Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
J Allergy Clin Immunol Pract. 2021 Mar;9(3):1166-1176.e8. doi: 10.1016/j.jaip.2020.08.048. Epub 2020 Sep 6.
Omalizumab is effective in patients with chronic spontaneous urticaria (CSU) although its mechanism of action is poorly understood. Several studies reported that decreased high-affinity IgE receptor (FcεRI)-mediated histamine release and/or responsiveness was characteristic of basophils in patients with CSU. However, few studies have focused on the relationship between changes in basophil responsiveness via FcεRI after omalizumab treatment and the therapeutic effect in patients with CSU.
To assess basophil responsiveness via FcεRI stimulation, as well as FcεRI expression and IgE binding on blood basophils from patients with CSU before and after omalizumab treatment and its possible association with the clinical response.
We analyzed 34 patients with CSU treated with omalizumab who were categorized as fast responders (FRs) (n = 20) and non or slow responders (N/SRs) (n = 14). CD203c expression induced by FcεRI stimulation, and IgE and FcεRI expressions on blood basophils from patients with CSU before and after omalizumab treatment were analyzed. Basophil responsiveness via FcεRI stimulation was observed in vitro using basophils pretreated with omalizumab.
FRs had increased CD203c responsiveness after treatment with omalizumab compared with N/SRs. This improvement of basophil responsiveness via FcεRI stimulation in FRs was not observed in peripheral blood basophils preincubated with omalizumab in vitro, suggesting that omalizumab does not directly affect circulating pre-existing abnormal basophils.
Increased basophil responsiveness via FcεRI after omalizumab treatment is associated with the therapeutic effect and mechanism of action of omalizumab.
奥马珠单抗对慢性自发性荨麻疹（CSU）患者有效，但其作用机制尚不清楚。几项研究报告称，CSU 患者的嗜碱性粒细胞存在高亲和力 IgE 受体（FcεRI）介导的组胺释放和/或反应性降低的特征。然而，很少有研究关注奥马珠单抗治疗后 FcεRI 介导的嗜碱性粒细胞反应性变化与 CSU 患者治疗效果之间的关系。
评估奥马珠单抗治疗前后 CSU 患者嗜碱性粒细胞通过 FcεRI 刺激的反应性以及 FcεRI 表达和 IgE 结合，并探讨其与临床反应的可能相关性。
我们分析了 34 例接受奥马珠单抗治疗的 CSU 患者，将其分为快速应答者（FRs）（n=20）和非或缓慢应答者（N/SRs）（n=14）。分析了奥马珠单抗治疗前后 CSU 患者嗜碱性粒细胞的 FcεRI 刺激诱导的 CD203c 表达以及 IgE 和 FcεRI 表达。通过用奥马珠单抗预处理嗜碱性粒细胞，在体外观察 FcεRI 刺激对嗜碱性粒细胞的反应性。
与 N/SRs 相比，FRs 在接受奥马珠单抗治疗后 CD203c 反应性增加。在体外预先用奥马珠单抗孵育外周血嗜碱性粒细胞时，FRs 通过 FcεRI 刺激的嗜碱性粒细胞反应性的这种改善并未观察到，这表明奥马珠单抗不会直接影响循环中预先存在的异常嗜碱性粒细胞。
奥马珠单抗治疗后 FcεRI 介导的嗜碱性粒细胞反应性增加与奥马珠单抗的治疗效果和作用机制相关。
