Sanz-Garcia Ancor, Reolid Alejandra, Fisas Laura H, Muñoz-Aceituno Ester, Llamas-Velasco Mar, Sahuquillo-Torralba Antonio, Botella-Estrada Rafael, García-Martínez Jorge, Navarro Raquel, Daudén Esteban, Abad-Santos Francisco, Ovejero-Benito Maria C
Data Analysis Unit, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, Spain.
Acta Derm Venereol. 2021 May 4;101(5):adv00448. doi: 10.2340/00015555-3794.
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 search-ed 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.
靶向肿瘤坏死因子的生物药物对银屑病有效。然而,30%至50%的患者对这些药物无反应,甚至可能出现矛盾性银屑病样反应。本研究寻找可预测抗肿瘤坏死因子药物反应或抗肿瘤坏死因子诱导的银屑病样反应出现的DNA拷贝数变异。从70例接受抗肿瘤坏死因子药物治疗的中重度斑块状银屑病患者中采集外周血样本。样本用Illumina 450K甲基化微阵列进行分析。使用conumee和芯片分析甲基化管道(ChAMP)R包从原始甲基化数据中获得拷贝数变异。发现一个拷贝数变异,包含一个与阿达木单抗反应显著相关的基因(CPM)(Bonferroni校正p值<0.05)。此外,鉴定出一个拷贝数变异,包含3个与矛盾性银屑病样反应发生相关的基因(ARNT2、LOC101929586和MIR5572)。总之,本研究已鉴定出DNA拷贝数变异,这些变异可能是预测对阿达木单抗反应及抗肿瘤坏死因子矛盾性银屑病样反应发生的良好候选标志物。