Differential MicroRNA Expression in Chronic Spontaneous Urticaria in Relation to Treatment Response

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.

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.

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.

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.