DNA Copy Number Variation Associated with Anti-tumour Necrosis Factor Drug Response and Paradoxical Psoriasiform Reactions in Patients with Moderate-to-severe Psoriasis
Ancor Sanz-Garcia, Alejandra Reolid, Laura H. Fisas, Ester Muñoz-Aceituno, Mar Llamas-Velasco, Antonio Sahuquillo-Torralba, Rafael Botella-Estrada, Jorge García-Martínez, Raquel Navarro, Esteban Daudén, Francisco Abad-Santos, Maria C. Ovejero-Benito
DOI: 10.2340/00015555-3794
Abstract
Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30–50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study searched for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of anti-tumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.
Significance
Currently, 30–50% of patients with psoriasis do not respond to anti-tumour necrotic factor drugs, moreover, some patients develop complications. The aim of this study was to determine biomarkers that can predict drug response and complications, such as psoriasiform reactions. Bioinformatic tools were used to compare sections of the genome that are repeated (copy number variations), which could contain genes. Copy number variations were identified that could predict response to adalimumab. Moreover, copy number variations were found that could predict the development of psoriasiform reactions. These results may enable therapies to be improved. The biomarkers may help clinicians to avoid complications derived from anti-tumour necrotic factor drugs, and to optimize patients’ care.
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