Study Links MRGPRX3 Expression to Chronic Pruritus in PN and AD

Key Takeaways

• MRGPRX3 expression is significantly increased in lesional skin of both prurigo nodularis and atopic dermatitis (AD) compared with non-lesional and healthy skin, according to a poster at AAD 2026. 
• Somatic mutations in MRGPRX3-related genes were associated with race (β = 16; 95% CI, 7-25; P < 0.001).
• Findings support a potential role for MRGPRX3 in chronic pruritus pathogenesis and as a therapeutic target

In a prospective analysis of skin biopsies, investigators reported significantly elevated cutaneous MRGPRX3 expression in lesional prurigo nodularis (PN) and atopic dermatitis (AD), alongside a notable association between MRGPRX3-related gene mutations and Black participants.

Study authors evaluated adults with PN (n = 10), AD (n = 5), and healthy controls (n = 10), using immunofluorescence (IF) staining to quantify MRGPRX3 expression and genomic analyses to assess related gene mutations. Fluorescence intensity was compared across groups using analysis of variance, with additional multivariable linear regression to explore associations with demographic and clinical variables.

The data indicated lesional PN and AD skin showed significantly higher MRGPRX3 expression vs both non-lesional skin and healthy controls (P < 0.05 for all comparisons). Non-lesional skin showed lower expression levels.

Genomic analysis identified a significant association between Black race and somatic mutations in MRGPRX3-related genes (β = 16; 95% CI, 7-25; P < 0.001). No significant associations were observed with age, sex, disease type, lesion status, or Worst-Itch Numeric Rating Scale scores.

Small sample size and cross-sectional design were cited as significant limitations.

“These novel findings demonstrate upregulation of cutaneous MRGPRX3 in PN and AD and suggest racial differences in somatic alterations in MrgprX3-related genes,” the authors wrote in their poster. “These data supports a potential role for MRGPRX3 in the pathogenesis of chronic pruritus, particularly in Black patients.”

Source: Marani M, et al. Prurigo nodularis and atopic dermatitis feature increased cutaneous expression of MRGPRX3. Poster 71340. Presented at: American Academy of Dermatology Annual Meeting; March 27-31, 2026; Denver.