2.6
2023

Severe chronic spontaneous urticaria responding and not responding to omalizumab: analysis of the prognostic value of known and novel in-vitro variables

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Authors Information

1Allergology Clinic, Clinica San Carlo, Paderno Dugnano, Milan, Italy
2Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
3Unit of Dermatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
4Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
5Occupational Health Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
6Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Milan, Italy
7Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

History

Published: 15 November 2024
Accepted: 25 October 2024
Received: 26 August 2024

SUMMARY

Background. Chronic spontaneous urticaria (CSU) response to anti-IgE treatment can be rapid, late or absent. Recently, potential mechanisms of activation of mast cells alternative to FceRI, including mas-related G protein-coupled receptor X2 (MRGPRX2), activation of coagulation cascade, and activation of eosinophils have been described. We measured several potential in-vitro markers, including well-known MRGPRX2 activators, in sera of patients CSU both responding and not responding to omalizumab.
Methods. D-dimer, substance P (SP), eosinophil cationic protein (ECP), soluble MRGPRX2, IgE anti-FceRI, IgE anti-FceRII, IgG anti-FceRI and IgG anti-FceRII were measured in 32 patients with severe CSU at baseline and one week after the start of omalizumab therapy, and in 20 healthy controls.
Results. At baseline CSU patients showed significantly higher levels of D-dimer, IgE anti-FceRI, IgG anti-FceRI, and ECP (p < 0.001 in all cases), and significantly lower levels of soluble MRGPRX2 (p = 0.009) than controls. The two groups showed similar levels of IgG and IgE to FceRII and SP. One week after the first omalizumab administration there was a significant drop of IgE anti-FceRI (p < 0.001) and D-dimer (p = 0.028), in early responders. SP increased in all CSU patients (p < 0.001) irrespective of the final response to omalizumab. IgE anti-FceRI response at one week was associated with the final response to omalizumab (OR:0.12 [95%CI 0.01-1.06]).
Conclusions. Severe CSU is associated with high plasma levels of several biomarkers including D-dimer, IgE anti-FceRI, IgG anti-FceRI and ECP and low levels of soluble MRGPRX2. IgE anti-FceRI response at one week may predict the final response to omalizumab.

KEY WORDS
Chronic urticaria; Omalizumab; Biomarkers.

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European Annals of Allergy and Clinical Immunology ISSN 1764-1489 | © 2024