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The deregulation of NOTCH pathway, inflammatory cytokines, and keratinization genes in two Dowling–Degos disease patients with hidradenitis suppurativa
Author(s) -
Penha Ricardo,
Cortez de Almeida Rita Fernanda,
Mariz Juliana,
Lisboa Lilian,
Barbosa Lívia,
da Silva Roberto
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61800
Subject(s) - hidradenitis suppurativa , downregulation and upregulation , proinflammatory cytokine , notch signaling pathway , context (archaeology) , medicine , gene , immunology , adalimumab , cancer research , tumor necrosis factor alpha , disease , inflammation , biology , pathology , genetics , paleontology
Dowling–Degos disease (DDD) is a rare autosomal‐dominant genodermatosis and it has been associated with hidradenitis suppurativa (HS). Deregulation of NOTCH pathway has been linked to the development of HS in DDD context (DDD‐HS). However, molecular alterations in DDD‐HS, including altered gene expression of NOTCH and downstream effectors that are involved in the follicular differentiation and inflammatory response, are poorly defined. We report two cases of patients diagnosed with DDD‐HS, one of those, under Adalimumab treatment. Our results have shown downregulation of NOTCH1/NCSTN pathway, distinct molecular profiles of inflammatory cytokines ( IL23A and TNF ), and a novel aberrant upregulation of genes involved in the cornified envelope (CE) formation ( SPRR1B , SPRR2D , SPRR3, and IVL ) in paired HS lesions of two DDD patients.