原標(biāo)題：持續(xù)成功的花生口服免疫治療與低嗜堿性粒細(xì)胞活化以及花生特異性IgE低相關(guān)
　?、倏诜庖咧委?OIT)可以成功地使許多花生過(guò)敏患者脫敏，但中斷治療或低劑量維持時(shí)，隨著時(shí)間的推移，臨床耐受性會(huì)降低。因此，為了提高這種治療的有效性和可持續(xù)性，我們?cè)噲D尋找生物標(biāo)志物和臨床工具來(lái)預(yù)測(cè)治療結(jié)果和監(jiān)測(cè)治療應(yīng)答。②我們?cè)u(píng)估了全血中嗜堿性粒細(xì)胞的活化程度和花生特異性免疫球蛋白的血漿水平是否是花生OIT的有用的生物標(biāo)志物③我們?cè)谝豁?xiàng)大規(guī)模的、單點(diǎn)、雙盲、隨機(jī)、安慰劑對(duì)照、II期花生OIT研究中，縱向測(cè)定了OIT前、OIT中、OIT后全血中嗜堿性粒細(xì)胞對(duì)花生過(guò)敏原蛋白刺激的體外活化情況，以及花生特異性IgE和IgG4。我們?cè)诨ㄉ诜ぐl(fā)試驗(yàn)有臨床反應(yīng)的患者和花生口服耐受者之間比較嗜堿性粒細(xì)胞的反應(yīng)性和花生特異性免疫球蛋白水平。④花生OIT顯著降低了嗜堿性粒細(xì)胞活化程度以及花生、Ara h1、Ara h2和Ara h3特異性IgE，還有sIgE/總IgE，但sIgG4/sIgE升高了。積極的OIT后13周對(duì)4 g花生產(chǎn)生反應(yīng)的受試者在體外表現(xiàn)出更高的花生誘導(dǎo)的嗜堿性粒細(xì)胞活化和更高的花生特異性IgE和sIgE/總IgE，以及較低的sIgG4/sIgE。值得注意的是，入組時(shí)嗜堿性粒細(xì)胞應(yīng)答較低的參與者更有可能獲得治療成功。花生OIT后需要大量抑制嗜堿性細(xì)胞的活化才能維持長(zhǎng)期的臨床耐受性。⑤評(píng)估花生特異性嗜堿性粒細(xì)胞活化情況和花生特異性免疫球蛋白水平可以幫助預(yù)測(cè)治療結(jié)果，并區(qū)分OIT后的短暫脫敏和持續(xù)無(wú)反應(yīng)。
延伸閱讀
JACI                                            
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
　　創(chuàng)建過(guò)敏性疾病的科研、科普知識(shí)交流平臺(tái)，為過(guò)敏患者提供專(zhuān)業(yè)診斷、治療、預(yù)防的共享平臺(tái)。