HLA genotyping in children with celiac disease allows to establish the risk of developing type 1 diabetes.

Abstract

Celiac Disease (CD) and Type 1 Diabetes (T1D) often co-occur and share genetic components in the HLA class II region. We aimed to study the usefulness of HLA genotyping in predicting the risk of developing T1D in patients with CD and the temporal relationship between these diseases. A cohort of 1,886 Sardinian patients, including 822 with CD, 1,064 with T1D, and 627 controls, underwent HLA class II typing. Seventy-six out of 822 CD patients were also affected by T1D (CD-T1D), and their HLA genotypes were analyzed for specific HLA associations with CD, T1D and controls. High-risk HLA-DQ genotypes, including HLA-DQ2.5/DQ8, -DQ2.5/DQ2.5, and -DQ2.5/DQ2.3, were strongly associated with CD-T1D with frequencies of 34.5%, 15.9%, and 18.8%, respectively. Conversely, certain HLA genotypes associated with CD appeared to confer protection against T1D development. Therefore, HLA genotyping allows the identification of those CD patients that might develop T1D. The frequency of patients with CD preceding T1D is higher in younger children than older ones, with implications for the early childhood approach to diabetes prevention. CD is a condition for future T1D development, and specific HLA genotypes can predict this risk. Early screening for celiac autoimmunity and subsequent HLA typing in CD children could help identify those at high risk for T1D, allowing for proactive interventions and immunotherapies to preserve beta-cell function. These findings may support the re-evaluation of HLA typing in children with CD.