Background/Purpose: Psoriatic disease is a chronic inflammatory disorder spanning from skin disease (PsO) to psoriatic arthritis (PsA) without known serum biomarkers. The genetic background is insufficient to explain disease onset as illustrated by monozygotic (MZ) twins and epigenetics may contribute to disease susceptibility modulating gene expression. We analyzed the DNA methylation, transcriptome, and proteomic profile in MZ twins discordant for PsO/PsA.

Methods: MZ twin couples discordant and concordant for PsO/PsA were investigated for (1) genome-wide DNA methylation (Infinium MethylationEPIC BeadChip), (2) RNA and transcriptome (Illumina TruSeq Stranded mRNA kit), and (3) proteomics using aptamers (SOMAlogic).Results observed with aptamers were further validated by ELISA.

Results: The epigenetic analysis identified 19 genes consistently differentially methylated and mostly involved in the pathway of TGF-β and IFN response. Pathway analysis of integrated DNA methylation and transcriptome demonstrated an enrichment in “transcription regulation”, “innate immunity”, “ATP-binding” and, “Srp-dependent co-translational proteins”, that may be involved in the psoriatic condition. Serum proteomics reported a significant up- and downregulation of 10 and 3 proteins, respectively, largely involved in the innate and adaptive immune response, DNA repair and DNA damage sensors. Validation results showed a significant correlation between the SOMAlogic and ELISA tests for 2 proteins (respectively r=0.70, p=0.02, and r=0.50, p=0.04) and we confirmed that levels of 3 proteins involved in the regulation of UV radiation-induced apoptosis and in the cutaneous inflammatory response were elevated in sera from psoriatic disease patients, albeit not significantly, and one protein involved in hematopoietic and dendritic cell differentiation and apoptosis was significantly more expressed in both Pso and PsA compared to controls (HC n=2, 20%, Pso+PsA n=18, 60%, p=0.028; Pso n=10, 66.7%, p=0.02).

Conclusion: We report the first -omics approach in MZ twins discordant for psoriatic disease and suggest that the observed changes may constitute diasease biomarkers and point to biological pathways with a potential pathogenic role.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/genome-wide-dna-methylation-transcriptomics-and-proteomics-of-psoriasis-and-psoriatic-arthritis-in-monozygotic-twins/