Dermal nerve growth factor is increased in prurigo nodularis compared to atopic dermatitis

Deng, J.; Parthasarathy, V.; Bordeaux, Z.; Marani, M.; Lee, K.; Trinh, C.; Sutaria, N.; Cornman, H.; Kambala, A.; Pritchard, T.; Chen, S.; Oladipo, O. O.; Kwatra, M. M.; Alphonse, M. A.; Kwatra, S. G.

doi:10.1101/2022.06.15.496275

bioRxiv · 10.1101/2022.06.15.496275

Dermal nerve growth factor is increased in prurigo nodularis compared to atopic dermatitis

Deng, J.·Parthasarathy, V.·Bordeaux, Z.·Marani, M.·Lee, K.·Trinh, C.·Sutaria, N.·Cornman, H.·Kambala, A.·Pritchard, T.·Chen, S.·Oladipo, O. O.·Kwatra, M. M.·Alphonse, M. A.·Kwatra, S. G.

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Abstract

BackgroundPrurigo 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. ObjectiveTo determine the inflammatory, neuropathic, and structural pathways in PN compared to atopic dermatitis (AD). MethodsLesional 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 Students t-test and Mann-Whitney U. ResultsCompared to lesional AD, lesional PN had greater mRNA expression of MMPs, OSM, NGF, IL1{beta}, 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). LimitationsSingle, tertiary care center. ConclusionsPN 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.

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Deng, J., Parthasarathy, V., Bordeaux, Z., Marani, M., Lee, K., Trinh, C., Sutaria, N., Cornman, H., Kambala, A., Pritchard, T., Chen, S., Oladipo, O. O., Kwatra, M. M., Alphonse, M. A., Kwatra, S. G.. 2022-06-17. Dermal nerve growth factor is increased in prurigo nodularis compared to atopic dermatitis. https://doi.org/10.1101/2022.06.15.496275

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