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  • Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjögren's syndrome

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Basic and translational research
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Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjögren's syndrome
  1. Amandine Charras1,
  2. Orsia D Konsta1,2,
  3. Christelle Le Dantec1,
  4. Cristina Bagacean1,3,
  5. Efstathia K Kapsogeorgou2,
  6. Athanasios G Tzioufas2,
  7. Jacques-Olivier Pers1,
  8. Anne Bordron1,
  9. Yves Renaudineau1,3
  1. 1INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France
  2. 2Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
  3. 3Laboratory of Immunology and Immunotherapy, Brest University Medical School, CHRU Morvan, Brest, France
  1. Correspondence to Professor Yves Renaudineau, Laboratory of Immunology and Immunotherapy, Brest University Medical School, CHRU Morvan BP824, Brest F29609, France; yves.renaudineau{at}univ-brest.fr

Abstract

Objectives The aetiology of primary Sjögren's syndrome (pSS), also referred to as autoimmune epithelitis, is incompletely understood but includes an epigenetic contribution. Accordingly, the aim of this study was to investigate DNA methylation in salivary gland epithelial cells (SGEC), and to compare results with those publicly available from pSS B and T cells.

Methods Long-term cultured SGEC were selected to conduct an epigenome-wide association study (EWAS) in patients with pSS with comparison to controls using the HumanMethylation 450 K array from Illumina.

Results The analysis of differentially methylated CpG (DMC) uncovered 4662 positions corresponding to 2560 genes, and 575 genes with two or more DMC sites (DMCs), in SGEC as compared with controls. Further analysis highlighted an important proportion of interferon-regulated genes (61%), the calcium pathway (hypomethylated) and the Wnt pathway (hypermethylated). When comparing SGEC with pSS T and/or B cell results, an important overlap was observed with respect to differentially methylated genes (38.8%) and pSS risk factors (71.4%), although such assertion was not true when comparing DMCs.

Conclusions This study conducted in SGEC emphasises the role of DNA methylation in pSS pathogenesis and supports the necessity to conduct pure cell analysis for future EWAS studies when analysing salivary glands from patients with pSS.

  • Autoimmunity
  • Sjøgren's Syndrome
  • Gene Polymorphism

https://doi.org/10.1136/annrheumdis-2016-210167

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    Footnotes

    • Handling editor Tore K Kvien

    • AB and YR are the last two senior authors contributed equally to this work.

    • Contributors AC, ODK, CLD, CB, AB and YR analysed the data, drafted and revised the paper. EKK, AGT, J-OP and YR initiated the collaborative project and revised the project. ODK, EKK and AGT collected patient material and clinical data.

    • Funding Research Accounts of the University of Athens (9988).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval The institutional review board at the University of Athens.

    • Provenance and peer review Not commissioned; externally peer reviewed.