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

Publication date: Available online 5 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Oliver Schmetzer, Elisa Lakin, Fatih A. Topal, Patricia Preusse, Denise Freier, Martin K. Church, Marcus Maurer
BackgroundThe efficacy of omalizumab (anti-IgE) and elevated IgE levels in chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms.ObjectiveTo identify autoallergic targets of IgE in CSU patients.MethodsSera of CSU patients together with idiopathic anaphylaxis patients and healthy controls (seven of each) were screened for IgE-autoantibodies using an array of >9,000 proteins. Sera of 1062 CSU patients and 482 healthy controls were used in an IgE-anti-Interleukin-24 (IL-24) specific ELISA to investigate the association of IgE-anti-IL-24 and CSU.ResultsBy array analyses, over 200 IgE-autoantigens were found in CSU patients that were not in controls. Of the 31 IgE-autoantigens detected in >70% of patients, eight were soluble or membrane bound and expressed in skin. Of these, only IgE-autoantibodies to IL-24 were found in all CSU patients. In vitro studies showed IL-24 to release histamine from human mast cells sensitized with purified IgE of CSU patients but not controls. By ELISA analyses, the mean ± SD levels of IgE-anti-IL-24 were 0.52 ± 0.24 IU/ml in CSU and 0.27 ± 0.08 IU/ml in controls with 80% of CSU patients but only 20% of controls having levels >0.33 IU/ml (P< 0.0001). IgE-anti-IL-24 showed acceptable predictive properties for CSU, with a likelihood ratio of 3.9. Clinically, IgE-anti-IL-24 levels showed an association with disease activity as assessed by the urticaria activity score and with reduced basophil counts.ConclusionOur findings show that CSU patients frequently exhibit IgE-autoantibodies against many autoantigens and that IL-24 is a common, specific, and functional autoantigen of IgE-antibodies in CSU.



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