Close-up view as gluten triggers celiac disease
MONASH U. (AUS) — A new study that visualizes an interaction between gluten and T-cells helps clarify what sets off celiac disease, which affects approximately one in 133 people.
An increasingly diagnosed chronic inflammatory disorder, celiac disease affects the digestive process of the small intestine.
When a person with celiac disease consumes gluten, their immune system triggers T-cells to fight the offending proteins, damaging the small intestine and inhibiting the absorption of important nutrients into the body. There are currently no treatments available apart from a diet completely free of gluten.
The researchers used the Australian Synchrotron to visually determine how T-cells of the immune system interact with gluten, a protein found in wheat, rye, and barley, which causes celiac disease.
The discovery, reported in the journal Immunity, will boost attempts to produce a treatment allowing sufferers to resume a normal diet.
About half the population is genetically susceptible to celiac disease because they carry the immune response genes HLA-DQ2 or HLA-DQ8. At least one in 20 people who carry HLA-DQ2 and about one in 150 who have HLA-DQ8 develop celiac disease, but people with other versions of the HLA-DQ genes are protected.
This has led researchers to question how the immune system senses gluten.
Hugh Reid, a senior research fellow at Monash University, says the discovery is an important breakthrough for celiac disease and autoimmune disease.
“This is the first time that the intricacies of the interaction between gluten and two proteins that initiate immune responses have been visualized at a sub-molecular level,” says Reid, who led the study with Professor Jamie Rossjohn, also of Monash University.
This insight into a central event in celiac disease will assist ImmusanT to develop a blood test and a therapeutic vaccine, Nexvax2, for patients with celiac disease who carry the gene HLA-DQ2. It is intended to restore immune tolerance to gluten and allow patients to again include gluten in their diet.
Future studies will investigate whether T-cell activation by gluten in patients with HLA-DQ2 follows similar principles as observed in this study that focused on HLA-DQ8-mediated celiac disease.
Chief Scientific Officer at ImmusanT and co-author of the study Bob Anderson says the research presented a unique opportunity.
“Because we now know the gluten peptides responsible for celiac disease, we can interrogate the molecular events leading to a self-destructive immune response,” says Anderson.
Investigators from the Leiden University, University of Melbourne, and Cardiff University are also co-authors of the study, which was supported by an Australian Research Council Linkage grant.
Source: Monash University
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