Asthma and Allergy Center, Johns Hopkins University, Baltimore, Md.
Asthma and Allergy Center, Johns Hopkins University, Baltimore, Md.
J Allergy Clin Immunol. 2021 Jun;147(6):2295-2304.e12. doi: 10.1016/j.jaci.2021.02.039. Epub 2021 Mar 12.
Treatment of patients with asthma or food allergy with omalizumab results in several consistent changes in circulating basophils. The multiple basophil phenotypes observed in patients with chronic spontaneous urticaria (CSU) present some unique attributes that may not respond in a similar fashion to patients with asthma or food allergy. As part of a clinical study on the therapeutic outcomes of omalizumab treatment in CSU, the basophil compartment was examined for changes in characteristics predicted by prior studies.
This study sought to examine the changes in basophil function and its relationship to auto-antibodies in serum during treatment with omalizumab.
At multiple time points before and during omalizumab treatment of patients with CSU, basophil surface IgE and FcεRI expression, cellular spleen tyrosine kinase (SYK) expression, IgE-mediated histamine release (HR), and the presence of auto-antibodies in serum were determined.
Three basophil phenotypes were enumerated in the clinical study and used to group results in this basophil study: subjects with (1) basopenia, (2) normal basophil numbers with normal IgE-mediated HR, and (3) normal basophil numbers with poor HR. Basopenia was highly associated with the presence of auto-antibodies to unoccupied FcεRI and basophil numbers did not change during treatment. Likewise, subjects who are basopenic showed no changes in SYK expression or HR during treatment. In basophils of subjects who are nonbasopenic, increases in SYK expression and HR showed the expected inverse relationship to starting SYK and HR levels. Treatment with omalizumab resulted in similar kinetics for decreases in surface FcεRI and IgE in all 3 groups.
A unifying interpretation of the results revolves around the presence of auto-antibodies to FcεRI in CSU. If present, basopenia and an absence of changes in basophils during omalizumab treatment are observed. If auto-antibodies are absent, the changes in the basophil compartment are consistent with prior studies of asthma and food allergy. These group differences also are related to efficacy of the treatment for clinical outcomes, as found in the parent clinical study.
奥马珠单抗治疗哮喘或食物过敏患者会导致循环中嗜碱性粒细胞发生多种一致的变化。慢性自发性荨麻疹（CSU）患者中观察到的多种嗜碱性粒细胞表型具有一些独特的特征，这些特征可能不会以类似于哮喘或食物过敏患者的方式产生类似的反应。作为奥马珠单抗治疗 CSU 临床研究的一部分，对嗜碱性粒细胞群进行了检查，以研究其特征变化，这些变化是先前研究预测的。
本研究旨在研究奥马珠单抗治疗 CSU 期间嗜碱性粒细胞功能及其与血清中自身抗体的关系变化。
在 CSU 患者接受奥马珠单抗治疗之前和治疗期间的多个时间点，测定嗜碱性粒细胞表面 IgE 和 FcεRI 表达、细胞脾酪氨酸激酶（SYK）表达、IgE 介导的组胺释放（HR）以及血清中自身抗体的存在情况。
在这项嗜碱性粒细胞研究中，使用临床研究中计数的三种嗜碱性粒细胞表型对结果进行分组：（1）嗜碱性粒细胞减少，（2）正常嗜碱性粒细胞数量和正常 IgE 介导的 HR，和（3）正常嗜碱性粒细胞数量和不良 HR。嗜碱性粒细胞减少与未占据的 FcεRI 的自身抗体的存在高度相关，并且在治疗过程中嗜碱性粒细胞数量没有变化。同样，在治疗过程中，嗜碱性粒细胞减少的患者 SYK 表达或 HR 没有变化。在非嗜碱性粒细胞减少的患者中，SYK 表达和 HR 的增加与起始 SYK 和 HR 水平呈相反的关系。奥马珠单抗治疗导致所有 3 组表面 FcεRI 和 IgE 的减少具有相似的动力学。
对结果的统一解释围绕着 CSU 中 FcεRI 自身抗体的存在。如果存在，会观察到嗜碱性粒细胞减少和奥马珠单抗治疗期间嗜碱性粒细胞无变化。如果不存在自身抗体，则嗜碱性粒细胞群的变化与哮喘和食物过敏的先前研究一致。这些组间差异也与母体临床研究中发现的治疗对临床结果的疗效有关。
