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

BACKGROUND: The efficacy of omalizumab (anti-IgE) and increased IgE levels in patients with chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms. OBJECTIVE: We sought to identify autoallergic targets of IgE in patients with CSU. METHODS: Serum samples of patients with CSU together with those of patients with idiopathic anaphylaxis and healthy control subjects (7 of each) were screened for IgE autoantibodies by using an array of more than 9000 proteins. Sera of 1062 patients with CSU and 482 healthy control subjects were used in an IgE-anti-IL-24-specific ELISA to investigate the association of IgE-anti-IL-24 and CSU. RESULTS: By using array analyses, more than 200 IgE autoantigens were found in patients with CSU that were not found in control subjects. Of the 31 IgE autoantigens detected in more than 70% of patients, 8 were soluble or membrane bound and expressed in the skin. Of these, only IgE autoantibodies to IL-24 were found in all patients with CSU. In vitro studies showed IL-24 to release histamine from human mast cells sensitized with purified IgE of patients with CSU but not control subjects. By using ELISA, mean ± SD levels of IgE-anti-IL-24 were 0.52 ± 0.24 IU/mL in patients with CSU and 0.27 ± 0.08 IU/mL in control subjects, with 80% of patients with CSU but only 20% of control subjects having levels greater than 0.33 IU/mL (P < .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. CONCLUSION: 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.

The role of IL-17, IL-23 and IL-31, IL-33 in allergic skin diseases.

PURPOSE OF REVIEW: Allergic skin diseases such as urticaria, atopic dermatitis and allergic contact dermatitis are among the most common skin diseases with severe socioeconomic consequences. The pathogenesis of allergic skin diseases is complex. This review provides an overview of cytocines IL-17, IL-23, IL-31 and IL-33. RECENT FINDINGS: Current research results show a variety of immunological processes in the pathogenesis of the allergic skin diseases, including the role of cytokines. In addition to the Th1 and Th2 immune response, the immune response via Th17 is becoming increasingly important in allergic skin diseases but also the cytokines IL-23, IL-31 and IL-33 have been discussed in the literature recently. Different cytokines promote in a kind of orchestra the different symptoms seen in the different allergic skin diseases, including pruritus, dermatitis, mast cell mediator release and inflammation. SUMMARY: We are still in the early stages of understanding pathophysiology of allergic skin diseases and the role of various cytokines in the immune system. With the development of targeted antibodies against the proinflammatory cytokines, the variety of normal therapeutic options can be expected to evolve.