title: Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus.
abstract: Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known. Serum samples from autoimmune (NZBxNZW)F1 mice, healthy BALB/c mice, patients with SLE, RA and normal healthy individuals were analyzed for presence and amount of circulating anti-dsDNA antibodies and nucleosomal DNA. Here we use a quantitative PCR to measure circulating DNA in sera. We demonstrate an inverse correlation between anti-dsDNA antibodies and the DNA concentration in the circulation in both murine and human serum samples. High titer of anti-DNA antibodies in human sera correlated with reduced levels of circulating chromatin, and in lupus prone mice with deposition within glomeruli. The inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect the development of lupus nephritis at an early stage.
authors.affiliation: Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Mariann H
authors.initials: MH
authors.lastname: Jørgensen
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Rekvig
authors.forename: Rasmus S
authors.initials: RS
authors.lastname: Jacobsen
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Fenton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D015415:Biomarkers / Q000032:analysis / Q000097:blood*; D016022:Case-Control Studies; D002843:Chromatin / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005920:Glomerular Mesangium / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008181:Lupus Nephritis / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008875:Middle Aged; D009707:Nucleosomes / Q000737:chemistry / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D015415:Biomarkers; D002843:Chromatin; D009707:Nucleosomes; D004247:DNA