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A pilot study towards the immunological effects of omalizumab treatment used to facilitate oral immunotherapy in peanut‐allergic adolescents
Scandinavian Journal of Immunology ( IF 4.1 ) Pub Date : 2020-11-27 , DOI: 10.1111/sji.13005
Marieke Heiden 1 , Anna Nopp 2, 3 , Josef Brandström 2, 4, 5 , Claudia Carvalho‐Queiroz 1 , Caroline Nilsson 2, 3 , Eva Sverremark‐Ekström 1
Affiliation  

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.

中文翻译:

关于奥马珠单抗治疗可促进花生过敏青少年口服免疫治疗的免疫学作用的初步研究

omalizumab等抗IgE治疗在变态反应治疗中显示出可喜的效果。我们以前的工作表明,个性化的奥马珠单抗治疗(OT)可以使花生过敏青少年安全地开始并快速增加花生口服免疫疗法(OIT)的剂量。但是,这种OT的更广泛的免疫学作用尚未完全了解。在这项前期研究中,我们使用流式细胞仪,ELISpot和ELISA纵向跟踪了OT期间总的B细胞和T细胞免疫力。在治疗期间的几个时间点,开始OT前(基线),在OT期间开始OIT之前(开始OIT)以及在降低OT之前以维持剂量OIT从参与者(n = 17)收集参与者的外周血单核细胞(PBMC)和血浆(n = 17) (维护)。在治疗期间,OT并未影响总的B细胞区室,但是我们的结果表明OT剂量方案与B细胞区室之间存在关联。此外,在不同时间点的体外多克隆T细胞活化表明,在治疗期间,细胞因子向Th1表型倾斜,而Th2和Th9相关的细胞因子却受到了损害。在治疗时间内未观察到调节性T细胞(Tregs)的频率或表型差异。最后,血浆趋化因子水平在治疗时间内是稳定的,但是与治疗失败相比,在治疗成功期间,肠道归巢免疫应答升高。这项先导研究的新颖和探索性结果有助于增进我们对用于促进OIT的OT免疫学作用的理解,并为大型临床试验中的未来免疫学研究提供指导。
更新日期:2020-11-27
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