Assuntos
Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Humanos , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/patologia , Pele/patologia , Administração Cutânea , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Análise de Sequência de RNA , Microambiente Tumoral/genéticaRESUMO
Dupilumab is a therapeutic antibody targeting IL-4 and IL-13 receptor subunit alpha used for the treatment of patients with atopic dermatitis (AD). Cases of psoriasis-like reactions induced under dupilumab treatment (dupilumab-induced psoriatic eruption [DI-Pso]) for AD were recently reported. To understand the pathogenesis of DI-Pso, we performed gene expression profiling studies on skin biopsies of DI-Pso (n = 7) compared with those of plaque psoriasis, AD, and healthy controls (n = 4 each). Differential gene expression was performed using enrichment and Gene Ontology analysis. Gene expression was validated by qPCR, and protein levels were assessed by immunohistochemistry. Transcriptomic and protein analysis of DI-Pso compared with that of healthy controls, plaque psoriasis, and AD skins revealed activation of T helper 17/IL-23 pathways associated with a significant expression of IL-36, surrogate marker of pustular psoriasis. By contrast, T helper 2 representative genes' expression was strongly decreased in DI-Pso across comparison. Matching analysis with public data of pustular psoriasis skin corroborated that DI-Pso and pustular psoriasis upstream regulators overlap, greater than the overlap with plaque psoriasis. Furthermore, DI-Pso showed strongly decreased expression of many barrier skin genes compared with healthy controls, plaque psoriasis, and AD. Our data indicate that the pathogenesis of DI-Pso relied on a shift of skin immune responses from a T helper 2 to an IL-36 and T helper 17 polarization and on intensified skin barrier alterations.
Assuntos
Dermatite Atópica , Exantema , Psoríase , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/genética , Interleucina-4/genética , Interleucina-13/genética , Psoríase/tratamento farmacológico , Psoríase/genéticaAssuntos
Dermatite Alérgica de Contato , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Nigella sativa , Administração Tópica , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Humanos , Óleos de Plantas/efeitos adversosRESUMO
Cutaneous involvement of chronic graft-versus-host disease (cGVHD) has a wide range of manifestations including a lichenoid form with a currently assumed mixed Th1/Th17 signature and a sclerotic form with Th1 signature. Despite substantial heterogeneity of innate and adaptive immune cells recruited to the skin and of the different clinical manifestations, treatment depends mainly on the severity of the skin involvement and relies on systemic, high-dose glucocorticoids alone or in combination with a calcineurin inhibitor. We performed the first study using RNA sequencing to profile and compare the transcriptome of lichen planus cGVHD (n = 8), morphea cGVHD (n = 5), and healthy controls (n = 6). Our findings revealed shared and unique inflammatory pathways to each cGVHD subtype that are both pathogenic and targetable. In particular, the deregulation of IFN signaling pathway was strongly associated with cutaneous cGVHD, whereas the triggering receptor expressed on myeloid cells 1 pathway was found to be specific of lichen planus and likely contributes to its pathogenesis. The results were confirmed at a protein level by performing immunohistochemistry staining and at a transcriptomic level using real-time quantitative polymerase chain reaction.
