Serological screening for coeliac disease in an adult general population: the HUNT study

Gut. 2025 May 7;74(6):918-925. doi: 10.1136/gutjnl-2024-333886.

Abstract

Background: A large proportion of individuals with coeliac disease (CeD) remain undiagnosed.

Objective: The aim of this study was to assess serological screening for CeD in the adult general population.

Design: The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017-2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found.

Results: Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10× ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals.

Conclusion: The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD.

Keywords: COELIAC DISEASE; SCREENING; SMALL INTESTINAL BIOPSY.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Biopsy
  • Celiac Disease* / blood
  • Celiac Disease* / diagnosis
  • Celiac Disease* / epidemiology
  • Celiac Disease* / pathology
  • Duodenum / pathology
  • Female
  • GTP-Binding Proteins / immunology
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Male
  • Mass Screening* / methods
  • Middle Aged
  • Norway / epidemiology
  • Predictive Value of Tests
  • Protein Glutamine gamma Glutamyltransferase 2
  • Serologic Tests
  • Transglutaminases / immunology
  • Young Adult

Substances

  • Immunoglobulin A
  • Immunoglobulin G
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • Autoantibodies
  • GTP-Binding Proteins