title: Troponin-specific autoantibody interference in different cardiac troponin I assay configurations.
abstract: BACKGROUND
  Autoantibodies to cardiac troponins (cTnAAb) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays. The aim of this study was to explore the degree of cTnAAb interference in different cTnI assay configurations.
  
  
  METHODS
  Ternary troponin complex was added into samples (serum or plasma, n = 132, 68% cTnAAb positive) from individuals without known cardiac conditions. The recovery of cTnI was then measured with 6 investigational cTnI assays (2, 3, or 4 antibodies per assay). Three of these assays were then selected for further comparison by use of samples (plasma, n = 210, 33% cTnAAb positive) from non-ST-elevation acute coronary syndrome patients in the FRISC-II (FRagmin/Fast Revascularisation during InStability in Coronary artery disease) cohort. Finally, these results were compared to those obtained with 3 commercial cTnI assays.
  
  
  RESULTS
  Analytical recoveries varied widely among the 6 investigational assays. Notably the low recoveries (median 9%) of the midfragment-targeting reference assay were normalized (median 103%) with the use of the 4-antibody assay construct (3 capture, 1 tracer antibody) with only 1 antibody against a midfragment epitope. Reduced analytical recoveries correlated closely with measured autoantibody amounts. cTnI concentrations from cTnAAb-positive patient samples determined with 3 investigational assays confirmed the reduced concentrations expected from the low analytical recoveries. The results from the commercial cTnI assays with antibody selections representative for contemporary assay constructs revealed a similar underestimation (up to 20-fold) of cTnI in cTnAAb-positive samples.
  
  
  CONCLUSIONS
  A novel cTnI assay deviating from the conventional IFCC-recommended midfragment approach substantially improves cTnI detection in samples containing cTnAAbs.
authors.affiliation: Department of Biotechnology, University of Turku, Turku, Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Savukoski
authors.forename: Emilia
authors.initials: E
authors.lastname: Engström
authors.forename: Janne
authors.initials: J
authors.lastname: Engblom
authors.forename: Noora
authors.initials: N
authors.lastname: Ristiniemi
authors.forename: Saara
authors.initials: S
authors.lastname: Wittfooth
authors.forename: Bertil
authors.initials: B
authors.lastname: Lindahl
authors.forename: Kai M
authors.initials: KM
authors.lastname: Eggers
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D000939:Epitopes; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D007118:Immunoassay; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D019210:Troponin I