DNA Copy Number Variation Associated with Anti-tumour Necrosis Factor Drug Response and Paradoxical Psoriasiform Reactions in Patients with Moderate-to-severe Psoriasis

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 antitumour 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.

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

“…Conversely, in the study by Cabaleiro et al ( n = 161, Spain), the following SNPs were associated with PP development in psoriasis patients under anti-TNF-α: the rs11209026 IL23R , rs10782001 FBXL19 , rs3087243 CTLA4 , rs651630 SLC2A8 , and rs1800453 TAP1 genes [ 115 ]. CNVs in regions involving the ARNT2 , LOC101929586, and MIR5572 genes have also been associated with the development of PP under infliximab or etanercept in a Spanish study ( n = 70) [ 116 ].…”

Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review

“…Among the 161 Caucasian patients, the polymorphism rs10782001 in FBXL19 and rs11209026 in IL23R may contribute to an increased risk of the secondary development of psoriasiform reactions owing to TNF blocking. In addition, in 70 Spanish patients, the copy number variation (CNV) harboring three genes (ARNT2, LOC101929586, and MIR5572) was related to the occurrence of paradoxical psoriasiform reactions at 3 and 6 months ( p = 0.006) [ 60 ]. In contrast, the presence of rs3087243 in CTLA4 , rs651630 in SLC12A8 , or rs1800453 in TAP1 was related to protection against psoriasiform lesions [ 61 ].…”

“…CPM (Carboxypeptidase M) is involved in the maturation of macrophages in psoriasis pathogenesis [ 67 ]. The CNV of the CPM gene was significantly associated with adalimumab response among 70 Spanish patients (PASI75 at 3 and 6 months, p < 0.05) [ 60 ].…”

Paradoxical psoriasis: The flip side of idiopathic psoriasis or an autocephalous reversible drug reaction?

“…Moderate-to-high anti-nuclear antibody titers and extensive pustular presentations may be negative prognostic indicators in PP patients [ 79 ]. DNA copy number variations may be a candidate marker to predict response to adalimumab and the development of PP [ 80 , 81 ].…”