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Patients with NSAID hypersensitivity have distinct transcriptomics and metabolomics profiles

Published: August 11, 2022

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most highly consumed medications worldwide because of their efficacy in the treatment of pain and other inflammatory conditions. Despite their prevalent use, aspirin and NSAIDs are among the most common causes of adverse drug reactions, accounting for 21-25% of all reactions. Most of these cases are cross-reactive hypersensitivity reactions in form of a cyclooxygenase-1 intolerance, in which patients react to aspirin and NSAIDs from different chemical groups based on the mode of action and in the absence of specific immunological recognition. NSAID-induced urticaria/angioedema (NIUA) is the most frequent form of NSAID hypersensitivity in adults, representing more than 60% of all reactions. Oral drug provocation tests (DPTs) remain the gold standard for the diagnosis of NIUA. However, DPTs are time-consuming, represent a risk for patients and need to be interpreted carefully. Hence, there is an urgent need to develop in vitro tests to reliably diagnose and monitor patients with NIUA.

In this paper published in The Journal of Allergy and Clinical Immunology (JACI), Tay et al. characterized the transcriptomic and metabolomic profiles of patients with NIUA undergoing aspirin desensitization. Transcriptomics is the genome-wide measurement of transcripts while metabolomics is the systematic identification and quantification of all metabolites. Peripheral blood mononuclear cells and plasma were separated from the blood of NIUA patients undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls.  RNA was isolated from PBMCs and subjected to mRNA- and lncRNA-seq. Plasma samples were analyzed using LC-MS/MS for metabolite shifts using a semi-targeted metabolomics panel.  The principal findings of this study include: (i) distinct transcriptomic and metabolomic profiles characterize NIUA patients undergoing aspirin desensitization; (ii) low-dose aspirin desensitization significantly downregulates the “NSAID hypersensitivity signature” in NIUA patients and (iii) NIUA patients have low levels of baseline salicylic acid compared to NSAID-tolerant controls.

This is the first study to simultaneously quantify transcripts and metabolites in NIUA patients. This paper contributes to the field by describing the unique transcriptomic and metabolomic profiles of patients with NIUA, which may potentially pave the way towards a molecular diagnosis of NSAID hypersensitivity.

The Journal of Allergy and Clinical Immunology is an official scientific journal of the AAAAI and is the most-cited journal in the field of allergy and clinical immunology.

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