Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment.
| Autor: | Verdu EF; Division of Gastroenterology, Department of Internal Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada., Schuppan D; Institute of Translational Immunology,Research Center for Immune Therapy and Celiac Center, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: detlef.schuppan@unimedizin-mainz.de. |
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| Jazyk: | angličtina |
| Zdroj: | Gastroenterology [Gastroenterology] 2021 Nov; Vol. 161 (5), pp. 1395-1411.e4. Date of Electronic Publication: 2021 Aug 17. |
| DOI: | 10.1053/j.gastro.2021.08.016 |
| Abstrakt: | Celiac disease (CeD) is a frequent immune-mediated disease that affects not only the small intestine but also many extraintestinal sites. The role of gluten proteins as dietary triggers, HLA-DQ2 or -DQ8 as major necessary genetic predisposition, and tissue transglutaminase (TG2) as mechanistically involved autoantigen, are unique features of CeD. Recent research implicates many cofactors working in synergism with these key triggers, including the intestinal microbiota and their metabolites, nongluten dietary triggers, intestinal barrier defects, novel immune cell phenotypes, and mediators and cytokines. In addition, apart from HLA-DQ2 and -DQ8, multiple and complex predisposing genetic factors and interactions have been defined, most of which overlap with predispositions in other, usually autoimmune, diseases that are linked to CeD. The resultant better understanding of CeD pathogenesis, and its manifold manifestations has already paved the way for novel therapeutic approaches beyond the lifelong strict gluten-free diet, which poses a burden to patients and often does not lead to complete mucosal healing. Thus, supported by improved mouse models for CeD and in vitro organoid cultures, several targeted therapies are in phase 2-3 clinical studies, such as highly effective gluten-degrading oral enzymes, inhibition of TG2, cytokine therapies, induction of tolerance to gluten ingestion, along with adjunctive and preventive approaches using beneficial probiotics and micronutrients. These developments are supported by novel noninvasive markers of CeD severity and activity that may be used as companion diagnostics, allow easy-to perform and reliable monitoring of patients, and finally support personalized therapy for CeD. (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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