The molecular basis for the efficacy of ZED1227 — a transglutaminase 2 inhibitor — in celiac disease is unknown. We show that orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation at the transcriptome level, and that individuals with high-risk HLA class II celiac disease consistently display a more ‘deteriorated’ molecular phenotype.
This is a preview of subscription content, log in via an institution to check access.
References
Besser, H. A. & Khosla, C. Celiac disease: mechanisms and emerging therapeutics. Trends Pharmacol. Sci. 44, 949–962 (2023). A review article that presents current understanding of CeD pathogenesis and how this knowledge is being harnessed for therapeutic design and development.
Dotsenko, V. & Viiri, K. Genome-wide transcriptomic analysis of intestinal mucosa in celiac disease patients on a gluten-free diet and post gluten challenge. Cell Mol. Gastroenterol. Hepatol. 11, 13–32 (2021). This paper reports gluten challenge-induced duodenal biopsy transcriptomic changes and created a molecular morphometric tool to measure mucosal injury objectively.
Schuppan, D. & Mäki, M. A randomized trial of a transglutaminase 2 inhibitor for celiac disease. N. Engl. J. Med. 385, 35–45 (2021). This paper reports a proof-of-concept trial that treatment with ZED1227 attenuates gluten-induced mucosal damage in patients with CeD.
Sollid, L. M. & Jabri, B. Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat. Rev. Immunol. 13, 294–302 (2013). A review article that presents CeD as a model for autoimmunity in general.
Christophersen, A. & Davis, M. M. Distinct phenotype of CD4+ cells driving celiac disease identified in multiple autoimmune conditions. Nat. Med. 25, 734–737 (2019). This paper reports a way to identify CD4+ T cells specific for environmental disease-driving antigens in autoimmune conditions.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Dotsenko, V. et al. Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease. Nat. Immmunol. https://doi.org/10.1038/s41590-024-01867-0 (2024).
Rights and permissions
About this article
Cite this article
Transcriptomic analysis of celiac disease treatment with transglutaminase 2 inhibitor. Nat Immunol 25, 1140–1141 (2024). https://doi.org/10.1038/s41590-024-01870-5
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41590-024-01870-5
- Springer Nature America, Inc.