The mechanisms underlying disease pathogenesis in chronic spontaneous urticaria (CSU) and improvement with omalizumab are not completely understood. To examine if the rate of clinical remission is concordant with baseline basophil features or the rate of change of IgE-dependent functions of basophils and/or plasmacytoid dendritic cells (pDC) during omalizumab therapy.

Adults (n=18) with refractory CSU were treated with omalizumab 300 mg monthly for 90 days. Subjects recorded daily Urticaria Activity Scores (UAS), and clinical assessments with blood sampling occurred at baseline and on days 1, 3, 6, 10, 20, 30, 60, and 90 following omalizumab. At baseline, subjects were categorized by basophil functional phenotypes, determined by in vitro histamine release (HR) responses to anti-IgE antibody, as CSU-responder (CSU-R) or CSU-non-responder (CSU-NR), as well as basopenic (B) or non-basopenic (NB).

At present, an understanding of disease pathways in CSU is limited to a role for skin mast cell activation via unknown triggering mechanisms. Among the proposed triggers for SMCs are IgG auto-antibodies to IgE and FcεRI in a subset of patients. A role for basophils in CSU disease has emerged given the detection of these cells at CSU skin lesions, linkage of basopenia to disease severity, and altered basophil IgE pathway phenotypes. “In this study, we confirmed the two expected basophil characteristics in CSU: basopenia and distinct anti-IgE 355 functional phenotype,” says At present, an understanding of disease pathways in CSU is limited to a role for skin mast cell activation via unknown triggering mechanisms. Among the proposed triggers for SMCs are IgG auto-antibodies to IgE and  FcεRI in a subset of patients. A role for basophils in CSU disease has emerged given the detection of these cellsat CSU skin lesions, linkage of basopenia to disease severity, and altered basophil IgE pathway phenotypes.

In this study, we confirmed the two expected basophil characteristics in CSU: basopenia and distinct anti-IgE 355 functional phenotype,” says Kirti J Johal, MD. “A primary goal of the study was to determine if these well-defined basophil phenotypes 356 would predict the clinical response to omalizumab. Dr. Johal is lead author of the study, and Allergist-Immunologist and Professor, Division of Allergy & Immunology, Department of Medicine, George Washington University School of Medicine and Health Sciences. “A primary goal of the study was to determine if these well-defined basophil phenotypes would predict the clinical response to omalizumab.”

CSU-R/NB subjects demonstrated the most rapid and complete symptom improvement. By day 6, CSU-R/NB and CSU-NR/NB had increased anti-IgE mediated basophil HR relative to baseline, and these shifts did not correlate with symptom improvement. In contrast, CSU-NR/B basophil HR did not change during therapy. The kinetics of the decrease in surface IgE/FcεRI was similar in all 3 phenotypic groups and independent of the timing of the clinical response. Likewise, pDC surface IgE/FcεRI decline and TLR-9 induced IFN-α responses did not reflect clinical change.

 

Johal KJ, et al. The Efficacy of Omalizumab Treatment in Chronic Spontaneous Urticaria is Associated with Basophil Phenotypes. J Allergy Clin Immunol. 2021 Mar 10:S0091-6749(21)00371-7. doi: 10.1016/j.jaci.2021.02.038. Epub ahead of print. PMID: 33713769.
https://pubmed.ncbi.nlm.nih.gov/33713769/