Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors
Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors
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DOI：
10.1016/j.jaci.2012.05.038
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发表时间：
2012-11-01
影响因子：
14.2
通讯作者：
Saini, Sarbjit S.
中科院分区：
文献类型：
--
作者：
MacGlashan, Donald W., Jr.;Savage, Jessica H.;Saini, Sarbjit S.
背景：最近一项用omalizumab治疗花生过敏受试者的研究产生了一些结果，这些结果与用omalizumab治疗猫过敏受试者的研究一致。然而，存在的差异提供了额外的洞察过敏受试者的细胞反应的性质。目的：我们试图确定omalizumab治疗期间未能抑制过敏原诱导的嗜碱性粒细胞反应的原因。方法：采用奥玛单抗治疗花生过敏患者。3次获得与受试者反应相关的临床、血清学和细胞指标及其外周血嗜碱性粒细胞值（特异性/总IgE比、细胞表面FceRI表达、抗IgE抗体或花生过敏原组胺释放反应）。结果：治疗后，大约60%的受试者对花生过敏原的嗜碱性粒细胞反应没有显著降低。在40%的病例中，体外嗜碱性细胞对花生过敏原的反应增加了2- 7倍。这种增加与两个主要因素有关：高特异性/总IgE比率（约10%）和嗜碱性粒细胞对IgE介导的刺激的内在反应增加。嗜碱性粒细胞对花生过敏原的反应增加的程度与患者耐受花生摄入能力的改善呈负相关。结论：omalizumab治疗期间的嗜碱性粒细胞反应是两个竞争因素的结果：细胞表面的过敏原特异性IgE抑制和对IgE介导刺激的内在敏感性增加。在花生过敏受试者中，嗜碱性粒细胞反应似乎减轻了omalizumab改善患者口服过敏原耐受性的能力。[J] .中华过敏症杂志，2012;30(3):391 - 391。
Background: A recent study of subjects with peanut allergy treated with omalizumab generated some results that were concordant with a study of subjects with cat allergy treated with omalizumab. However, there were differences that provided additional insight into the nature of the cellular responses in allergic subjects.Objective: We sought to determine the cause for failure to suppress the allergen-induced basophil response during treatment with omalizumab.Methods: Patients with peanut allergy were treated with omalizumab. Clinical, serologic, and cellular indices relevant to the response of the subjects and their peripheral blood basophil values (specific/total IgE ratio, cell-surface FceRI expression, and histamine release responses to anti-IgE antibody or peanut allergen) were obtained at 3 times.Results: After treatment, approximately 60% of the subjects' basophil responses to peanut allergen did not significantly decrease. In 40% of cases, the in vitro basophil response to peanut allergen increased 2- to 7-fold. The increases were associated with 2 primary factors: a high (>10%) specific/total IgE ratio and an increase in the intrinsic response of the basophil to IgE-mediated stimulation. The extent to which the basophil response to peanut allergen increased was inversely correlated with improvement in the patient's ability to tolerate ingestion of peanut.Conclusion: The basophil response during treatment with omalizumab is a consequence of 2 competing factors: suppression of allergen-specific IgE on the cell surface versus increased intrinsic sensitivity to IgE-mediated stimulation. In subjects with peanut allergy, the basophil response appears to mitigate against the ability of omalizumab to improve the patient's tolerance of oral allergen. (J Allergy Clin Immunol 2012;130:1130-5.)