Allergen‐Specific IgE and IgG4 Signatures in IgG4 ‐Related Disease Revealed by a Large‐Scale PhIP ‐Seq Study

作者：Zhan Li, Songxin Yan, Jialei Zhang, Haolong Li, Ziyan Wu, Linlin Cheng, Yongmei Liu, Haoting Zhan, Honglin Xu, Futai Feng, Jingdi Zhang, Siyu Wang, Xinxin Feng, Changcheng Yin, Linyi Peng, Jiaxin Zhou, Yunyun Fei, Wen Zhang, Yongzhe Li · 发表于：Allergy · 年份：2025 · DOI：10.1111/all.70162 · 被引用次数：4 · 研究领域：IgG4-Related and Inflammatory Diseases、Sinusitis and nasal conditions、Allergic Rhinitis and Sensitization

OBJECTIVES: Immunoglobulin G4-related disease (IgG4-RD) is frequently accompanied by allergic/atopic manifestations, yet its allergen-specific antibody landscape remains poorly defined. Therefore, we detected allergen-specific IgE and IgG4 levels in patients with IgG4-RD to clarify their contribution to IgG4-RD pathogenesis. METHODS: In total, 826 plasma samples from 370 patients with IgG4-RD and 354 healthy controls were used to perform Phage Immunoprecipitation Sequencing. Follow-up samples from 102 patients (median 3 years) captured temporal dynamics. Machine learning (XGBoost) was used to identify key allergen peptides. ELISA was used for validation in 51 IgG4-RD patients and 24 healthy controls, including an independent cohort of 20 treatment-naïve patients. RESULTS: Abnormal IgE and IgG4 allergen reactivity was observed in IgG4-RD patients. Enhanced responses to Apis mellifera and Arachis hypogaea were particularly prominent and correlated with lacrimal gland, parotid gland, paranasal, pulmonary, renal (A. mellifera) and pancreatic (A. hypogaea) involvement. XGBoost achieved an AUC of 0.91-0.96 and consistently ranked 10 peptides, mainly from bee, peanut, vespid-venom and fish allergens. ELISA confirmed significantly elevated Ara h 1-specific IgG4 in IgG4-RD. Follow-up sampling showed a global decline in reactivity to most top allergens and an IgE-to-IgG4 shift to Staphylococcus aureus peptides, suggesting therapy-associated modulation and emerging tolerance. CONCLUSION...