title: Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjögren's syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Charras
authors.affiliation: INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France.|Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece.
authors.forename: Orsia D
authors.initials: OD
authors.lastname: Konsta
authors.affiliation: INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Le Dantec
authors.affiliation: INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France.|Laboratory of Immunology and Immunotherapy, Brest University Medical School, CHRU Morvan, Brest, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bagacean
authors.affiliation: Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece.
authors.forename: Efstathia K
authors.initials: EK
authors.lastname: Kapsogeorgou
authors.affiliation: Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Tzioufas
authors.affiliation: INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Pers
authors.affiliation: INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bordron
authors.affiliation: INSERM U1227 B lymphocytes and autoimmunity, Labex IGO, Réseau épigénétique et réseau canaux ioniques du cancéropole Grand Ouest, Université de Brest, Brest, France.|Laboratory of Immunology and Immunotherapy, Brest University Medical School, CHRU Morvan, Brest, France.
authors.forename: Yves
authors.identifier: http://orcid.org/0000-0001-5098-5002
authors.initials: Y
authors.lastname: Renaudineau
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000235:genetics; D008875:Middle Aged; D012469:Salivary Glands / Q000166:cytology; D012859:Sjogren's Syndrome / Q000235:genetics*; D013601:T-Lymphocytes; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000235:genetics; D055815:Young Adult
chemical_list: D007372:Interferons; D002118:Calcium
keywords: Autoimmunity; Gene Polymorphism; Sjøgren's Syndrome