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Genomic profiling of the overlap phenotype between psoriasis and atopic dermatitis

ABSTRACT: Clinical overlaps between psoriasis and atopic dermatitis are sometimes undiscernible, and there is no consensus whether to treat the overlap phenotype as psoriasis or atopic dermatitis. We enrolled patients diagnosed with either psoriasis or atopic dermatitis, and clinically re-stratified them into classic psoriasis, classic atopic dermatitis, and the overlap phenotype between psoriasis and atopic dermatitis. We compared gene expression profiles of lesional and nonlesional skin biopsy tissues between the three comparison groups. Global mRNA expression and T-cell subset cytokine expression in the skin of the overlap phenotype were consistent with the profiles of psoriasis and different from the profiles of atopic dermatitis. Unsupervised k-means clustering indicated that the best number of distinct clusters for the total population of the three comparison groups was two, and the two clusters of psoriasis and atopic dermatitis were differentiated by gene expression. Our study suggests that clinical overlap phenotype between psoriasis and atopic dermatitis has dominant molecular features of psoriasis, and genomic biomarkers can differentiate psoriasis and atopic dermatitis at molecular levels in patients with a spectrum of psoriasis and atopic dermatitis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182740 | GEO | 2023/06/24

REPOSITORIES: GEO

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Project description:Recently, it was shown that lesional skin of atopic dermatitis patients expresses low levels of some antimicrobial peptides, compared with psoriasis patients. Here we performed microarray analysis on mRNA from purified lesional epidermal cells of patients with chronic plaque psoriasis and chronic atopic dermatitis, to investigate whether this is a general phenomenon for host defense proteins, and how specific it is for this class of molecules. We found overexpression of many antimicrobial genes in keratinocytes from psoriatic skin compared with atopic dermatitis skin. Interestingly, we observed that markers of normal differentiation and the activated/hyperproliferative epidermal phenotype were expressed at equal levels. Chronic lesions of psoriasis and atopic dermatitis patients are remarkably similar with respect to cellular proliferation. We conclude that psoriatic epidermis expresses high levels of host defense proteins compared with atopic dermatitis epidermis, and this phenomenon appears to be specific for these proteins. It remains to be investigated whether this is caused by genetic polymorphisms in pathways leading to an epidermal antimicrobial response, or by differences in the cellular infiltrate in psoriasis compared with atopic dermatitis. In general the microarray technique is used to probe a (very large) number of genes for say the deseased and the healthy state.Then gene ontology is used to detect the involved pathways.We did not set out to find a comprehensive list of genes involved in these skin deseases.We do suspect that the "path way" approach might be a bit anthropomorphic.Here we offered a different approach.We set out to investigate the evolutionary fitness changes from one local maximum , Psoriasis , to another , Atopie. Our hypothesis is that Psoriasis is at one extreme in the reaction of the evolution to invading micro organisms and Atopie at an other.So the vast chemical web called human being with numorous feedback and feed forward signals would then be tilted a bit in multidimensional Gene Space and the microarray technique would show us a glimpse of the involved genes. Keywords: Disease state analysis

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Genomic profiling of the overlap phenotype between psoriasis and atopic dermatitis

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