Jason Tye-DIn-Projects

Jason Tye-DIn-Projects

Projects

If you are interested in participating in or learning more about our studies, please email coeliac@wehi.edu.au or call +61 3 9345 2300 and leave a message.
Super Content: 
Dr Jason Tye-Din and Dr Melinda Hardy holding oats in lab

We have discovered how oats incite a harmful immune response in 8 per cent of people with coeliac disease

How does gluten make people with coeliac disease and gluten sensitivity sick?

Our studies in adults and children with coeliac disease have provided detailed knowledge of the key parts of gluten harmful to people with coeliac disease. However, how gluten triggers adverse symptoms such as vomiting, pain or diarrhoea in people with coeliac disease remains poorly understood.

This study will examine immune responses in the blood stream and small intestine after people with coeliac disease, gluten sensitivity and healthy volunteers consume a small meal containing gluten. Testing will involve a detailed study of the immune cells and employ a variety of advanced approaches including examining which genes are turned on. The results will provide a unique insight into how symptoms occur to gluten and potentially define targets suitable for treatment to better manage symptoms. The study will also validate the role of cytokine measurement as a diagnostic test in coeliac disease and biomarker linked to symptoms.

Are oats toxic in coeliac disease?

The safety of oats for people with coeliac disease is controversial. Australia and New Zealand exclude oats from the gluten-free diet due to safety concerns, but many other countries do not. Oat is a nutritious grain that is high in fibre and may have a range of health benefits, but it is important to determine if they can be safely consumed by people with coeliac disease.

We have shown that almost 10 per cent of people with coeliac disease have T cells that are triggered by oats to promote an inflammatory response, potentially putting them at risk of harm. This study aims to definitively determine if oats are safe to consume in coeliac disease, if safety can be determined by an immune blood test or food test, and whether a specific type or dose of oats is necessary for safe consumption.

This study will involve the consumption of contamination-free oats or oat protein, immune blood tests and for some, gastroscopy and biopsy of the small bowel.

Establishing the clinical benefit of a genomic tool for people with coeliac disease

The information in a person’s whole genetic code (genome) has enormous potential for being used to improve that individual’s medical care and treatment. A genomic test for people with coeliac disease is particularly appealing as this illness has a strong genetic component.

In collaboration with Professor Mike Inouye, Dr Gad Abraham and team (Baker Institute) we are validating a genomic risk tool that can help identify people at higher risk of developing coeliac disease more accurately than the current HLA-DQ2/8 gene test.

This study will examine the usefulness of this tool in a large number of people who have coeliac disease, are related to someone with coeliac disease or are non-coeliac controls. The tool may help identify which person, for example a relative, is at high-risk for coeliac disease development and needs closer monitoring. Genomic information may also provide insights into how coeliac disease may behave over time, such as those at higher risk of developing specific complications.

We aim to use this information to guide and improve medical care.

Why does the gluten free diet fail?

The gluten-free diet is the main treatment for coeliac disease, yet many patients continue to have intestinal damage or experience symptoms despite many years on the diet. Ongoing intestinal damage is concerning as it is associated with a higher rate of complications such as osteoporosis, infections, refractory coeliac disease and cancers such as lymphoma.

This project is investigating the reasons why the gluten-free diet fails in some patients despite their best attempts to exclude gluten. While it is assumed that low amounts of inadvertent gluten exposure is responsible for dietary failure, the actual causes for this have not been systematically addressed. This study is exploring the role of gluten contamination in commercial gluten-free foods and gluten-free products sold in food outlets, examining food handling, labelling and testing practices in industry, and looking at patient factors that contribute to knowledge and compliance to the diet.

The findings will inform targeted strategies to improve gluten-free diet outcomes for people with coeliac disease. 

What is the role of the microbiome in coeliac disease?

While specific genes, such as HLA-DQ2 and/or HLA-DQ8, are critical for the development of coeliac disease, environmental factors are also considered important, possibly as ‘triggers’ of disease. How they might do this is a very important question.

Emerging evidence suggests an important role for the eco-system of microbial organisms in the gastrointestinal tract, termed the ‘microbiome’.  For example, studies undertaken with collaborators Professor Elena Verdu (McMaster University, Canada) and Professor Jamie Rossjohn (Monash University) have implicated Pseudomonas bacteria in coeliac disease via a number of different mechanisms. The research raises the possibility that specific alterations in the microbiome may have an important effect on gluten immunity and could affect the risk for coeliac disease development in genetically susceptible people.

Assessing spleen function and infection risk

The spleen plays a crucial role in antibody generation and defense from infections.

In people with coeliac disease, spleen function can be impaired (‘hyposplenism’), but the size of this issue is unclear and there is no Australian information. Hyposplenism is associated with higher rates of infections, including serious ones such as pneumococcal pneumonia.

This study is assessing spleen function in people with newly diagnosed and treated coeliac disease to determine how hyposplenism affects immune function, the risk of infections and adequacy of vaccination responses. 

Assessing non-invasive tools that measure accidental gluten intake

Establishing how well a person is following a gluten free diet is difficult. Current tools rely on assessing a person’s diet or using antibody tests or intestinal biopsy, but these only indirectly reflect gluten exposure and they are not very helpful at determining if gluten is still being consumed.

This study is assessing a new technology designed to objectively measure the presence of gluten (specifically, fragments of gluten called peptides) in a person’s stool (faeces) or urine. This test, called a gluten immunogenic peptide (GIP) assay, is highly sensitive for detecting tiny amounts of gluten ingested by a person. They offer the potential to help doctors determine when a person with coeliac disease who is following a gluten free diet is actually consuming gluten. This randomised, double-blind study aims to determine the best way to use these tests to detect gluten exposure which can provide valuable information for the patient and treating doctor.