The Journal of allergy and clinical immunology | 2021
The Efficacy of Omalizumab Treatment in Chronic Spontaneous Urticaria is Associated with Basophil Phenotypes.
Abstract
BACKGROUND\nThe mechanisms underlying disease pathogenesis in chronic spontaneous urticaria (CSU) and improvement with omalizumab are incompletely understood.\n\n\nOBJECTIVE\nTo 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.\n\n\nMETHODS\nAdults (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).\n\n\nRESULTS\nCSU-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.\n\n\nCONCLUSIONS\nChanges in basophil IgE based HR, surface IgE or FcεRI, bear no relationship to the kinetics in the change in clinical symptoms. Baseline basophil count and basophil functional phenotype, as determined by HR, may be predictive of responsiveness to omalizumab.