title: Clinical and serological associations of autoantibodies to the Ku70/Ku80 heterodimer determined by a novel chemiluminescent immunoassay.
abstract: BACKGROUND
  Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of anti-Ku antibodies in different medical conditions using a novel chemiluminescent immunoassay.
  
  
  METHODS
  Serum samples from adult patients with systemic lupus erythematosus (SLE, n=305), systemic sclerosis (SSc, n=70) and autoimmune myositis patients (AIM, n=109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n=30; infectious diseases, n=17) and healthy individuals (n=167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n=1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLE patient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review.
  
  
  RESULTS
  In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious disease patients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs.
  
  
  METHODS
  In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA.
  
  
  CONCLUSIONS
  Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc.
authors.affiliation: Inova Diagnostics Inc., San Diego, USA mmahler@inovadx.com m.mahler.job@web.de.
authors.forename: M
authors.initials: M
authors.lastname: Mahler
authors.affiliation: Neuss Clinic for Rheumatology Dr Gürtler, Neuss, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Swart
authors.affiliation: Inova Diagnostics Inc., San Diego, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Wroclaw Medical University, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Szmyrka-Kaczmarek
authors.affiliation: Department of Medicine, Division of Rheumatology, and Laboratory for Research in Autoimmunity, Research Centre of the Centre Hospitalier de l'Université de Montréal, University of Montreal Faculty of Medicine, Montreal, Canada.
authors.forename: J-L
authors.initials: JL
authors.lastname: Senécal
authors.affiliation: Hôpital du Sacré-Coeur, University of Montreal, Montreal, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Troyanov
authors.affiliation: Faculty of Medicine, Dalhousie University and Nova Scotia Health Authority Halifax, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Hanly
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fritzler
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D016000:Cluster Analysis; D006801:Humans; D000072200:Ku Autoantigen / Q000276:immunology*; D008163:Luminescent Measurements / Q000379:methods*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D009220:Myositis / Q000276:immunology*; D012372:ROC Curve; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000072200:Ku Autoantigen
keywords: Ku; SLE; autoantibodies; autoimmune myositis; systemic lupus erythematosus