Anais brasileiros de dermatologia · 2025
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.
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Canabrava Paola Borges Eckstein, Beauge Roll Stanley, Azouz Samir de Figueiredo, Timbó Renata Velozo, Martins Luciana Pereira Freire, Rodrigues Bruna Côrtes, Santos Naiara Daris Dos, Medeiros Marcella Palhano, de Araújo Andréa Monteiro, Santos Agenor de Castro Moreira Dos, Araújo Carla Nunes de, Nóbrega Otávio de Toledo, Kurizky Patrícia Shu, Mota Licia Maria Henrique da, Gomes Ciro Martins
Аннотация
BACKGROUND: 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.
OBJECTIVE: The authors aimed to determine the associations of specific Peripheral Blood Mononuclear Cell (PBMC) endotypic profiles with loss of treatment response in psoriasis patients.
METHODS: 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.
RESULTS: 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.
STUDY LIMITATIONS: 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.
CONCLUSIONS: The present study suggests an association between multiple TYK2 pathway markers and loss of systemic treatment response.
OBJECTIVE: The authors aimed to determine the associations of specific Peripheral Blood Mononuclear Cell (PBMC) endotypic profiles with loss of treatment response in psoriasis patients.
METHODS: 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.
RESULTS: 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.
STUDY LIMITATIONS: 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.
CONCLUSIONS: The present study suggests an association between multiple TYK2 pathway markers and loss of systemic treatment response.