TY - JOUR T1 - Dermal nerve growth factor is increased in prurigo nodularis compared to atopic dermatitis JF - bioRxiv DO - 10.1101/2022.06.15.496275 SP - 2022.06.15.496275 AU - Junwen Deng AU - Varsha Parthasarathy AU - Zachary Bordeaux AU - Melika Marani AU - Kevin Lee AU - Chi Trinh AU - Nishadh Sutaria AU - Hannah L. Cornman AU - Anusha Kambala AU - Thomas Pritchard AU - Shihua Chen AU - Olusola O. Oladipo AU - Madan M. Kwatra AU - Martin P. Alphonse AU - Shawn G. Kwatra Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/06/17/2022.06.15.496275.abstract N2 - Background Prurigo nodularis (PN) is a chronic, pruritic, inflammatory skin disease characterized by hyperkeratotic nodules on the trunk and extremities. While there is growing research on the immunological basis of PN, the neuropathic and structural components of PN lesions are unknown.Objective To determine the inflammatory, neuropathic, and structural pathways in PN compared to atopic dermatitis (AD).Methods Lesional and non-lesional skin biopsies were collected from 13 PN and 6 AD patients. mRNA and protein expression in biopsies was determined using RNA-Sequencing and immunohistochemistry (IHC), respectively. Differentially expressed genes (DEGs) were identified using the DESeq2 R package and pathway level enrichment was determined using Gene Set Enrichment Analysis. IHC expression was quantified with QuPath followed by statistical comparison with the Student’s t-test and Mann-Whitney U.Results Compared to lesional AD, lesional PN had greater mRNA expression of MMPs, OSM, NGF, IL1β, CXCL2, CXCL5, CXCL8, and insulin-like growth factors, and lower expression of CCL13, CCL26, EPHB1, and collagens. Compared to non-lesional AD, non-lesional PN showed upregulation of keratin-family genes. GSEA revealed that lesional PN had greater keratinization, cornified envelope, myelin sheath, TGF-beta signaling, extracellular matrix disassembly, metalloendopeptidase activity, and neutrotrophin-TRK receptor signaling, while non-lesional PN had higher keratin filament, extracellular structure organization, extracellular matrix disassembly, and angiogenesis. IHC showed increased dermal nerve growth factor (NGF) expression in lesional PN compared to lesional AD (p=0.038), and greater epidermal NGF compared to dermal NGF in non-lesional PN (p=0.014).Limitations Single, tertiary care center.Conclusions PN demonstrated increased neurotrophic and extracellular matrix (ECM) remodeling signatures compared to AD, possibly explaining the morphological differences in their lesions. These signatures may therefore be important components of the PN pathogenesis and may serve as therapeutic targets.Competing Interest StatementShawn G. Kwatra is an advisory board member/consultant for Abbvie, Celldex Therapeutics, Galderma, Incyte Corporation, Pfizer, Regeneron Pharmaceuticals, and Kiniksa Pharmaceuticals and has served as an investigator for Galderma, Kiniksa Pharmaceuticals, Pfizer Inc., and Sanofi. ER -