Diagnostic Accuracy of IgA Anti-transglutaminase Antibodies Measured by CLIA for Predicting Villous Atrophy in Coeliac Disease

Hospital Mutua de Terrassa

Status: Completed

Conditions: Coeliac Disease

Study type: Observational

Funder types: Other

Identifiers

NCT07364461

P/23-168

Details and patient eligibility

About

Celiac disease (CD) is an autoimmune disorder in which ingestion of gluten leads to immune-mediated damage of the small intestine. Diagnosis has traditionally required histological confirmation of duodenal villous atrophy.

Since 2012, European guidelines have allowed a biopsy-free diagnosis in paediatric patients with IgA anti-tissue transglutaminase 2 antibodies (TGA) levels greater than 10 times the upper limit of normal (>10 × ULN). In 2025, the diagnostic guidelines for adult CD included the possibility of biopsy-free diagnosis in patients younger than 45 years presenting TGA >10 × ULN, confirmed in a second serum sample. In both paediatric and adult guidelines, the supporting evidence was based almost exclusively on enzyme immunoassays (EIA) using chromogenic substrates such as ELISA or fluorogenic substrates such as FEIA.

In recent years, chemiluminescence immunoassays (CLIA) have largely replaced EIA in routine clinical practice. However, the optimal threshold for CD screening and for biopsy-free diagnosis using CLIA remains unclear, and the few available studies suggest values substantially higher than those established for EIA. Differences in analytical performance, wide variability in cut-off values, potential sex differences and limited real-world data raise concerns about the direct application of the >10 × ULN criterion to CLIA assays.

The primary aim of this study is to evaluate, in a community setting, the performance of CLIA-based TGA measurement to establish a threshold with high specificity and positive predictive value for duodenal villous atrophy (Marsh 2-3) suitable for biopsy-free CD diagnosis and to evaluate potential age and sex-related differences. The secondary aims are: 1) to determine the optimal cut-off for CD with duodenal atrophy screening; 2) to assess the accuracy of the manufacturer recommended cut-off.

Enrollment: 765 patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Having undergone duodenal biopsy and a complete CD diagnostic work-up
• Eating a gluten-containing diet

Exclusion criteria

• Having an unsuitable or non-performed duodenal biopsy
• Incomplete clinical data
• Inconclusive diagnostic findings
• Previous diagnosis of CD with duodenal biopsy performed during gluten-free diet (GFD)
• IgA deficiency

Trial design

765 participants in 2 patient groups

CD patients

Control