An increasingly diagnosed chronic inflammatory disorder, celiac disease affects the digestive process of the small intestine. When a person with celiac disease consumes gluten, a protein found in wheat, rye and barley, their immune system triggers T-cells to fight the offending proteins, which damages the small intestine and inhibits absorption of important nutrients into the body. There are no treatments, apart from making sure to eat no foods with gluten.
About half the population is genetically susceptible to celiac disease because they carry the immune response genes HLA-DQ2 or HLA-DQ8. One in 20 people who carry HLA-DQ2 and about one in 150 who have HLA-DQ8 may develop celiac disease, but people with other versions of the HLA-DQ genes will not.
The researchers used the Australian Synchrotron to visually determine how T-cells of the immune system interact with gluten. Unlike an accelerator such as the LHC, the Australian Synchroton is a light source rather than a collider, making it ideal for the new study. The end goal of the project is to produce a treatment which allows celiac sufferers to resume a normal diet.
Knowing which genes were likely to be risk factors but now what variables determined celiac disease led researchers Drs. Hugh Reid and Professor Jamie Rossjohn of Monash University, Professor Frits Koning of the University of Leiden and Dr. Bob Anderson of biotechnology company ImmusanT Inc., to examine how the immune system senses gluten. They believe they have found an important breakthrough.
"This is the first time that the intricacies of the interaction between gluten and two proteins that initiate immune responses have been visualised at a sub-molecular level," Reid said.
ImmusanT is developing 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 for gluten and thus 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.
Anderson, Chief Scientific Officer at ImmusanT, says the research presents a unique opportunity.
"Because we now know the gluten peptides responsible for coeliac disease, we can interrogate the molecular events leading to a self-destructive immune response."
Research published in Immunity
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