Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge.
Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge.
复制标题
使用鼻内猫过敏原激发，奥马珠单抗对嗜碱性粒细胞和肥大细胞反应的影响。
DOI：
10.1016/j.jaci.2009.09.012
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发表时间：
2010-04
影响因子：
14.2
通讯作者：
Saini, Sarbjit S.
中科院分区：
文献类型：
--
作者：
Eckman, John A.;Sterba, Patricia M.;Kelly, Denise;Alexander, Val;Liu, Mark C.;Bochner, Bruce S.;MacGlashan, Donald W., Jr.;Saini, Sarbjit S.
关键词：
奥马珠单抗治疗抑制FcεRI在血液嗜碱性粒细胞上的表达快于皮肤肥大细胞。我们利用奥马珠单抗来阐明鼻过敏原激发（NAC）模型中嗜碱性粒细胞与肥大细胞FcεRI活化的相对贡献。18名猫过敏受试者入组了一项为期3.5个月、双盲、随机（3.5：1）、安慰剂对照的奥马珠单抗标准给药试验。在基线时，受试者接受NAC，灌洗用于PGD 2测量、皮肤点刺试验滴定（SPTT）和血样采集用于嗜碱性粒细胞组胺释放（BHR）和嗜碱性粒细胞IgE/FcεRI测量。在第3天重复嗜碱性粒细胞研究，然后每周重复一次，直到猫过敏原诱导的BHR <基线的20%或直到第45天。在BHR降低后（研究中期NAC）和治疗期结束时（最终NAC）重复基线访视程序。完成所有NAC的奥马珠单抗治疗受试者（n=12）显示，与基线相比，研究中期NAC时最佳猫过敏原剂量的BHR平均值显著降低（降低74%，p=0.001）。此外，相对于基线NAC，这些受试者显示研究中期NAC的平均合并鼻部症状评分（降低50%，p=0.007）和总喷嚏计数（降低59%，p=0.01）显著降低。相比之下，肥大细胞反应（SPTT和鼻灌洗液PGD 2）的测量值仅在最后一次NAC时显著降低。安慰剂组受试者（n=4）未发生嗜碱性粒细胞、NAC症状或肥大细胞指标的变化。当嗜碱性粒细胞（而非肥大细胞）对奥马珠单抗的反应降低时，鼻部症状评分降低，表明嗜碱性粒细胞在急性NAC反应中发挥作用。
Omalizumab treatment suppresses FcεRI expression faster on blood basophils than skin mast cells. We utilized omalizumab to elucidate the relative contributions of basophil versus mast cell FcεRI activation in a nasal allergen challenge (NAC) model. Eighteen cat-allergic subjects were enrolled in a 3.5-month, double-blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing. At baseline, subjects underwent NAC with lavage for PGD2 measurement, skin prick test titration (SPTT), and blood sampling for basophil histamine release (BHR) and basophil IgE/FcεRI measurements. Basophil studies were repeated at day 3 and then weekly until cat allergen-induced BHR was <20% of baseline or until day 45. Baseline visit procedures were repeated after the BHR reduction (mid-study NAC) and at the treatment period’s completion (final NAC). Subjects treated with omalizumab who completed all NACs (n=12) demonstrated significant mean reduction in BHR to an optimal dose of cat allergen by mid-study NAC as compared to baseline (74% decrease, p=0.001). In addition, these subjects demonstrated significant decreases in mean combined nasal symptom scores (50% decrease, p=0.007) and total sneeze counts (59% decrease, p=0.01) by mid-study NAC relative to baseline NAC. In contrast, measures of mast cell response (SPTT and nasal lavage PGD2) were only significantly reduced by the final NAC. Subjects on placebo (n=4) did not experience a shift in basophil, NAC symptom, or mast cell measures. Reduction in nasal symptom scores occurred when the basophil, but not mast cell, response was reduced on omalizumab, implicating a role for basophils in the acute NAC response.
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影响因子：
14.2
作者：
Ong, YE;Menzies-Gow, A;Kay, AB
通讯作者：
Kay, AB
影响因子：
14.2
作者：
Saini, SS;Richardson, JJ;MacGlashan, DW
通讯作者：
MacGlashan, DW
影响因子：
14.2
作者：
Vonakis, Becky M.;Vasagar, Kavitha;Saini, Sarbjit S.
通讯作者：
Saini, Sarbjit S.
影响因子：
24.3
作者：
Hanf, G;Noga, O;Kunkel, G
通讯作者：
Kunkel, G
影响因子：
14.2
作者：
PROUD, D;BAILEY, GS;TOGIAS, AG
通讯作者：
TOGIAS, AG