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

Autor: Tay SH; Division of Rheumatology, Department of Medicine, National University Hospital, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: sen_hee_tay@nuhs.edu.sg., Santosa A; Division of Rheumatology, Department of Medicine, National University Hospital, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Goh ECH; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Xu CX; Department of Nursing, National University Hospital, Singapore, Singapore., Wu LH; Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore., Bigliardi-Qi M; Department of Dermatology and Stem Cell Institute, University of Minnesota, Minneapolis, Minn., Pakkiri LSS; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Lee BTK; Centre for Biomedical Informatics, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Drum CL; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Cardiology, National University Heart Center, National University Hospital, Singapore, Singapore., Bigliardi PL; Department of Dermatology, University of Minnesota, Minneapolis, Minn.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2022 Dec; Vol. 150 (6), pp. 1486-1497. Date of Electronic Publication: 2022 Aug 12.
DOI: 10.1016/j.jaci.2022.07.025
Abstrakt: 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 significantly correlated expression patterns in the IL-22 pathway. To validate the transcriptomics data, IL-22 was measured in the plasma samples of the subjects using ELISA. IL-22 was significantly higher in preaspirin desensitization patients compared with controls. In parallel, metabolomic analysis revealed stark differences in plasma profiles of preaspirin desensitization patients and healthy controls. In particular, 2-hydroxybenzoic acid (salicylic acid) was significantly lower in preaspirin desensitization patients compared with healthy controls.
Conclusions: This is the first study to combine both transcriptomic and metabolomic approaches in patients with NIUA, which contributes to a deeper understanding about the pathogenesis of NIUA and may potentially pave the way toward a molecular diagnosis of NSAID hypersensitivity.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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