title: Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases.
abstract: OBJECTIVE
  Antinuclear antibodies (ANA) are a serological hallmark of systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). While a number of ANA patterns detected by indirect immunofluorescence (IIF) have diagnostic significance, autoantibodies producing the dense fine speckled (DFS) pattern have been reported to be more prevalent in healthy individuals than in SARD.
  
  
  METHODS
  Sequential samples submitted for ANA testing were screened for anti-DFS antibodies by IIF (n = 3263). Samples with the DFS pattern were tested for anti-DFS70/lens epithelium-derived growth factor (LEDGF) antibodies by ELISA and by a novel chemiluminescence assay (CIA, Quanta Flash DFS70). Sera from patients with various diseases and healthy individuals were tested for anti-DFS70/LEDGF antibodies by CIA. A cohort of 251 patients with SLE was used to analyze serological and clinical associations of anti-DFS70 antibodies.
  
  
  RESULTS
  The frequency of anti-DFS antibodies by IIF was 1.62%. The prevalence of anti-DFS70/LEDGF antibodies as detected by CIA in the different cohorts was 8.9% in healthy individuals, 2.8% in SLE, 2.6% in rheumatoid arthritis, 4.0% in asthma, 5.0% in interstitial cystitis, 1.7% in Graves' disease, and 6.0% in Hashimoto's thyroiditis. Of note, the prevalence of anti-DFS70/LEDGF antibodies was significantly higher in healthy individuals compared to patients with SARD (p = 0.00085). In SLE results, anti-DFS70/LEDGF antibodies were not significantly associated with clinical features or other autoantibodies typically found in SLE. Only 1/7 SLE sera showed anti-DFS70/LEDGF, but no other autoantibody reactivity.
  
  
  CONCLUSIONS
  "Monospecific" anti-DFS70/LEDGF antibodies may represent a biomarker for differentiating SARD from non-SARD individuals, but there is a need for a reliable assay to ensure reactivity to DFS70.
authors.affiliation: Department of Research, Inova Diagnostics Inc., San Diego, California, USA. mmahler@inovadx.com
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
authors.forename: Todd
authors.initials: T
authors.lastname: Parker
authors.forename: Carol L
authors.initials: CL
authors.lastname: Peebles
authors.forename: Luis E
authors.initials: LE
authors.lastname: Andrade
authors.forename: Andreas
authors.initials: A
authors.lastname: Swart
authors.forename: Yvette
authors.initials: Y
authors.lastname: Carbone
authors.forename: David J
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: Danilo
authors.initials: D
authors.lastname: Villalta
authors.forename: Nicola
authors.initials: N
authors.lastname: Bizzaro
authors.forename: John G
authors.initials: JG
authors.lastname: Hanly
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D050031:Hashimoto Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012216:Rheumatic Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000888:Antibodies, Anti-Idiotypic; D015415:Biomarkers; C504649:PSIP1 protein, human; D014157:Transcription Factors