title: Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease.
abstract: BACKGROUND
  The European Society for Pediatric Gastroenterology and Nutrition states that if IgA anti-tissue transglutaminase (tTG) exceeds 10 times the upper limit of normal (ULN), there is the possibility to diagnose celiac disease (CD) without duodenal biopsy, if supported by anti-endomysium testing and human leukocyte antigen (HLA) typing. We aimed to evaluate whether combining IgA tTG and IgG anti-deamidated gliadin peptide (DGP) antibody testing and taking into account the antibody levels improves clinical interpretation.
  
  
  METHODS
  We calculated likelihood ratios for various test result combinations using data obtained from newly diagnosed CD patients (n=156) [13 children <2 years, 45 children between 2 and 16 years, and 98 adults (>16 years)] and 974 disease controls. All patients and controls underwent duodenal biopsy. IgA anti-tTG and IgG anti-DGP assays were from Thermo Fisher and Inova.
  
  
  RESULTS
  Likelihood ratios for CD markedly increased with double positivity and increasing antibody levels of IgA anti-tTG and IgG anti-DGP. Patients with double positivity and high antibody levels (>3 times, >10 times ULN) had a high probability for having CD (likelihood ratio ≥649 for >3 times ULN and ∞ for >10 times ULN). The fraction of CD patients with double positivity and high antibody levels was 59%-67% (depending on the assay) for >3 ULN and 33%-36% (depending on the assay) for >10 ULN, respectively. This fraction was significantly higher in children with CD than in adults.
  
  
  CONCLUSIONS
  Combining IgG anti-DGP with IgA anti-tTG and defining thresholds for antibody levels improves the serologic diagnosis of CD.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Oyaert
authors.forename: Pieter
authors.initials: P
authors.lastname: Vermeersch
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.forename: Martin
authors.initials: M
authors.lastname: Hiele
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vandeputte
authors.forename: Ilse
authors.initials: I
authors.lastname: Hoffman
authors.forename: Xavier
authors.initials: X
authors.lastname: Bossuyt
mesh_terms: D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D016022:Case-Control Studies; D002446:Celiac Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D008297:Male; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012680:Sensitivity and Specificity; D011503:Transglutaminases / Q000276:immunology*; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C049937:anti-IgA; C048844:anti-IgG; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins