IgM and IgA in addition to IgG autoantibodies against FcɛRIα are frequent and associated with disease markers of chronic spontaneous urticaria

Altrichter, Sabine; Zampeli, Vasiliki; Ellrich, André; Zhang, Ke; Church, Martin K.; Maurer, Marcus

doi:10.1111/all.14412

Cited by 60 publications

(45 citation statements)

References 48 publications

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“…Antigen-IgE interactions are not involved in the degranulation of mast cells that drive the development of wheals and angioedema in TIIbaiCSU. In TIIbaiCSU, mast cell degranulation is due to IgG or IgM autoantibodies to the high-affinity IgE receptor FcεRIα, 49 50 or IgE bound to it. 51 The ability of these autoantibodies to degranulate mast cells is linked to the expression levels of its targets, FcεRIα and IgE, on the surface of mast cells.…”

Section: The Role Of Ige In Tiibaicsumentioning

confidence: 99%

Total IgE as a Marker for Chronic Spontaneous Urticaria

Altrichter

Fok

Jiao

et al. 2021

Allergy Asthma Immunol Res

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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.

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Section: The Role Of Ige In Tiibaicsumentioning

confidence: 99%

Total IgE as a Marker for Chronic Spontaneous Urticaria

Altrichter

Fok

Jiao

et al. 2021

Allergy Asthma Immunol Res

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“…The exact mechanisms leading to the activation of mast cells, the key pathogenic drivers of the development of the signs and symptoms (itch, wheals, and angioedema) in patients with CSU, are not fully characterized. There is, however, strong indication that autoimmunity, either “autoallergic” (type I, with IgE antibodies to self‐antigens/allergens) or “autoimmune” (type IIb, with IgG and IgM autoantibodies to IgE or its high‐affinity receptor (FcεRI)) is the most frequent cause of CSU 6‐9 . Many co‐factors can be involved in modulating the activation status of mast cells, such as physical agents, pseudoallergens, neuropeptides, or bacterial products and the local inflammatory milieu, with activated eosinophils, basophils, and neutrophils infiltrating the skin 10,11 …”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines

Agache

Rocha

Pereira

et al. 2020

Allergy

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This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) −5; 95%CI −7.75 to −2.25), and the itch severity score (ISS)7 (MD −2.15; 95% CI −3.2 to −1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD −2.01; 95%CI −3.22 to −0.81) and decreases (moderate certainty) rescue medication use (MD −1.68; 95%CI −2.95 to −0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD −11.05; 95%CI −12.87 to −9.24), the ISS7 (MD −4.45; 95%CI −5.39 to −3.51), and QoL (high certainty) (DLQI; MD −4.03; 95% CI −5.56 to −2.5) and decreases (moderate certainty) rescue medication use (MD −2.04; 95%CI −3.19 to −0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91).

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“…In chronic spontaneous urticaria (CSU), the activation of skin MCs via FcεRI, either by IgE to autoallergens or by autoantibodies to its alpha chain, is held to drive the development of signs and symptoms, itchy wheals and angioedema, in most patients 100,101 . Treatment with omalizumab, an anti-IgE antibody, is effective in CSU 102 and prevents MC activation by reducing the levels of free IgE and FcεRI expression.…”

Section: Treatments That Inhibit Mast Cell Activationmentioning

confidence: 99%

The Ingenious Mast Cell: Contemporary insights into mast cell behavior and function

Dahlin¹,

Maurer²,

Metclafe³

et al. 2020

Preprint

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Mast cells are (in)famous for their role in allergic diseases, but the physiological and pathophysiological roles of this ingenious cell are still not fully understood. Mast cells are important for homeostasis and surveillance of the human system, recognizing both endogenous and exogenous agents, which induce release of a variety of mediators acting on both immune and non-immune cells, including nerve cells, fibroblasts, endothelial cells, smooth muscle cells and epithelial cells. During recent years, clinical and experimental studies on human mast cells as well as experiments using animal models have resulted in many discoveries that help decipher the function of mast cells in health and disease. In this review we focus particularly on new insights into mast cell biology, with a focus on mast cell development, recruitment, heterogeneity and reactivity. We also highlight the development in our understanding of mast cell driven-diseases and discuss the development of novel strategies to treat such conditions.

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IgM and IgA in addition to IgG autoantibodies against FcɛRIα are frequent and associated with disease markers of chronic spontaneous urticaria

Cited by 60 publications

References 48 publications

Total IgE as a Marker for Chronic Spontaneous Urticaria

Total IgE as a Marker for Chronic Spontaneous Urticaria

Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines

The Ingenious Mast Cell: Contemporary insights into mast cell behavior and function

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