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Review
. 2021 Mar;13(2):206-218.
doi: 10.4168/aair.2021.13.2.206.

Total IgE as a Marker for Chronic Spontaneous Urticaria

Sabine Altrichter  1 , Jie Shen Fok  1   2   3 , Qingqing Jiao  1   4 , Pavel Kolkhir  1   5 , Polina Pyatilova  1   6 , Sherezade Moñino Romero  1 , Jörg Scheffel  1 , Frank Siebenhaar  1 , Carolin Steinert  1   7 , Dorothea Terhorst-Molawi  1 , Yi Kui Xiang  1 , Martin K Church  1 , Marcus Maurer  8
Affiliations
Review

Total IgE as a Marker for Chronic Spontaneous Urticaria

Sabine Altrichter et al. Allergy Asthma Immunol Res. 2021 Mar.

Abstract

Objective: Immunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of patients with CSU has not yet been reviewed.

Methods: Publications were searched via PubMed. The search terms used were "chronic urticaria" and "total IgE." Studies were screened by titles and abstracts, and 141 were used in the review.

Results: CSU patients frequently had elevated total IgE serum levels (up to 50%), but normal or very low total IgE levels also occurred. High total IgE may represent high disease activity, longer disease duration, high chance of responding to omalizumab treatment, quick relapse after stopping omalizumab, and lower chance of responding to cyclosporine. Low IgE, in contrast, may suggest Type IIb autoimmune CSU, poor response to treatment with omalizumab and a better chance to benefits from cyclosporine treatment. Furthermore, IgE in different CSU cohorts may have different physicochemical properties that could explain differences in treatment responses to IgE-directed therapies.

Conclusion: The results of our review suggest that total IgE is a valuable marker for CSU, and we recommend its assessment in the routine diagnostic workup of CSU patients.

Keywords: Urticaria; biomarkers; chronic spontaneous urticaria; cyclosporine; diagnosis; immunoglobulin E; omalizumab; receptor; therapeutics.

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Conflict of interest statement

Sabine Altrichter is or recently was a speaker and/or advisor for and/or has received research funding from Allakos, AstraZeneca, Moxie, Sanofi and ThermoFisher.

Figures

Fig. 1
Fig. 1. Comparison of total serum IgE levels between 926 CSU patients and 36 healthy controls as measured by ImmunoCap Method (own data). Depicted are median (50%, prominent line), 25% and 75% percentile (dark shaded) as well as 10% and 90% percentile (light shaded) and extreme values (white shaded).
IgE, immunoglobulin E; CSU, chronic spontaneous urticaria.
Fig. 2
Fig. 2. IgE can exert MC activation via different mechanisms in CSU. (A) IgE bound to the high-affinity receptor subunit alpha on the surface of MC can detect (auto-)allergens and by recognition of 2 IgE molecules in close proximity downstream signal transduction is exerted, leading to MC degranulation and subsequent mediator production (type I CSU). (B) In CSU the occurrence of IgG autoantibodies directed against IgE (left) or against the high affinity receptor subunit alpha (right) can result in high affinity receptor cross-linking and MC activation (type IIb CSU). (C) Further alternative mechanisms could also lead to MC activation, e.g. unspecific IgE antibody stacking has been shown to lead to mediator production and release.
IgE, immunoglobulin E; MC, mast cell; CSU, chronic spontaneous urticaria.
See this image and copyright information in PMC

References

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