A Systems Biology Approach to the Pathogenesis of Celiac Disease: Identification of Potential Protective and Promoting Mechanisms Publisher



M Fadaie MAHMOOD ; A Khalafiyan ANIS ; E Ghafouri ELHAM ; T Ranjbarnejad TAYEBEH ; S Moein SHIVA
Source: Advanced Biomedical Research Published:2024

Abstract

Background: Celiac disease (CeD) is an autoimmune enteropathy triggered by dietary gluten. Almost 90% of CeD patients have HLA-DQ2 or -DQ8 haplotypes. As a high proportion of first-degree relatives (FDRs) of CeD patients have the same haplotype, it is assumed that they are at a higher risk of disease development than the general population. Nevertheless, the prevalence of CeD among FDRs is considerably low (7.5%). Materials and Methods: In order to figure out this discrepancy, a microarray dataset of intestinal mucosal biopsies of CeD patients, FDRs, and control groups was reanalyzed, and a protein-protein interaction network was constructed. Results: Principal component analysis showed that CeD and FDR groups are far away in terms of gene expression. Comparing differentially expressed genes of both networks demonstrated inverse expression of some genes mainly related to cell cycle mechanisms. Moreover, analysis of the modular structures of up- and downregulated gene networks determined activation of protein degradation mechanisms and inhibition of ribosome-related protein synthesis in celiac patients with an upside-down pattern in FDRs. Conclusions: The top-down systems biology approach determined some regulatory pathways with inverse function in CeD and FDR groups. These genes and molecular mechanisms could be a matter of investigation as potential druggable targets or prognostic markers in CeD. © 2025 Elsevier B.V., All rights reserved.