IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria

Schmetzer, Oliver; Lakin, Elisa; Topal, Fatih Alexander; Preusse, Patricia; Freier, Denise; Church, Martin K.; Maurer, Marcus

doi:10.1016/j.jaci.2017.10.035

Cited by 190 publications

(169 citation statements)

References 35 publications

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“…Of these, IgE-anti-IL-24 was found in all CSU patients indicating IL-24 to be a dermal autoantigen in CSU. 56 While this study focused on CSU, the effectiveness of omalizumab in a wide range of chronic inducible urticarias 53,57,58 suggests that similar autoantigens and IgE-dependent mechanisms may also underlie these forms of urticaria. 59 In conclusion, autoimmunity, either of Type 1 viz.…”

Section: Purported Mechanisms Of Chronic Urticariamentioning

confidence: 97%

The role and relevance of mast cells in urticaria

Church

Kolkhir

Metz

et al. 2018

Immunological Reviews

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184

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This review presents evidence that the skin mast cell, in particular the MC subtype, is the primary effector cell in urticaria. Mast cells are located in the upper dermis, the ideal situation for wheal formation and sensory nerve stimulation. Increased numbers of mast cells are found in both lesional and non-lesional skin in CSU and inducible urticaria. Mast cell degranulation in the area of wheals has been demonstrated repeatedly by light and electron microscopy. Histamine, PGD and tryptase are found in the venous blood draining wheal formation. The last 2 are specific for mast cells rather than basophils. Mast cell reactivity is increased in active urticaria by local inflammatory cytokines and neuropeptides. Mast cell cytokines and neuropeptides, particularly nerve growth factor, induce a Th2 type inflammation that is particularly obvious at the sites of whealing. In conclusion, autoimmunity, either of Type 1 viz. IgE antibodies to local autoallergens, or Type 2b, viz. IgG autoantibodies to IgE or its receptor, are considered to be the most frequent causes of CSU. In both cases, the mast cell is likely to be the axial cell in producing the wheals.

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Section: Purported Mechanisms Of Chronic Urticariamentioning

confidence: 97%

The role and relevance of mast cells in urticaria

Church

Kolkhir

Metz

et al. 2018

Immunological Reviews

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184

198

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“…A possible role of IgE‐mediated Type I autoimmunity, also referred to as autoallergy, was postulated following observations of IgE autoantibodies to thyroperoxidase . More recently, CSU patients have also been shown to have IgE against double‐stranded DNA, interleukin‐24, tissue factor, and thyroglobulin . This is supported by the high rate of CSU patients with elevated IgE levels and the fast onset of the beneficial effects of omalizumab (anti‐IgE) in many CSU patients …”

Section: Introductionmentioning

confidence: 99%

Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study

Schoepke

Asero

Ellrich

et al. 2019

Allergy

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Background: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU.Methods: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). Results:Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti-TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively.Conclusions: aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management. K E Y W O R D Sautoimmune CSU, autologous serum skin test, basophil activation assays, chronic spontaneous urticaria, IgG autoantibodies

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“…In autoallergic CSU, IgE against autoantigens is thought to be the relevant factor responsible for MC activation and thus for the elicitation of urticarial symptoms. Different groups have recently identified functional 'that is MC degranulating’ IgE against autoantigens such as thyroid peroxidase or IL‐24 and in a large proportion of CSU patients higher than normal levels of IgE are detected, with the majority of the total IgE being autoreactive . Furthermore, specific and functional IgE against staphylococcal enterotoxins has been identified in many CSU patients .…”

Section: Chronic Spontaneous Urticariamentioning

confidence: 99%

New biological treatments for asthma and skin allergies

Eyerich

Metz

Bossios

et al. 2019

Allergy

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Allergies are typically endemic, complex and heterogeneous diseases with a high impact at quality of life. Mechanistically, type 2 immune responses involving eosinophil and basophil granulocytes, mast cells and humoral factors such as IgE are key drivers of allergic diseases. Fighting allergic diseases knows three strategies: prevention, symptomatic and causative therapy. While remarkable progress was made in understanding molecular events in allergies as a prerequisite for effective prevention and desensitization, this review article focuses on the most efficient symptomatic treatments—that is using more and more specific antibodies neutralizing particular immune pathways. We highlight and classify recent and upcoming developments in the three prototype chronic allergic diseases allergic asthma, chronic spontaneous urticaria and atopic eczema. In all three examples, biologics such as dupilumab or omalizumab become reliable and efficient therapeutic options. Finally, we give an outlook how a diagnostic and therapeutic workflow might look like in the near future for these three major burdens of society.

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IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria

Abstract: Our findings show that patients with CSU frequently exhibit IgE autoantibodies against many autoantigens and that IL-24 is a common, specific, and functional autoantigen of IgE antibodies in patients with CSU.

Cited by 190 publications

References 35 publications

The role and relevance of mast cells in urticaria

The role and relevance of mast cells in urticaria

Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study

New biological treatments for asthma and skin allergies

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