{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T23:29:16Z","timestamp":1764458956176,"version":"3.41.2"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso\/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP\u2014qPCR was used to confirm specific signals. Data were replicated in an independent cohort of seven patients with Pso\/PsA and 3 healthy controls. Transcriptomic profiling was performed by RNAsequence on the same 7 monozygotic twin pairs.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1\u00a0kb of distance and significant within-pair \u0394<jats:italic>\u03b2<\/jats:italic>-values (<jats:italic>p<\/jats:italic> &amp;lt; 0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-\u03b2 signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6\/JAK\/STAT3 and TNF-\u03b1 pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients\u2019 immune cells, characteristic of pro-inflammatory T lymphocytes.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.<\/jats:p>","DOI":"10.3389\/fcell.2021.778677","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:23:49Z","timestamp":1638314629000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["DNA Methylation Signature in Monozygotic Twins Discordant for Psoriatic Disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Matteo","family":"Vecellio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvezia Maria","family":"Paraboschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Ceribelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasa","family":"Isailovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Motta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Cardamone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Robusto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Asselta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Brescianini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Sacrini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Costanzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"De Santis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Antonietta","family":"Stazi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Duga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Selmi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e1003678","DOI":"10.1371\/journal.pgen.1003678","article-title":"Genome-wide DNA Methylation Analysis of Systemic Lupus Erythematosus Reveals Persistent Hypomethylation of Interferon Genes and Compositional Changes to CD4+ T-Cell Populations","volume":"9","author":"Absher","year":"2013","journal-title":"Plos Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1093\/bioinformatics\/btl140","article-title":"Improved Scoring of Functional Groups from Gene Expression Data by Decorrelating GO Graph Structure","volume":"22","author":"Alexa","year":"2006","journal-title":"Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1101\/2020.01.23.912717","article-title":"In Silico Modeling of Metabolic State in Single Th17 Cells Reveals Novel Regulators of Inflammation and Autoimmunity","author":"Allon Wagner","year":"2020","journal-title":"bioRxiv"},{"key":"B4","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/exd.12128","article-title":"Studies of Jak\/STAT3 Expression and Signalling in Psoriasis Identifies STAT3-Ser727 Phosphorylation as a Modulator of Transcriptional Activity","volume":"22","author":"Andr\u00e9s","year":"2013","journal-title":"Exp. 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