Antibodies Are Predictive for Diagnosis of Celiac Disease in Pediatric Type 1 Diabetes

Background: Children and adolescents with type 1 diabetes (T1D) have a higher risk of developing celiac disease (CD) than the general population. However, the main screening antibody, IgA anti-transglutaminase 2 (TGA-IgA), can fluctuate in T1D and there is no threshold for performing diagnostic biopsies.

Objectives: The study aims to define an optimal TGA-IgA cut-off for performing diagnostic biopsies for CD confirmation and to assess whether tracking TGA-IgA evolution or adding other antibodies can improve biopsy indications.

Methods: Retrospective longitudinal analysis of pediatric T1D individuals diagnosed at two centers in Switzerland between 2000 and 2021, from T1D diagnosis to CD diagnosis or the age of 18 years.

Results: We included 588 individuals with T1D, compromising 2944 TGA-IgA values. 34 (5.8%) developed CD during follow-up, of whom 50% had CD- associated symptoms at CD diagnosis. Balancing sensitivity and specificity TGA-IgA around 6.1xULN was the best cut-off for performing diagnostic biopsies. The inclusion of IgG antibodies against deamidated gliadin peptides (GLA-IgG) achieved a higher AUC of 0.79 (95% CI 0.6-1) with 80% accuracy compared to each antibody alone. CD diagnosis within two years of T1D, representing two-thirds of CD, was marked by elevated TGA-IgA at T1D diagnosis. Later CD diagnosis was associated with a more gradual increase of TGA-IgA.

Conclusion: Our results suggest an indication for biopsy for CD confirmation at a TGA-IgA cut-off around 6.1xULN. Including GLA-IgG can potentially increase precision. TGA-IgA determination at T1D diagnosis may help to identify individuals at risk of CD early on.