title: Overlap between differentially methylated DNA regions in blood B lymphocytes and genetic at-risk loci in primary Sjögren's syndrome.
abstract: BACKGROUND
  Beyond genetics, epigenetics alterations and especially those related to DNA methylation, play key roles in the pathogenesis of autoimmune diseases such as primary Sjögren's syndrome (pSS) and systemic lupus erythematosus. This study aimed to assess the role of methylation deregulation in pSS pathogeny through a genome-wide methylation approach.
  
  
  METHODS
  26 female patients with pSS and 22 age-matched controls were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and their genome-wide DNA methylation profiles were analysed using Infinium Human Methylation 450 K BeadChips. Probes with a median DNA methylation difference of at least 7% and p<0.01 between patients and controls were considered significantly differentially methylated.
  
  
  RESULTS
  Methylation alterations were mainly present in B cells compared with T cells. In B cells, an enrichment of genes with differentially methylated probes in genetic at-risk loci was observed, suggesting involvement of both genetic and epigenetic abnormalities in the same genes. Methylation alterations in B cells were more frequent in some specific pathways including Interferon Regulated Genes, mainly among patients who were autoantibody positive. Moreover, genes with differentially methylated probes were over-represented in B cells from patients with active disease.
  
  
  CONCLUSIONS
  This study demonstrated more important deregulation of DNA methylation patterns in B cells compared with T cells, emphasising the importance of B cells in the pathogenesis of the disease. Overlap between genes with differentially methylated probes in B lymphocytes and genetic at-risk loci is a new finding highlighting their importance in pSS.
authors.affiliation: Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, AP-HP, Institut National de la Santé et de la Recherche Médicale (INSERM) U1184, Center for immunology of viral infections and autoimmune diseases, Le Kremlin Bicêtre, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Miceli-Richard
authors.affiliation: Laboratory for Epigenetics and Environment, Centre National de Génotypage-CEA/Institut de Génomique, Evry, France CEA, IDMIT Center, DSV/iMETI, INSERM U1184, Fontenay-aux-Roses, France.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Wang-Renault
authors.affiliation: Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, AP-HP, Institut National de la Santé et de la Recherche Médicale (INSERM) U1184, Center for immunology of viral infections and autoimmune diseases, Le Kremlin Bicêtre, France.
authors.forename: Saida
authors.initials: S
authors.lastname: Boudaoud
authors.affiliation: Laboratory for Epigenetics and Environment, Centre National de Génotypage-CEA/Institut de Génomique, Evry, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Busato
authors.affiliation: Laboratory for Epigenetics and Environment, Centre National de Génotypage-CEA/Institut de Génomique, Evry, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lallemand
authors.affiliation: Laboratory for Epigenetics and Environment, Centre National de Génotypage-CEA/Institut de Génomique, Evry, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bethune
authors.affiliation: Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, AP-HP, Institut National de la Santé et de la Recherche Médicale (INSERM) U1184, Center for immunology of viral infections and autoimmune diseases, Le Kremlin Bicêtre, France.
authors.forename: Rakiba
authors.initials: R
authors.lastname: Belkhir
authors.affiliation: Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, AP-HP, Institut National de la Santé et de la Recherche Médicale (INSERM) U1184, Center for immunology of viral infections and autoimmune diseases, Le Kremlin Bicêtre, France.
authors.forename: Gaétane
authors.initials: G
authors.lastname: Nocturne
authors.affiliation: Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, AP-HP, Institut National de la Santé et de la Recherche Médicale (INSERM) U1184, Center for immunology of viral infections and autoimmune diseases, Le Kremlin Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Laboratory for Epigenetics and Environment, Centre National de Génotypage-CEA/Institut de Génomique, Evry, France.
authors.forename: Jörg
authors.initials: J
authors.lastname: Tost
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000276:immunology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology*
keywords: Autoantibodies; Autoimmune Diseases; B cells; Sjøgren's Syndrome; T Cells