IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria - 06/09/18
, Elisa Lakin, Fatih A. Topal, Patricia Preusse, Denise Freier, Martin K. Church, PhD, DSc, Marcus Maurer, MDAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : IL-24, IgE, autoantibody, autoallergen, autoallergy, type I hypersensitivity, chronic spontaneous urticaria, wheal and flare, protein microarray, urticaria activity score
Abbreviations used : CSU, IdA, IgE-AA, IgE-AAb, PSCMC, TPBS, TPO, UAS7
Plan
| Disclosure of potential conflict of interest: M. K. Church has consultant arrangements with FAES Pharma; has received grants from Almirall, FAES Pharma, Menarini, MSD, Novartis, UCB Pharma, Sanofi-Aventis, and Uriach; and has received payment for manuscript preparation from FAES Pharma. M. Maurer has board memberships with Novartis, Genentech, Uriach, Menarini, FAES, and Moxie; has consultant arrangements with Novartis, Genentech, Uriach, Menarini, FAES, and Moxie; has provided expert testimony for Novartis, Genentech, Uriach, Menarini, FAES, and Moxie; has received grants from Novartis, Genentech, Uriach, Menarini, FAES, and Moxie; and has received payment for lectures from Novartis, Genentech, Uriach, Menarini, FAES, and Moxie. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 3
P. 876-882 - septembre 2018 Retour au numéro
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