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Narrow-band UVB phototherapy for psoriasis

ABSTRACT: Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53431 | GEO | 2013/12/23

SECONDARY ACCESSION(S): PRJNA231980

REPOSITORIES: GEO

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Project description:Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques. Twelve patients diagnosed with plaque type psoriasis were recruited to the study. NB-UVB irradiation was administered to the whole body two to three times a week. Treatment comprising approximately 24 sessions was given during two to three months. A total of six 4 mm diameter punch biopsies were taken from lesions on each psoriasis patient: two prior to UV treatment (pre-UV), two at the middle stage of UV treatment (after about one month of treatment, mid-UV) and two before the last treatment session (post-UV). Twelve healthy age-, sex- and skin type-matched volunteers were also recruited and two punch biopsies were taken from the buttocks. RNA was extracted from Laser capture microdissected epidermis.

Project description:Phototherapy is an effective therapy and may induce remission of psoriasis. Previous studies have established the action spectrum of clearance and that apoptosis is differentially induced in psoriasis plaques by clinically effective wavelengths of ultraviolet B (UVB). The aim of this study was to investigate the molecular mechanisms regulating psoriasis plaque resolution by studying the transcriptomic response to clinically effective (311nm, narrow band) UVB compared to a clinically ineffective (290nm) wavelength. We irradiated lesional psoriatic skin in vivo with a single 3 MED (minimal erythemal dose) of 311nm or 290nm wavelength of UVB and performed skin biopsies at 4h or 18h post irradiation and from un-irradiated lesional skin. Forty-eight micro-dissected epidermal samples were analysed using the Illumina DASL array platform from 20 psoriatic patients. Bioinformatic analysis identified differentially expressed genes (DEGs) associated with 311nm but not 290nm irradiation; these DEGs were subject to Ingenuity pathway and upstream regulator analysis. The number of differentially regulated epidermal genes was greatest at 18h following UVB, after irradiation with clinically effective (311nm) UVB. The main pathways differentially affected by 311nm UVB only were apoptosis, necrosis, acute phase signalling, p53 signalling and chemotaxis. The greatest fold change observed was a 7.5 fold increase in expression of CDKN1A (WAF1/ p21), the p53 target gene, following irradiation with 311nm UVB but not 290nm (clinically ineffective UVB). Acute phase, LXR and PTEN signalling, dendritic cell maturation, granulocyte adhesion and atherosclerotic pathways were also differentially regulated by 311nm compared to 290nm UVB. This work provides insight into the molecular mechanisms regulating psoriatic remodelling in response to UV phototherapy, supports a key role for apoptosis and cell death in psoriasis plaque clearance, and identifies a number of novel therapeutic pathways. Further studies may lead to development of potential biomarkers to assess which patients are more likely to respond to UVB.

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Narrow-band UVB phototherapy for psoriasis

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