DNA methylation patterns in CD4+ T-cells separate psoriasis patients from healthy controls, and skin psoriasis from psoriatic arthritis

Research output: Contribution to journalResearch articleContributedpeer-review


  • Valentina Natoli - , University of Liverpool (UOL) (Author)
  • Amandine Charras - , University of Liverpool (UOL) (Author)
  • Sigrun R. Hofmann - , Department of Paediatrics, University Hospital Carl Gustav Carus Dresden (Author)
  • Sarah Northey - , University of Liverpool (UOL) (Author)
  • Susanne Russ - , Department of Child and Adolescent Psychiatry and Psychotherapy (Author)
  • Felix Schulze - , Department of Paediatrics, University Hospital Carl Gustav Carus Dresden (Author)
  • Liza McCann - , Alder Hey Children's NHS Foundation Trust (Author)
  • Susanne Abraham - , Department of Dermatology, University Hospital Carl Gustav Carus Dresden (Author)
  • Christian M Hedrich - , University of Liverpool (UOL) (Author)


BACKGROUND: Psoriasis is an autoimmune/inflammatory disorder primarily affecting the skin. Chronic joint inflammation triggers the diagnosis of psoriatic arthritis (PsA) in approximately one-third of psoriasis patients. Although joint disease typically follows the onset of skin psoriasis, in around 15% of cases it is the initial presentation, which can result in diagnostic delays. The pathophysiological mechanisms underlying psoriasis and PsA are not yet fully understood, but there is evidence pointing towards epigenetic dysregulation involving CD4+ and CD8+ T-cells.

OBJECTIVES: The aim of this study was to investigate disease-associated DNA methylation patterns in CD4+ T-cells from psoriasis and PsA patients that may represent potential diagnostic and/or prognostic biomarkers.

METHODS: PBMCs were collected from 12 patients with chronic plaque psoriasis and 8 PsA patients, and 8 healthy controls. CD4+ T-cells were separated through FACS sorting, and DNA methylation profiling was performed (Illumina EPIC850K arrays). Bioinformatic analyses, including gene ontology (GO) and KEGG pathway analysis, were performed using R. To identify genes under the control of interferon (IFN), the Interferome database was consulted, and DNA Methylation Scores were calculated.

RESULTS: Numbers and proportions of CD4+ T-cell subsets (naïve, central memory, effector memory, CD45RA re-expressing effector memory cells) did not vary between controls, skin psoriasis and PsA patients. 883 differentially methylated positions (DMPs) affecting 548 genes were identified between controls and "all" psoriasis patients. Principal component and partial least-squares discriminant analysis separated controls from skin psoriasis and PsA patients. GO analysis considering promoter DMPs delivered hypermethylation of genes involved in "regulation of wound healing, spreading of epidermal cells", "negative regulation of cell-substrate junction organization" and "negative regulation of focal adhesion assembly". Comparing controls and "all" psoriasis, a majority of DMPs mapped to IFN-related genes (69.2%). Notably, DNA methylation profiles also distinguished skin psoriasis from PsA patients (2,949 DMPs/1,084 genes) through genes affecting "cAMP-dependent protein kinase inhibitor activity" and "cAMP-dependent protein kinase regulator activity". Treatment with cytokine inhibitors (IL-17/TNF) corrected DNA methylation patterns of IL-17/TNF-associated genes, and methylation scores correlated with skin disease activity scores (PASI).

CONCLUSION: DNA methylation profiles in CD4+ T-cells discriminate between skin psoriasis and PsA. DNA methylation signatures may be applied for quantification of disease activity and patient stratification towards individualized treatment.


Original languageEnglish
Article number1245876
Pages (from-to)1245876
JournalFrontiers in immunology
Publication statusPublished - 15 Aug 2023

External IDs

PubMedCentral PMC10472451
ORCID /0000-0001-7457-6481/work/142246232
WOS 001059693100001
Scopus 85169589281


ASJC Scopus subject areas


  • Humans, Arthritis, Psoriatic/diagnosis, Interleukin-17, DNA Methylation, CD8-Positive T-Lymphocytes, Psoriasis/genetics, Autoimmune Diseases, Cyclic AMP-Dependent Protein Kinases, CD4-Positive T-Lymphocytes, Biomarker, Psoriasis, Psoriatic arthritis, CD4(+) T-cell, Epigenetics, Interferon, Methylation

Library keywords