Distinct transcriptomic and metabolomic profiles characterize NSAID-induced urticaria/angioedema patients undergoing aspirin desensitization

作者：Sen Hee Tay, Amelia Santosa, Eugene Chen Howe Goh, Chunxiang Xu, Lik Hang Wu, Mei Bigliardi-Qi, Leroy Sivappiragasam Pakkiri, Bernett Teck Kwong Lee, Chester Lee Drum, Paul Bigliardi · 发表于：Journal of Allergy and Clinical Immunology · 年份：2022 · DOI：10.1016/j.jaci.2022.07.025 · 被引用次数：12 · 研究领域：Drug-Induced Adverse Reactions、Inflammatory mediators and NSAID effects、Urticaria and Related Conditions

BACKGROUND: There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA). OBJECTIVES: We sought to characterize the transcriptomic and metabolomic profiles of patients with NIUA undergoing aspirin desensitization. METHODS: PBMCs and plasma were separated from the blood of patients with NIUA undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls. RNA was isolated from PBMCs and subjected to messenger RNA (mRNA)- and long noncoding RNA (lncRNA)-sequencing. Plasma samples were analyzed using LC-MS/MS for metabolite shifts using a semitargeted metabolomics panel. RESULTS: Eleven patients with NIUA and 10 healthy controls were recruited. The mRNA gene profiles of predesensitization versus postdesensitization and healthy control versus postdesensitization did not differ significantly. However, we identified 739 mRNAs and 888 lncRNAs as differentially expressed from preaspirin desensitization patients and controls. A 12-mRNA gene signature was trained using a machine learning algorithm to distinguish between controls, postdose, and predose samples. Ingenuity Pathway Analysis identified 5 canonical pathways that were significantly enriched in preaspirin desensitization samples. IL-22 was the most upregulated pathway. To investigate the potential regulatory roles of the differentially expressed lncRNA on the mRNAs, 9 lncRNAs and 12 mRNAs showed sig...