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

Abstract

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 cutoff 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 2 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, comprising 2944 TGA-IgA values. Thirty-four (5.8%) developed CD during follow-up, of whom 50% had CD-associated symptoms at CD diagnosis. Balancing sensitivity and specificity TGA-IgA around 6.1 × upper limit of normal was the best cutoff for performing diagnostic biopsies. The inclusion of IgG antibodies against deamidated gliadin peptides achieved a higher area under the curve of 0.79 (95% CI, 0.6-1) with 80% accuracy compared to each antibody alone. CD diagnosis within 2 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 cutoff around 6.1 × upper limit of normal. Including IgG antibodies against deamidated gliadin peptides can potentially increase precision. TGA-IgA determination at T1D diagnosis may help to identify individuals at risk of CD early on.

Keywords: IgA anti-transglutaminase 2 antibody; IgG anti-deamidated gliadin peptides antibody; screening strategy; serology.