Abstract
Celiac disease (CD) diagnosis in children with sub-threshold tissue transglutaminase autoantibody (anti-TG2) levels requires a small intestinal biopsy. Through RNA sequencing and real-time PCR of small intestinal biopsies, gene expression in such children was compared with the expression in children with active CD and anti-TG2 levels above the threshold, and with non-CD children. The study also included CD children with a non-diagnostic first biopsy to explore early gene expression changes in CD. The aim of the study was to explore gene expression in relation to anti-TG2 levels, investigate gene expression in Potential CD, and provide a gene expression profile to aid in CD diagnostics. The results showed that in active CD, expression changes involved genes associated with e.g., immune response, transport, angiogenesis, and epithelial barrier function, with even more pronounced changes of genes associated with cell cycle progression, absorption, lipid and lipoprotein processes, and retinoid metabolism in the active CD group with higher anti-TG2 levels. Gene expression changes in CD children with a non-diagnostic first biopsy showed large inter-individual variations, but in general, gene expressions were associated with many of the same biological contexts as in active CD, including epithelial barrier function. Overall, the results show that gene expression profiling has great potential as a complement to the histopathologic assessment in CD diagnostics, even early in the disease course, but probably cannot be used for prognostic purposes.