Abstract
PURPOSE: Chronic spontaneous urticaria (CSU) is a mast cell-driven skin disorder characterized by a complex pathogenesis involving immune dysregulation and inflammation. MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators in various diseases. This study aimed to investigate differentially expressed serum miRNAs in CSU and its association with treatment response. METHODS: Thirty CSU patients (37.9 ± 9.8 years, 15 females) and 10 normal controls were enrolled. Patients were stratified by clinical response to H₁-antihistamines (H1AHs) and omalizumab. Serum miRNAs were profiled using the Affymetrix GeneChip(®) miRNA 4.0 Array. Differentially expressed miRNAs were identified, and bioinformatic analyses were performed to predict target genes and assess pathway enrichment. RESULTS: Eighteen miRNAs were differentially expressed between CSU patients and normal controls, with 10 upregulated and 8 downregulated in CSU. Compared to H1AH responders, 23 miRNAs were downregulated in H1AH nonresponders. In omalizumab-treated patients, 4 miRNAs, hsa-miR-503-5p, hsa-miR-1282, hsa-miR-93-5p, and hsa-miR-638, were reduced in complete responders. Bioinformatic analysis identified 3 hub genes (MYC proto-oncogene [MYC], cyclin D1 [CCND1], ribonucleotide reductase regulatory subunit M2) in H1AH nonresponse, and 14 key target genes, including heat shock protein family A (Hsp70) member 8 (HSPA8), CCND1, and E2F transcription factor 3, in omalizumab complete responders. Notably, hsa-miR-93-5p and its predicted target CCND1 were associated with both H1AH nonresponsiveness and omalizumab complete response. CONCLUSIONS: Distinct serum miRNA signatures are associated with treatment responses in CSU. In particular, miR-93-5p with network targets, including MYC, CCND1, and HSPA8, indicates shared regulatory pathways underlying H1AH refractoriness and omalizumab responsiveness. These findings offer mechanistic insights into CSU pathogenesis and support a personalized approach to treatment.