Characterization of the clinical relevance and hypoallergenic peptides of the newly evidenced major allergen Hum j 1

• Published in: Frontiers in immunology Vol. 16; p. 1588870
• Main Authors: Cheng, Ya-Li, Li, Qiong, Yang, Yong-Shi, Hou, Yi-Bo, Xu, Zhi-Qiang, Wei, Ji-Fu, Sun, Jin-Lyu
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 23.06.2025
• Subjects: Adolescent; Adult; Allergens - immunology; allergic asthma; allergy diagnosis; Animals; Antigens, Plant - immunology; Basophils - immunology; Clinical Relevance; Female; Hum j 1; Humans; Humulus japonicus pollen; hypoallergenic peptides; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G - immunology; Immunology; Male; Mice; Middle Aged; Peptides - immunology; Plant Proteins - immunology; Pollen - immunology; Rhinitis, Allergic, Seasonal - diagnosis; Rhinitis, Allergic, Seasonal - immunology; Young Adult; allergy diagnosis; Humulus japonicus pollen; allergic asthma; Hum j 1; hypoallergenic peptides
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2025.1588870

(HJ) pollen is a predominant autumn allergen in northern China. Two decades ago, a 10 kDa protein termed Hum j 1 was proposed as a major allergen, but its uncertainty hindered its clinical application. This study aims to investigate the clinical relevance of Hum j 1 and screen hypoallergenic peptides for potential application in molecular diagnosis and immunotherapy. Serum samples from 93 HJ pollen-allergic patients were analyzed for IgE reactivity against recombinant Hum j 1 (rHum j 1). We evaluated correlations between IgE responses to rHum j 1 and HJ pollen crude extracts using Spearman's rank correlation analysis. The association between clinical symptoms and Hum j 1-IgE positivity was evaluated by group comparisons and multivariable analyses. Allergenicity of Hum j 1 was further investigated by immunoblotting and basophil activation tests. Six KLH-coupled peptides (21-25 amino acids) spanning the complete Hum j 1 sequence were synthesized to assess hypoallergenicity and IgG-mediated inhibitory effects against allergen-specific IgE binding using a murine passive immunization model. rHum j 1 demonstrated IgE reactivity in 74.2% (69/93) of the patients and induced significant basophil activation. rHum j 1-specific IgE levels showed a moderate positive correlation with crude extract-specific IgE levels (Spearman's ρ = 0.529, < 0.0001). Patients with allergic rhinitis complicated by asthma had significantly higher levels of Hum j 1-sIgE ( = 0.014). We found a significant association between Hum j 1 sensitization and asthma in the multivariate analysis [odds ratio (OR) = 3.98, 95% confidence interval (CI): 1.2-13.0, = 0.02], with Hum j 1-sensitized patients showing higher asthma prevalence compared to non-sensitized individuals (46% vs. 17%, = 0.010). All six peptides showed significantly reduced IgE reactivity ( < 0.0001) and minimal basophil activation. Immunized mice produced high-titer IgG antibodies that inhibited patient IgE binding to rHum j 1 by 22.09%-64.61%. Hum j 1 could enhance the sensitivity of HJ pollen crude extract-based IgE assays. IgE reactivity to Hum j 1 was more frequently associated with allergic asthma. The hypoallergenic linear peptides of Hum j 1 laid the foundation for the development of a molecular vaccine for allergen-specific immunotherapy. These findings would contribute to developing diagnostic and therapeutic strategies for HJ pollinosis.