Visual Universitätsmedizin Mainz

Celiac disease, Wheat sensitivity

The molecular pathogenesis and immunology of chronic intestinal diseases, including celiac disease.

Prior and current research has lead to the identification of the celiac disease autoantigen, tissue transglutaminase (TG2), and focused on exploring the role of TG2 in celiac disease pathogenesis, including the clinical development of a TG2 inhibitor as novel treatment for celiac disease within the CI3 excellence cluster. Several approaches are undertaken to develop a mouse model for celiac disease, including mice with a humanized immune system, to allow the preclinical testing of non-dietary and immune modulatory therapies. We have recently identified amylase trypsin inhibitors (ATIs) of wheat/barley/rye as triggers of nonceliac/non-allergy wheat sensitivity that after oral ingestion uniquely activate intestinal myeloid cells via toll like receptor 4 to cause low level intestinal immune stimulation. How far nutritional ATIs promote intestinal and extraintestinal inflammatory diseases is subject of numerous current preclinical and imminent clinical studies. We also search for serum activity markers of celiac disease and wheat sensitivity. A growing group in the lab studies the myeloid cells and their modulation in inflammatory bowel diseases, including the search for novel biomarkers of disease activity.

 

Milestone achievements in celiac disease and wheat sensitivity

1.   Identification tissue transglutaminase as the autoantigen of celiac disease
Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D.
Identification of tissue transglutaminase as the autoantigen of celiac disease.
Nat Med 1997;3:797-801.

2.   Establishment of the celiac disease blood test for antibodies to tissue transglutaminase
Dieterich W, Laag E, Schöpper H, Volta U, Ferguson A, Gillett H, Riecken EO,
Schuppan D. Autoantibodies to tissue transglutaminase as predictors of celiac
disease. Gastroenterology 1998;115:1317-21.

3.   Identification of the wheat amylase trypsin inhibitors as nutritional triggers of non-celiac/non-allergy wheat sensitivity
Junker Y, Zeissig S, Kim SJ, Barisani D, Wieser H, Leffler DA, Zevallos V, Libermann TA, Dillon S, Freitag TL, Kelly CP, Schuppan D. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med 2012;209:2395-408.

4.   Development of an endoscopic method to clearly identify patients with wheat and other food allergies that cannot be identified by other means
Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Röcken C, Brasch J, Bethge J, Böttner M, Klose J, Milla PJ. Confocal endomicroscopy reveals food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 2014;147:1012-20.

 

Key references:

Fritscher-Ravens et al, Gastroenterology 2014.pdf (Pdf-file, 1,8 MB)

Leffler et al, Gut 2013.pdf (Pdf-file, 377,2 KB)

Junker et al, J Exp Med 2012.pdf (Pdf-file, 2,3 MB)

Leffler, Schuppan, Am J Gastroenterol 2010.pdf (Pdf-file, 151,7 KB)

Schuppan et al, Gastroenterology 2009.pdf (Pdf-file, 914,3 KB)

Dieterich et al, Gatroenterology 1998.pdf (Pdf-file, 95,3 KB)

Dieterich et al, Nat Med 1997.pdf (Pdf-file, 640,7 KB)