title: Immunoassays for the detection of IgA antibodies to tissue transglutaminase: significance of multiples of the upper limit of normal and inter-assay correlations.
abstract: BACKGROUND
  The presence of IgA antibodies to tissue transglutaminase (anti-tTg) is associated with variable risk for celiac disease. The use of common multiples of the upper limit of normal (ULN) has been suggested to optimize diagnostic pathways as well as improve harmonization between assays.
  
  
  METHODS
  The characteristics of four anti-tTG IgA assays relative to endomysial IgA (EMA) by indirect immunofluorescence assay (IFA) as reference test were assessed. Commutability between anti-tTG immunoassays and/or EMA based on manufacturer's recommended cut-off values and three common multiples of ULN (3×, 5× and 10×) was also investigated. Sera from 200 patients and 100 healthy individuals were analyzed.
  
  
  RESULTS
  At manufacturer's cut-off; the sensitivities for the tTG assays ranged from 72.5% to 98.6% and specificities from 60.3% to 99.2%. The percent positive agreements between any anti-tTG and EMA or any two anti-tTG immunoassays varied from 56.7% to 98.0% and 46.7% to 100.0%, respectively. At 3×, 5× or 10× ULNs, the inter-rater reliability as measured by Cohen κ between any two anti-tTG assays were quite variable and ranged from 0.28 to 0.96, 0.26 to 0.89 or 0.13 to 0.78, respectively. Furthermore, the percent positive agreements between any two anti-tTg IgA immunoassays ranged from 83.1% to 98.2%, 92.0% to 100%, or 100%, at 3×, 5× or 10×, respectively.
  
  
  CONCLUSIONS
  Commutability between tTG IgA immunoassays or tTG IgA and EMA is kit-dependent and common multiples of the ULN are not sufficient to correct for inter-assay variations. Many factors influence the performance of anti-tTG IgA assays which limit their commutability.
authors.forename: Brenda B
authors.initials: BB
authors.lastname: Suh-Lailam
authors.forename: K Wayne
authors.initials: KW
authors.lastname: Davis
authors.forename: Anne E
authors.initials: AE
authors.lastname: Tebo
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001323:Autoantibodies / Q000097:blood; D002446:Celiac Disease / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D019204:GTP-Binding Proteins / Q000276:immunology*; D006801:Humans; D007118:Immunoassay; D007070:Immunoglobulin A / Q000097:blood*; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012372:ROC Curve; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D011503:Transglutaminases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D011933:Reagent Kits, Diagnostic; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins