原标题:持续成功的花生口服免疫治疗与低嗜碱性粒细胞活化以及花生特异性IgE低相关
——浙大迪迅 译
①口服免疫治疗(OIT)可以成功地使许多花生过敏患者脱敏,但中断治疗或低剂量维持时,随着时间的推移,临床耐受性会降低。因此,为了提高这种治疗的有效性和可持续性,我们试图寻找生物标志物和临床工具来预测治疗结果和监测治疗应答。②我们评估了全血中嗜碱性粒细胞的活化程度和花生特异性免疫球蛋白的血浆水平是否是花生OIT的有用的生物标志物③我们在一项大规模的、单点、双盲、随机、安慰剂对照、II期花生OIT研究中,纵向测定了OIT前、OIT中、OIT后全血中嗜碱性粒细胞对花生过敏原蛋白刺激的体外活化情况,以及花生特异性IgE和IgG4。我们在花生口服激发试验有临床反应的患者和花生口服耐受者之间比较嗜碱性粒细胞的反应性和花生特异性免疫球蛋白水平。④花生OIT显著降低了嗜碱性粒细胞活化程度以及花生、Ara h1、Ara h2和Ara h3特异性IgE,还有sIgE/总IgE,但sIgG4/sIgE升高了。积极的OIT后13周对4 g花生产生反应的受试者在体外表现出更高的花生诱导的嗜碱性粒细胞活化和更高的花生特异性IgE和sIgE/总IgE,以及较低的sIgG4/sIgE。值得注意的是,入组时嗜碱性粒细胞应答较低的参与者更有可能获得治疗成功。花生OIT后需要大量抑制嗜碱性细胞的活化才能维持长期的临床耐受性。⑤评估花生特异性嗜碱性粒细胞活化情况和花生特异性免疫球蛋白水平可以帮助预测治疗结果,并区分OIT后的短暂脱敏和持续无反应。
延伸阅读
JACI
[IF:13.1]
Sustained Successful Peanut Oral Immunotherapy Associated with Low Basophil Activation and Peanut-Specific IgE
https://doi.org/10.1016/j.jaci.2019.10.038
Abstract
Background
Oral immunotherapy (OIT) can successfully desensitize many peanut allergic subjects, but clinical tolerance diminishes over time upon discontinuation, or low dose maintenance, of peanut. Therefore, in order to improve the efficacy and sustainability of such therapy, we sought to identify biomarkers and clinical tools that can predict therapeutic outcomes and monitor treatment responses.
Objective
We evaluated whether basophil activation in whole blood, and plasma levels of peanut-specific immunoglobulins, are useful biomarkers for peanut OIT.
Methods
We longitudinally measured, before, during and after OIT, basophil activation in whole blood ex vivo in response to peanut stimulation, and peanut-specific IgE and IgG4, in a large, single-site, double-blind, randomized, placebo-controlled, phase 2 peanut OIT study. We compared basophil responsiveness and peanut specific immunoglobulins between those who were clinically reactive vs. tolerant to peanut oral challenges.
Results
Peanut OIT significantly decreased basophil activation, peanut-specific, Ara h 1, Ara h 2 and Ara h 3 IgEs, and sIgE/total IgE, but increased sIgG4/sIgE. Participants who became reactive to 4 g of peanut 13 weeks off active OIT exhibited higher peanut-induced basophil activation ex vivo and higher peanut-specific IgEs and sIgE/total IgE, but lower sIgG4/sIgE. Notably, participants entering the study with low basophil responsiveness were more likely to achieve treatment success. Substantial suppression of basophil activation was required to maintain long-term clinical tolerance after peanut OIT.
Conclusion
Assessments of peanut-specific basophil activation and peanut-specific immunoglobulins can help to predict treatment outcomes, and to differentiate transient desensitization vs. sustained unresponsiveness after OIT.
All Author:
Mindy Tsai DMSc KaoriMukaiPhD R. SharonChinthrajahMD Kari C.NadeauMD, PhD Stephen J.GalliMD
2019-12- 10 Article
创建过敏性疾病的科研、科普知识交流平台,为过敏患者提供专业诊断、治疗、预防的共享平台。