Serological and Histological Concordance in the Diagnosis of Adult Coeliac Disease: A Review of Multicentre Evidence

Abstract

Coeliac disease in adults is diagnosed by agreement between a blood test and a duodenal biopsy, and the question of whether the biopsy can be omitted when the antibody titre is high enough has been settled in children and remains contested in adults. Both halves of the comparison turn out to be less firm than the phrase gold standard suggests. Objectives: To review the multicentre evidence on concordance between coeliac serology and duodenal histology in adults: how well a high antibody titre predicts villous atrophy, how that prediction depends on the population tested, how reproducibly the histology is graded, and what follows for the no-biopsy approach. Material and Methods: Narrative review of multicentre cohorts, systematic reviews and meta-analyses, interobserver agreement studies and society guidelines indexed in PubMed and the major gastroenterology journals. Studies were eligible if they reported the performance of serology against duodenal histology in a defined adult population, the reproducibility of histological grading, or guideline positions on diagnosis. No new patient data were generated; every accuracy estimate quoted is one published by the original investigators. Results: Pooling 18 studies covering 12,103 participants from 15 countries, IgA anti-tissue transglutaminase at or above ten times the upper limit of normal had a sensitivity of 51 per cent (95% CI 42-60) and a specificity of 100 per cent (95% CI 98-100), with a summary area under the curve of 0.83. Positive predictive value varied with the population tested, from 65 per cent where prevalence was 1 per cent to 99 per cent where it was 40 per cent. A three-cohort study reported sensitivity of 54.0 per cent, specificity of 90.0 per cent and positive predictive value of 98.7 per cent in a specialist clinic population. On the histological side, mean kappa between pathologist pairs was 0.35 for the Marsh-Oberhuber classification and 0.55 for a simplified three-tier system.
Conclusion: Discordance between serology and histology arises from both directions. A high titre is close to specific but misses around half of cases, so it can confirm but not exclude. Histology, the nominal reference standard, is graded with only fair agreement between pathologists at the mild end of the spectrum. The no-biopsy approach is defensible where pretest probability is high and indefensible as a population screening tool, and the difference is entirely a function of who is tested. Abbreviations: CD – Coeliac Disease, tTG – Tissue Transglutaminase, IgA-tTG – Immunoglobulin A Anti-Tissue Transglutaminase, EMA – Endomysial Antibody, DGP – Deamidated Gliadin Peptide, ULN – Upper Limit of Normal, IEL – Intraepithelial Lymphocyte, Vi:Cr – Villus Height to Crypt Depth Ratio, PPV – Positive Predictive Value, NPV – Negative Predictive Value, AUC – Area Under the Curve, HLA – Human Leukocyte Antigen.