Improved FcεRI-Mediated CD203c Basophil Responsiveness Reflects Rapid Responses to Omalizumab in Chronic Spontaneous Urticaria

J Allergy Clin Immunol Pract. 2021 Mar;9(3):1166-1176.e8. doi: 10.1016/j.jaip.2020.08.048. Epub 2020 Sep 6.

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Increased basophil responsiveness via FcεRI after omalizumab treatment is associated with the therapeutic effect and mechanism of action of omalizumab.

Keywords: Basophil activation test; CD203c; Chronic spontaneous urticaria; Omalizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Allergic Agents* / therapeutic use
  • Basophils
  • Chronic Urticaria*
  • Humans
  • Immunoglobulin E
  • Omalizumab / therapeutic use
  • Receptors, IgE
  • Urticaria* / drug therapy

Substances

  • Anti-Allergic Agents
  • Receptors, IgE
  • Omalizumab
  • Immunoglobulin E