Therapeutic TG2 Inhibition Reverses Systemic Multiomic Dysregulation in Celiac Disease

ABSTRACT: Background and Aims: Celiac disease (CeD) is an autoimmune disease triggered by dietary gluten in genetically predisposed individuals. Deamidation of gluten peptides by the CeD autoantigen and enzyme transglutaminase 2 (TG2) is central to the pathogenesis of CeD. Inhibition of TG2 with the specific inhibitor ZED1227 effectively prevents gluten-induced histological damage in CeD patients. Here we aimed to explore the blood DNA methylomic changes in ZED1227-treated CeD patients undergoing a gluten challenge. Results: Drug treatment revealed consistent patterns suggesting normalization of the DNA methylome indicating that ZED1227 attenuated the systemic responses to gluten challenge. Conclusions: These findings provide evidence that ZED1227 can significantly prevent the gluten-induced CeD-associated systemic changes. Clinical trial: EudraCT 2017-002241-30

ORGANISM(S): Homo sapiens

PROVIDER: GSE319777 | GEO | 2026/06/18

REPOSITORIES: GEO