Background/Purpose: Up to 30% of patients with psoriasis develop psoriatic arthritis (PsA). The traditional assumption is that the skin disease is the same in both conditions, although a previous proteomic analysis found differences[1]. The aim of this project was to investigate and compare the skin transcriptome in PsA and psoriasis.

Methods: Full thickness skin biopsies were obtained from healthy controls (HC) and paired lesional and uninvolved skin from patients with PsA. Libraries for bulk RNA sequencing were prepared from polyA selected RNA and sequenced on NovaSeq 6000. Sequencing data were analysed using Searchlight2. Read counts of HC, lesional and uninvolved skin from patients with psoriasis without PsA obtained by Tsoi et al 2019 [2](GEO accession GSE121212) were analysed using Searchlight2. Results from the two analyses were compared. Read counts of patients with PsA from the Tsoi cohort were used for validation.

Results: The PsA cohort had 9 participants and the psoriasis cohort 16 participants in each group. The Tsoi PsA cohort had 4 participants. Both PsA skin lesions (PsA L) and psoriasis skin lesions (PsO L) formed distinct populations in the respective principal component analysis plot. While the HC and PsA uninvolved skin (PsA U) populations were mixed, the psoriasis uninvolved skin (PsO U) population was skewed from the HC population toward the PsO L population. Consistent with this, there were 15 differentially expressed genes between the PsA U and HC groups, and 124 differentially expressed genes between the PsO U and HC groups. All but one overlapped with genes differentially expressed in PsO L versus HC and pathway analysis showed enrichment of pathways also enriched in PsO L.

In lesional skin, most enriched pathways were shared between PsA L and PsO L. However, PsA L skin was enriched in immunoglobulin genes while PsO L skin was not. Increased expression of immunoglobulin genes was also seen in PsA L skin in the Tsoi cohort.

Conclusion: This study found differences in the transcriptomes of psoriasis and PsA skin. PsA U skin is closer to healthy skin than PsO U skin, which shares some transcriptomic changes with PsO L skin. Although PsA L and PsO L skin share many inflammatory pathways, transcriptomic changes suggest differences in immunoglobulin pathways.

1. Cretu, D., et al., Clin Proteomics, 2015. 12(1): p. 1.
2. Tsoi, L.C., et al., J Invest Dermatol, 2019. 139(7): p. 1480-1489.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/psoriatic-arthritis-skin-is-transcriptionally-different-to-psoriasis-skin-and-enriched-in-immunoglobulin-transcripts/