title: [Activation of hypomethylated DNA on plasmacytoid dendritic cells in patients with systemic lupus erythematosus].
abstract: OBJECTIVE
  To explore the activation of hypomethylated DNA on plasmacytoid dendritic cells (pDC) in patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of SLE patients and healthy controls. The methylation level of DNA and the expression of DNA methyltransferase 1 (DNMT1) mRNA were detected. Flow cytometry was used to detect the expression of CD32 on pDC and the serum concentration of interferon-alpha (IFN-α) measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The DNA methylation level from SLE patients (1.4 ± 0.6) % was lower than that of controls (1.8 ± 0.7) % (P < 0.01). The expression of DNMT1 mRNA significantly decreased in SLE patients (0.06 ± 0.03) versus the controls (0.09 ± 0.02) (P < 0.01). The CD32 expression on pDC from SLE patients (29 ± 19)% was higher than that from controls (18.02 ± 7.80)% (P < 0.01). The serum level of IFN-α in SLE patients (4.5 ± 6.7) ng/L was significantly higher than that of controls (2.1 ± 2.0) ng/L (P < 0.01). The methylation level of DNA in SLE patients was positively correlated with the expression of DNMT1 mRNA (r = 0.257, P < 0.05) and negatively with the expression of CD32 (r = -0.358, P < 0.01) and IFN-α (r = -0.280, P < 0.05).
  
  
  CONCLUSIONS
  The methylation level of genomic DNA decreases in SLE patients due to the down-regulated expression of DNMT1 gene. Hypomethylated DNA may be translocated intracellularly via endocytic receptor (CD32) on pDC. And the activation of pDC is induced to produce IFN-α so as to participate in the onset of SLE.
authors.affiliation: Department of Rheumatology & Immunology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: Department of Rheumatology & Immunology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China. Email: gswang0551@163.com.
authors.forename: Guo-sheng
authors.initials: GS
authors.lastname: Wang
authors.affiliation: Department of Rheumatology & Immunology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Xiang-pei
authors.initials: XP
authors.lastname: Li
authors.affiliation: Department of Rheumatology & Immunology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Rheumatology & Immunology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.
authors.forename: Long
authors.initials: L
authors.lastname: Qian
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D017452:Receptors, IgG / Q000378:metabolism; D055815:Young Adult
chemical_list: D016898:Interferon-alpha; D012333:RNA, Messenger; D017452:Receptors, IgG; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human