Exploring the gut-thyroid axis in paediatric coeliac disease patients of Hellenic origin - A novel immunogenetics strategy

Objectives and study: Differential diagnosis and theranostics of a series of autoimmune inflammatory disorders remain challenging as we still need to dissect the molecular determinants and cross-talk in the cell signaling of the gutthyroid axis. Several genetic, epidemiological, clinical, serological, and pathophysiological data indicate that coeliac disease is associated with autoimmune thyroid disorders and in particular, Graves’ disease. Today, no clear nomogram is effective to allow for optimum disease management and patient stratification. Herein, we explore the role of selected genomic variants for overlapping susceptibility between Graves’ disease and paediatric coeliac disease aiming for an immunogenetic model towards the identification of coeliac disease patients with an increased risk of developing Graves’ disease. Methods: Extensive data mining, pathway analysis and literature review resulted in the selection of CTLA4, BACH2 and IL23R variants. For data validation, coeliac paediatric patients of Hellenic origin (n=109) and their ethnically matched counterparts (n=111) were genotyped by PCR and Sanger sequencing. Hardy- Weinberg equilibrium was determined by Pearson’s goodness-of-fit chi-square, loglikelihood ratio chi-square and Exact tests. Genotype and allele frequencies were evaluated by the Fisher’s Exact test. A two-tailed p-value of <0.05 was considered statistically significant. The R project for statistical computing (R i386 3.2.1) was used. Results: Selected CTLA4, BACH2 and IL23R variants may account for the overlapping susceptibility between Graves’ disease and paediatric coeliac disease in patients of Hellenic origin. Conclusion: CTLA4, BACH2 and IL23R variants may serve as the building block of a nomogram to optimize Graves’ and Coeliac disease management and patient stratification.