Selective production of IL-33-neutralizing autoantibody ameliorates asthma responses and severity

Natural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunologica...

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Published in:Clinical immunology (Orlando, Fla.) Fla.), 2024-07, Vol.264, p.110234, Article 110234
Main Authors: Ji, Yuan, Wang, Eryi, Mohammed, Mohammed T., Hameed, Najwa, Christodoulou, Maria-Ioanna, Liu, Xiaoyu, Zhou, Wei, Fang, Zhangfu, Jia, Nan, Yu, Haiqiong, Zhou, Zhenwen, Sun, Ying, Huang, Shau-Ku, McSharry, Charles, Zhong, Nan-Shan, Xiao, Xiaojun, Li, Jing, Xu, Damo
Format: Article
Language:English
Subjects:
Anti-cytokine autoantibody
Asthma
IL-33
Prognosis
Severity
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Summary:Natural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunological function and clinical significance. A Luciferase Immunoprecipitation System was used to screen serum autoantibodies against 11 key cytokines in patients with allergic asthma and healthy donors. The antigen-specificity, immunomodulatory functions and clinical significance of anti-cytokine autoantibodies were determined by ELISA, qPCR, neutralization assays and statistical analysis, respectively. Potential conditions for autoantibody induction were revealed by in vitro immunization. Of 11 cytokines tested, only anti-IL-33 autoantibody was significantly increased in asthma, compare to healthy controls, and the proportion positive was higher in patients with mild-to-moderate than severe allergic asthma. In allergic asthma patients, the anti-IL-33 autoantibody level correlated negatively with serum concentration of pathogenic cytokines (e.g., IL-4, IL-13, IL-25 and IL-33), IgE, and blood eosinophil count, but positively with mid-expiratory flow FEF25–75%. The autoantibodies were predominantly IgG isotype, polyclonal and could neutralize IL-33-induced pathogenic responses in vitro and in vivo. The induction of the anti-IL-33 autoantibody in blood B-cells in vitro required peptide IL-33 antigen along with a stimulation cocktail of TLR9 agonist and cytokines IL-2, IL-4 or IL-21. Serum natural anti-IL-33 autoantibodies are selectively induced in some asthma patients. They ameliorate key asthma inflammatory responses, and may improve lung function of allergic asthma.
ISSN:1521-6616
1521-7035
1521-7035
DOI:10.1016/j.clim.2024.110234