OP0203 CHARACTERIZING THE EPIGENOMIC LANDSCAPE OF PSORIASIS PATIENTS DESTINED TO DEVELOP PSORIATIC ARTHRITIS

Abstract

Background Approximately 30% of psoriasis patients develop psoriatic arthritis (PsA), typically within 10 years of psoriasis onset. A large proportion of individuals with PsA remain undiagnosed. Epigenetics is potentially a major mechanism through which environmental factors influence PsA risk. An understanding of how the epigenome changes during the transition to PsA could yield predictive biomarkers and facilitate PsA diagnosis. We hypothesize that epigenetic deregulation at the level of DNA methylation occurs early in PsA pathogenesis, prior to overt clinical symptoms, and epigenetic marks can be used as biomarkers for disease prediction. Objectives To discover predictive biomarkers of PsA and gain an understanding of the pathogenesis of PsA by characterizing the epigenomic landscape of psoriasis patients who later developed PsA (converters) and comparing it to psoriasis patients who did not develop PsA (non-converters). Methods We performed an epigenome-wide comparison of DNA methylation in baseline whole blood samples from psoriasis converters (n=60) and non-converters (n=60) from a longitudinal cohort. Converters and non-converters were matched for age, sex, psoriasis duration, and duration of follow-up. DNA was analyzed on Human MethylationEPIC BeadChips using the ChAMP package. Cell type heterogeneity was corrected using RefbaseEWAS. Differentially methylated probes and regions were identified using limma and DMRcate, respectively. The FEM package was used to infer differentially methylated gene modules within a protein-protein interaction network. Results Converter baseline samples were collected a median of 4.2 (interquartile range 1.9-6.3) years prior to the onset of PsA, while non-converters samples were collected a median of 4.3 (1.2-7.3) years prior to the most recent clinic visit. The RefbaseEWAS method estimated that converters had slightly higher proportions of CD4+ T cells and granulocytes compared to non-converters, however the differences were not statistically significant. After adjustment for cell type heterogeneity, 68 individual CpG sites were found to be differentially methylated between converters and non-converters (FDR Conclusion Changes in individual CpGs, DMRs, and inflammatory pathways were detected in baseline samples of psoriasis converters compared to non-converters. These preliminary data support our hypothesis that DNA methylation changes occur early in PsA pathogenesis and can potentially serve as prognostic biomarkers of future onset of arthritis in psoriasis patients. Disclosure of Interests Remy Pollock: None declared, Rohan Machhar: None declared, Vinod Chandran: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB