title: Anti-dsDNA-NcX ELISA: dsDNA-loaded nucleosomes improve diagnosis and monitoring of disease activity in systemic lupus erythematosus.
abstract: BACKGROUND
  The objective of this study was to compare the clinical usefulness of the new anti-double-stranded DNA nucleosome-complexed enzyme-linked immunosorbent assay (Anti-dsDNA-NcX ELISA), which is based on dsDNA-loaded nucleosomes as antigens, with established test systems based on dsDNA or nucleosomes alone for systemic lupus erythematosus (SLE) diagnostics and determination of disease activity.
  
  
  METHODS
  Sera from a cohort of 964 individuals comprising 207 SLE patients, 357 disease controls and 400 healthy donors were investigated using the Anti-dsDNA-NcX ELISA, Farr assay, Anti-dsDNA ELISA, Anti-nucleosome ELISA and Crithidia luciliae immunofluorescence (CLIF) assay, all of which are tests available from EUROIMMUN Medizinische Labordiagnostika AG (Lübeck, Germany). Receiver operating characteristic curve analyses were performed to compare the sensitivity and specificity of each assay. The test results yielded by these assays in a group of 165 fully characterized SLE patients were compared with the corresponding medical records.
  
  
  RESULTS
  The Anti-dsDNA-NcX ELISA was found to have a sensitivity of 60.9% and a specificity of 98.9% in all 964 individuals at the manufacturer's cutoff of 100 U/ml. At a comparable specificity of 99%, the sensitivity amounted to 59.9% for the Anti-dsDNA-NcX ELISA, 54.1% for the Farr assay, 53.6% for the antinucleosome ELISA and 35.8% for the anti-dsDNA ELISA. The CLIF assay had a sensitivity of 28.0% and a specificity of 98.2%. The Anti-dsDNA-NcX ELISA correlated mostly with global disease activity in a cross-sectional analysis. In a longitudinal analysis of 20 patients with 69 patient visits, changes in Anti-dsDNA-NcX ELISA and antinucleosome ELISA results correlated highly with changes in disease activity over time.
  
  
  CONCLUSIONS
  The use of dsDNA-complexed nucleosomes as antigens in ELISA leads to optimized determination of diagnosis and disease activity in SLE patients and is available for clinical practice.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, Berlin D-10117, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Biesen
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dähnrich
authors.forename: Anke
authors.initials: A
authors.lastname: Rosemann
authors.forename: Fidan
authors.initials: F
authors.lastname: Barkhudarova
authors.forename: Thomas
authors.initials: T
authors.lastname: Rose
authors.forename: Olga
authors.initials: O
authors.lastname: Jakob
authors.forename: Anne
authors.initials: A
authors.lastname: Bruns
authors.forename: Marina
authors.initials: M
authors.lastname: Backhaus
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.forename: Gerd-Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlumberger
authors.forename: Karl
authors.initials: K
authors.lastname: Egerer
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000276:immunology*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D009707:Nucleosomes; D004247:DNA