title: Optimization and diagnostic performance of a single multiparameter lineblot in the serological workup of systemic sclerosis.
abstract: BACKGROUND
  Detection of systemic sclerosis-associated antibodies (SSc-Ab) in routine clinical practice is mostly restricted to anti-centromere and anti-topoisomerase-I antibodies. However, also other SSc-Ab (e.g. anti-RNA-polymerase-III, anti-PM/Scl, anti-fibrillarin and anti-Th/To) have been shown to be valuable diagnostic and prognostic markers for the disease, but testing methodologies for their detection are laborious and time-consuming. This study aimed to optimize interpretational criteria of a multiparameter lineblot (LB) for the parallel detection of SSc-Ab. We also assessed its global diagnostic value as an alternative for combined conventional techniques (CCT) in the serological workup of systemic sclerosis (SSc) patients.
  
  
  METHODS
  The presence of SSc-Ab (anti-centromere, anti-topoisomerase-I, anti-RNA-polymerase-III, anti-PM/Scl, anti-fibrillarin and anti-Th/To) was identified by LB on 145 consecutive SSc patients and on 277 disease controls. Diagnostic sensitivity and specificity were calculated for both individual reactivities and the global LB. Cohen's kappa coefficient was used to examine agreement between LB and CCT and guided the definition of final interpretational criteria for LB.
  
  
  RESULTS
  Applying the optimal cut-off values and interpretational criteria, LB identified SSc-Ab in 110 SSc patients (sensitivity=76%) and in 19 disease controls (specificity=93%). Globally, there was a substantial agreement between CCT and LB (κ=0.787, concordance 92.4%). LB and CCT showed a very good correlation (κ>0.800) for most SSc-Ab (anti-centromere, anti-topoisomerase-I, anti-RNA-polymerase-III and anti-PM/Scl). The best agreement for anti-RNA-polymerase-III and anti-PM/Scl was achieved when positivity for both components was taken as a criterion.
  
  
  CONCLUSIONS
  LB is a reliable alternative for the laborious and time-consuming conventional techniques in the diagnostic workup of SSc, especially for the detection of anti-centromere, anti-topoisomerase-I, anti-RNA-polymerase-III and anti-PM/Scl.
authors.affiliation: Laboratory of Clinical Biology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital (2P8), De Pintelaan 185, B-9000 Ghent, Belgium. carolien.bonroy@uzgent.be
authors.forename: C
authors.initials: C
authors.lastname: Bonroy
authors.forename: J
authors.initials: J
authors.lastname: Van Praet
authors.forename: V
authors.initials: V
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Van Steendam
authors.forename: T
authors.initials: T
authors.lastname: Mimori
authors.forename: E
authors.initials: E
authors.lastname: Deschepper
authors.forename: D
authors.initials: D
authors.lastname: Deforce
authors.forename: K
authors.initials: K
authors.lastname: Devreese
authors.forename: F
authors.initials: F
authors.lastname: De Keyser
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D002503:Centromere / Q000276:immunology; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D005260:Female; D006801:Humans; D007158:Immunologic Techniques / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012320:RNA Polymerase III / Q000276:immunology; D012595:Scleroderma, Systemic / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002868:Chromosomal Proteins, Non-Histone; C047458:fibrillarin; D012320:RNA Polymerase III; D004264:DNA Topoisomerases, Type I