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Distinct Serum MicroRNA Signatures and mRNA Decay Pathway Dysregulation in NSAID-Exacerbated Chronic Urticaria
Young-Min Ye1, Jin Young Noh2,3,4, Seung Ho Kim3,4
1Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in chronic urticaria (CU) is linked to specific microRNA (miRNA) changes. Identifying these miRNA signatures may help in diagnosing and treating NSAID-exacerbated CU.
Area of Science:
- Immunology
- Genetics
- Dermatology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can worsen chronic urticaria (CU) in a significant patient subset.
- This NSAID-exacerbated CU (NECU) subtype involves distinct inflammatory and leukotriene-driven pathways.
- MicroRNAs (miRNAs) are key regulators of immune and inflammatory processes.
Purpose of the Study:
- To identify differentially expressed miRNAs (DEMs) in patients with NSAID-exacerbated CU (NECU) compared to NSAID-tolerant CU (NTCU).
- To elucidate the molecular networks and biological pathways associated with these DEMs in NECU.
- To explore the potential of miRNAs as biomarkers for disease endotyping and therapeutic stratification in CU.
Main Methods:
- Serum miRNA profiling was performed on 14 NECU patients and 16 NTCU patients using an Affymetrix GeneChip miRNA 4.0 Array.
- Differentially expressed miRNAs (DEMs) were identified based on fold change (>1.5) and statistical significance (p < 0.05).
- Validated miRNA targets were retrieved from the multiMiR database for network construction and Gene Ontology enrichment analysis.
Main Results:
- NECU patients showed a higher incidence of angioedema and required more systemic corticosteroid treatment.
- Eight DEMs were identified, with notable upregulation of miR-5001-5p, miR-4270, miR-6869-5p and downregulation of miR-6511b-5p, miR-2277-5p, miR-378h in NECU.
- Network analysis highlighted key clusters (e.g., AGO2-BTG2-LMNB2) involved in mRNA decay and inflammatory signaling, suggesting a role for impaired post-transcriptional regulation.
Conclusions:
- Distinct miRNA expression profiles differentiate NECU from NTCU patients.
- A potential miR-5001-5p/miR-6511b-5p-mRNA decay axis may link impaired post-transcriptional regulation to leukotriene-driven inflammation in CU.
- Identified miRNAs represent promising biomarkers for endotyping NECU and guiding targeted therapies.
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