Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD, USA.
J Allergy Clin Immunol. 2012 Nov;130(5):1123-1129.e2. doi: 10.1016/j.jaci.2012.05.039. Epub 2012 Jul 15.
Monoclonal antibodies directed at IgE demonstrate clinical efficacy in subjects with peanut allergy, but previous studies have not addressed the kinetics of the clinical response or the role of mast cells and basophils in the food-induced allergic response.
We sought to determine the kinetics of the clinical response to omalizumab and whether clinical improvement is associated with either mast cell or basophil suppression.
Subjects with peanut allergy were treated with omalizumab for 6 months and assessed for clinical and cellular responses. At baseline, subjects had a double-blind, placebo-controlled oral food challenge (OFC), skin prick test titration (SPTT), and basophil histamine release (BHR) to peanut. BHR was repeated at week 2 and then weekly until it decreased to less than 20% of baseline values. The OFCs and SPTTs were repeated after the BHR reduction (or at week 8 if BHR did not decrease) and again at 6 months.
Fourteen subjects enrolled in the study. At the second food challenge, there was a significant increase in the threshold dose of peanut inducing allergic symptoms (80 to 6500 mg, P < .01). Peanut-induced BHR was either completely suppressed (n = 5) or 10-fold more allergen was required to induce maximal BHR (n = 9), and SPTT responses were not significantly changed from baseline. After 6 months of omalizumab, further changes in the OFC threshold dose or BHR were not observed, but a significant suppression in SPTTs was identified.
The clinical response to omalizumab occurs early in treatment when the basophil, but not the mast cell, is suppressed, supporting a role for the basophil in acute food reactions.
针对 IgE 的单克隆抗体在花生过敏患者中显示出临床疗效,但以前的研究并未解决临床反应的动力学或肥大细胞和嗜碱性粒细胞在食物诱导的过敏反应中的作用。
我们旨在确定奥马珠单抗治疗的临床反应动力学,以及临床改善是否与肥大细胞或嗜碱性粒细胞抑制有关。
花生过敏患者接受奥马珠单抗治疗 6 个月,并评估临床和细胞反应。在基线时,患者进行了双盲、安慰剂对照的口服食物挑战(OFC)、皮肤点刺试验滴定(SPTT)和花生的嗜碱性粒细胞组胺释放(BHR)。在第 2 周和每周重复 BHR,直到其降至基线值的 20%以下。在 BHR 降低后(或如果 BHR 没有降低则在第 8 周)重复 OFC 和 SPTT,然后在 6 个月时再次重复。
14 名患者入组研究。在第二次食物挑战时,引起过敏症状的花生阈值剂量显着增加(80 至 6500mg,P<.01)。花生诱导的 BHR 要么完全被抑制(n=5),要么需要 10 倍的过敏原才能诱导最大 BHR(n=9),并且 SPTT 反应与基线相比没有显着变化。在奥马珠单抗治疗 6 个月后,OFC 阈值剂量或 BHR 没有进一步变化,但 SPTT 明显抑制。
奥马珠单抗的临床反应在治疗早期发生,此时嗜碱性粒细胞而非肥大细胞被抑制,支持嗜碱性粒细胞在急性食物反应中的作用。