花生口服免疫治疗后，嗜碱性粒细胞对 Ara h 2 的敏感性早期下降先于持续无反应。
Early decrease in basophil sensitivity to Ara h 2 precedes sustained unresponsiveness after peanut oral immunotherapy.
机构信息
Food Allergy Center, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, Mass; Food Allergy Science Initiative at Broad Institute at Massachusetts Institute of Technology and Harvard, Boston, Mass.
Food Allergy Center, Massachusetts General Hospital, Boston, Mass.
出版信息
J Allergy Clin Immunol. 2019 Nov;144(5):1310-1319.e4. doi: 10.1016/j.jaci.2019.07.028. Epub 2019 Aug 1.
BACKGROUND
Only some patients with peanut allergy undergoing oral immunotherapy (OIT) achieve sustained clinical response. Basophil activation could provide a functional surrogate of efficacy.
OBJECTIVE
We hypothesized that changes in basophil sensitivity and area under the curve (AUC) to the immunodominant allergen Ara h 2 correlate with clinical responses to OIT.
METHODS
Children with peanut allergy aged 7 to 13 years were enrolled in a single-center, open-label peanut OIT trial. Levels of specific immunoglobulins were measured throughout OIT. Peripheral blood from multiple time points was stimulated in vitro with peanut allergens for flow cytometric assessment of the percentage of CD63 activated basophils.
RESULTS
Twenty-two of 30 subjects were successfully treated with OIT; after avoidance, 9 achieved sustained unresponsiveness (SU), and 13 had transient desensitization (TD). Basophil sensitivity, measured by using the dose that induces 50% of the maximal basophil response, to Ara h 2 stimulation decreased from baseline in subjects with SU (after OIT, P = .0041; after avoidance, P = .0011). At 3 months of OIT, basophil sensitivity in subjects with SU decreased from baseline compared with that in subjects with TD (median, 18-fold vs 3-fold; P = .01), with a receiver operating characteristic of 0.84 and optimal fold change of 4.9. Basophil AUC to Ara h 2 was suppressed after OIT equally in subjects with SU and those with TD (P = .4). After avoidance, basophil AUC rebounded in subjects with TD but not those with SU (P < .001). Passively sensitized basophils suppressed with postavoidance SU plasma had a lower AUC than TD plasma (6.4% vs 38.9%, P = .03).
CONCLUSIONS
Early decreases in basophil sensitivity to Ara h 2 correlate with SU. Basophil AUC rebounds after avoidance in subjects with TD. Therefore, different aspects of basophil activation might be useful for monitoring of OIT efficacy.
背景
只有部分接受口服免疫治疗（OIT）的花生过敏患者能获得持续的临床缓解。嗜碱性粒细胞激活可作为疗效的替代指标。
目的
我们假设花生过敏原 Ara h 2 诱导的嗜碱性粒细胞敏感性和曲线下面积（AUC）的变化与 OIT 的临床反应相关。
方法
招募了 7 至 13 岁的花生过敏儿童，进行了一项单中心、开放标签的花生 OIT 试验。在 OIT 过程中全程测量特异性免疫球蛋白水平。使用花生过敏原体外刺激多个时间点的外周血，通过流式细胞术评估 CD63 激活的嗜碱性粒细胞的百分比。
结果
30 名受试者中有 22 名成功接受 OIT 治疗；回避后，9 名获得持续无反应（SU），13 名获得短暂脱敏（TD）。SU 患者 Ara h 2 刺激的嗜碱性粒细胞敏感性（以诱导最大嗜碱性粒细胞反应 50%的剂量表示）从基线下降（OIT 后，P=0.0041；回避后，P=0.0011）。在 OIT 治疗 3 个月时，SU 患者的嗜碱性粒细胞敏感性与 TD 患者相比从基线下降（中位数，18 倍与 3 倍；P=0.01），ROC 为 0.84，最佳倍数变化为 4.9。SU 和 TD 患者的 Ara h 2 AUC 在 OIT 后均受到抑制（P=0.4）。回避后，TD 患者的嗜碱性粒细胞 AUC 反弹，但 SU 患者没有（P<0.001）。在 SU 后被动致敏的嗜碱性粒细胞对 TD 血浆的抑制作用较低（6.4%比 38.9%，P=0.03）。
结论
Ara h 2 诱导的嗜碱性粒细胞敏感性早期下降与 SU 相关。TD 患者在回避后嗜碱性粒细胞 AUC 反弹。因此，嗜碱性粒细胞激活的不同方面可能有助于监测 OIT 的疗效。
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