Pre-symptomatic diagnosis of Celiac Disease in predisposed children: the role of gene expression profile

Background and objectives: The prevalence of Celiac Disease (CD) has increased significantly in recent years, and risk prediction and early diagnosis has become imperative especially in at risk families. In a previous study, we identified individuals with CD based on the expression profile of a set of candidate genes in peripheral blood monocytes. Here we evaluated the expression of a panel of CD candidate genes in peripheral blood mononuclear cells (PBMCs) from at risk infants long time before any symptom or production of antibodies. Methods: We analysed the gene expression of a set of 9 candidate genes, associated with CD, in22HLA predisposed children from at risk families for CD, followed from birth to 6 years of age. Nine of them developed CD (cases)and 13 did not (controls). We analysed gene expression at three different time points (age matched in the two groups): 4-19 months before diagnosis, at the time of CD diagnosis, and after at least one year of a gluten-free diet. At similar age points controls were also evaluated. Results: Three genes (KIAA, TAGAP and SH2B3) were overexpressed in cases, compared to controls, at least 9 months before CD diagnosis. At a stepwise discriminant analysis,4 genes (RGS1, TAGAP, TNFSF14 and SH2B3) differentiate cases from controls before serum antibodies production and clinical symptoms. Multivariate equation correctly classified CD from non-CD children in 95.5% of cases. Conclusions: The expression of a small set of candidate genes in PBMCs can predict celiac disease at least 9 months before the appearance of any clinical and serological signs of the disease.