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

Autor: Ji Y; Department of General Practice Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical school, Shenzhen 518060, China., Wang E; Department of General Practice Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China., Mohammed MT; Faculty of Veterinary medicine, University of Kufa, Kufa, Iraq; School of Infection and Immunity, 120 University Place, University of Glasgow, Glasgow, UK., Hameed N; School of Infection and Immunity, 120 University Place, University of Glasgow, Glasgow, UK., Christodoulou MI; School of Infection and Immunity, 120 University Place, University of Glasgow, Glasgow, UK; Tumor Immunology and Biomarkers Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 2404, Cyprus., Liu X; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen, China., Zhou W; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen, China., Fang Z; Department of General Practice Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen, China., Jia N; Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangdong, China., Yu H; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen, China; Department of Respiratory and Critical Care Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China., Zhou Z; Clinical Laboratory, Longgang District Maternity and Child Healthcare Hospital, Shenzhen, Guangdong, China., Sun Y; Department of Immunology, School of Basic Medical Science, Capital Medical University, Beijing, China., Huang SK; Department of General Practice Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China; National Institute of Environmental Health Sciences, National Health Research Institutes, Taipei, Taiwan, China; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States., McSharry C; School of Infection and Immunity, 120 University Place, University of Glasgow, Glasgow, UK., Zhong NS; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangdong, China., Xiao X; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen, China. Electronic address: xiaojun1985918@szu.edu.cn., Li J; Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangdong, China. Electronic address: lijing@gird.cn., Xu D; Department of General Practice Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen, China. Electronic address: xdm@szu.edu.cn.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2024 Jul; Vol. 264, pp. 110234. Date of Electronic Publication: 2024 May 11.
DOI: 10.1016/j.clim.2024.110234
Abstrakt: Background: 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.
Methods: 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.
Results: 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 FEF 25 - 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.
Conclusions: 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.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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