title: Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?
abstract: OBJECTIVE
  The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients.
  
  
  METHODS
  In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes).
  
  
  RESULTS
  Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation.
  
  
  CONCLUSIONS
  We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, The Netherlands. h.g.otten@umcutrecht.nl.
authors.forename: Henny G
authors.initials: HG
authors.lastname: Otten
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Brummelhuis
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands; and Ludwig Boltzmann Institute of Osteology and AUVA Trauma Centre Meidling, Hanusch Hospital, and Sigmund Freud University, Vienna, Austria.
authors.forename: Ruth
authors.initials: R
authors.lastname: Fritsch-Stork
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Leavis
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Bram W
authors.initials: BW
authors.lastname: Wisse
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Ronald H W M
authors.initials: RHWM
authors.lastname: Derksen
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood*; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D003240:Connective Tissue Diseases / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D003362:Cost-Benefit Analysis; D017048:Health Care Costs; D006801:Humans; D011237:Predictive Value of Tests; D011933:Reagent Kits, Diagnostic / Q000191:economics; D015203:Reproducibility of Results; D012698:Serologic Tests / Q000191:economics
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; D011933:Reagent Kits, Diagnostic