# Evaluation of Tyrosine Kinase-2 (TYK2) signaling pathway gene expression and the presence of the single-nucleotide polymorphism rs12720356 in the peripheral blood of patients with severe psoriasis and loss of systemic treatment response

## TL;DR

This study explores how gene expression in the TYK2 pathway and a specific genetic variant relate to treatment response in severe psoriasis patients.

## Contribution

The study identifies a cluster of patients with upregulated TYK2-dependent mediators and a genetic variant linked to poor treatment outcomes.

## Key findings

- TYK2 was upregulated in PBMCs of patients with PASI > 10, but results were highly variable.
- A cluster of 19 patients showed increased TYK2-dependent mediators and worse clinical outcomes.
- Three patients had the TYK2I684S variant, suggesting a potential genetic link to treatment resistance.

## Abstract

RNA sequencing-based studies have identified the transcription processes that contribute to psoriasis development, but the associations of these processes with specific phenotypes need further investigation.

The authors aimed to determine the associations of specific Peripheral Blood Mononuclear Cell (PBMC) endotypic profiles with loss of treatment response in psoriasis patients.

A Psoriasis Area and Severity Index (PASI) > 10 was the main outcome. The gene expression of Tyrosine Kinase-2 (TYK), Interleukin (IL)-12A, IL-12B, IL-23A, IL-23 Receptor (IL-23R), IL-6, IL-6R,IL-17A and Tumor Necrosis Factor (TNF) in PBMCs was quantified as possible risk factors. Single-Nucleotide Polymorphisms (SNP) were screened using a genotyping technique. Hierarchical clustering of the gene expression results was performed.

The authors included 178 psoriasis patients. TYK2 was upregulated in the PBMCs of patients with a PASI score > 10, but its distribution was widely variable. A cluster of 19 patients exhibited upregulated expression of most TYK2-dependent mediators and increased PASI (p = 0.021) and Dermatology Life Quality Index (DLQI) scores (p = 0.034). Three patients harbored the TYK2I684S variant.

The utility of using single markers for psoriasis diagnosis is limited due to the wide variability of results, but the utility of the simultaneous evaluation of a set of markers has promise.

The present study suggests an association between multiple TYK2 pathway markers and loss of systemic treatment response.