Differences in transcriptional changes in psoriasis and psoriatic arthritis skin with immunoglobulin gene enrichment in psoriatic arthritis

Johnsson, H., Cole, J., McInnes, I. B. , Graham, G. and Siebert, S. (2023) Differences in transcriptional changes in psoriasis and psoriatic arthritis skin with immunoglobulin gene enrichment in psoriatic arthritis. Rheumatology, (doi: 10.1093/rheumatology/kead195) (PMID:37137278) (Early Online Publication)

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Abstract

Objectives: ∼20% of people with psoriasis develop psoriatic arthritis (PsA). Although genetic, clinical, and environmental risk factors have been identified, it is not known why some people with psoriasis develop PsA. The skin disease is traditionally considered the same in both. This study compares transcriptional changes in psoriasis and PsA skin for the first time. Methods: Skin biopsies were collected from healthy control (HC), and uninvolved and lesional skin from patients with PsA. Bulk tissue sequencing was performed and analysed using the pipeline Searchlight 2.0. Transcriptional changes in PsA skin were compared with existing sequencing data from participants with psoriasis without PsA (GSE121212). Psoriasis and PsA datasets could not be directly compared as different analysis methods were used. Data from participants with PsA in the GSE121212 dataset were used for validation. Results: Skin samples from nine participants with PsA and nine HC were sequenced, analysed, and compared with available transcriptomic data for 16 participants with psoriasis compared with 16 HC. Uninvolved skin in psoriasis shared transcriptional changes with lesional skin in psoriasis, but uninvolved skin in PsA did not. Most transcriptional changes in psoriasis and PsA lesional skin were shared, but immunoglobulin genes were upregulated in PsA lesional skin specifically. The transcription factor POU2F1, which regulates immunoglobulin gene expression, was enriched in PsA lesional skin. This was confirmed in the validation cohort. Conclusions: Immunoglobulin genes are upregulated in PsA but not in psoriasis skin lesions. This may have implications for the spread from the cutaneous compartment to other tissues.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Siebert, Professor Stefan and Cole, Mr John and Johnsson, Dr Hanna and Graham, Professor Gerard
Authors: Johnsson, H., Cole, J., McInnes, I. B., Graham, G., and Siebert, S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Rheumatology
Publisher:Oxford University Press
ISSN:1462-0324
ISSN (Online):1462-0332
Published Online:03 May 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Rheumatology 2023
Publisher Policy:Reproduced under a Creative Commons License

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