Neuroimmune gene signature of prurigo nodularis compared to psoriasis and atopic ​​dermatitis​​

Prurigo nodularis (PN) is a debilitating neuroimmune skin disease characterized by pruritic, raised, nodular lesions. Psoriasis and AD are classically characterized by Th1/Th17 and Th2 polarization, respectively, but the neuroinflammatory profile of PN remains poorly defined. We characterized the neuroimmune phenotype of PN compared to AD, psoriasis, and healthy controls (HC), through transcriptomic analysis of lesional and nonlesional skin biopsies from 25 PN patients, 27 AD patients, 15 psoriasis patients, and 12 HC using a custom neuroinflammation-focused NanoString panel of 770 genes. Analysis of affected versus unaffected skin revealed differentially expressed genes (DEGs, fold change>1.5, p<0.05) associated with Th1, Th2, and Th17 activation in all three diseases. Upregulated DEGs in PN compared to AD and psoriasis were primarily associated with extracellular matrix remodeling or neural function. Expression of IL-31 was upregulated in PN compared to psoriasis but not AD. Downregulated DEGs in PN compared to AD were associated with Th2 activation and glutamate receptors; those compared to psoriasis were related to Th1 and Th17 activation.  PN has a distinct neuroinflammatory signature characterized by intermediate Th1/Th17 and Th2 immune axis activation compared to AD and psoriasis, with increased levels of ECM dysregulation, neuronal abnormalities, and IL-31 activity. Transcriptome analysis was performed on a total of 26 lesional and 26 non-lesional skin biopsies from 26 PN patients (mean age 52.5 years, 76% female, and 64% African American), 26 lesional and 15 nonlesional biopsies from 26 AD patients (mean age 48.5 years, 37% female, and 44% African American), and 15 lesional biopsies from 15 psoriasis patients (mean age 54.1 years, 40% female, and 47% African American) patients, as well as 12 matched controls.