Prurigo NodularisにおけるADGRE2をバイオマーカーとして強調する骨髄細胞由来の炎症：統合マルチオミクス解析

Prurigo nodularis (PN) is a chronic pruritic skin disease characterized by hyperkeratotic nodules and intense itching, yet its pathological mechanisms remain unclear, especially at the protein level and in comparison to atopic dermatitis (AD). We performed parallel analyses of proteomic data (4D-DIA) from lesions of PN, AD, and healthy controls (HC). Single-cell RNA sequencing data were integrated from publicly available datasets (e.g., GSE222840) representing comparable cohorts. Our analysis revealed a PN-specific proteomic signature dominated by myeloid-driven immunity, profound tissue remodeling, and mitochondrial metabolic reprogramming. From this signature, we identified a set of PN-enriched molecules. Among them, Adhesion G Protein-Coupled Receptor E2 (ADGRE2)-a known mechanosensory receptor-emerged as the most selectively upregulated in PN myeloid subsets. Critically, the expression of ADGRE2 demonstrated a strong positive correlation with clinical itch severity, as measured by the peak pruritus numerical rating scale (PP_NRS) and the dermatology life quality index (DLQI). It was also further confirmed to be predominantly expressed in myeloid cells of PN lesions, showing higher abundance than in AD or HC. This study refines the PN framework, highlighting myeloid-enriched molecules such as ADGRE2, which provides mechanistic insights into the unique inflammatory and sensory landscape and offers therapeutic avenues.