不完全清楚。在这项初步研究中,我们使用流式细胞术、ELISpot 和 ELISA 对 OT 期间的总 B 细胞和 T 细胞免疫进行了纵向随访。在治疗过程中,从参与者(n=17)的几个时间点收集外周血单核细胞(PBMC)和血浆,在开始 OT 之前(基线)、OT 期间开始 OIT 之前(开始 OIT)和 OT 减少前维持剂量 OIT 时(维持)。OT 并没有影响治疗期间的总 B 细胞群,但我们的结果表明 OT 剂量方案与 B 细胞群之间存在关联。此外,不同时间点的多克隆 T 细胞体外激活表明,在治疗过程中,细胞因子向 Th1 表型倾斜,而 Th2 和 Th9 相关细胞因子的数量减少。在治疗期间,T 调节细胞(Tregs)的频率或表型没有变化。最后,血浆趋化因子水平在治疗期间保持稳定,但治疗成功的患者在治疗期间比治疗失败的患者表现出更高的肠道归巢免疫反应。这项初步研究的新颖和探索性结果有助于我们更好地了解 OT 用于促进 OIT 的免疫作用,并为未来的大型临床试验中的免疫学研究提供指导。