Validating novel immune tests to support the diagnosis and monitoring of coeliac disease
Investigators: Assoc. Prof Jason Tye-Din (Walter and Eliza Hall Institute of Medical Research (WEHI)) and
Dr Robert Anderson (Wesley Medical Research).
Coeliac disease (CD) is a serious illness caused by gluten. We have shown that 1 in 70 Australians is affected by CD but only 1 in 5 are diagnosed, putting them at risk of health problems caused by ongoing gluten ingestion. Current tests to diagnose CD have many shortcomings, including the need for people to continue consuming gluten in their diet and an invasive procedure called a gastroscopy to collect samples of intestinal tissue currently needed to make a CD diagnosis. For patients with CD, monitoring of progress is best performed by gastroscopies however this is costly and invasive, and alternative approaches that rely on assessing symptoms or antibody levels in the blood fail to provide an accurate measure of how “active” the CD is.
CD is caused by the emergence of a small subset of cells in the immune system called gluten-specific T cells that specifically target fragments of gluten proteins. These “gluten-specific T cells” are needed for CD to develop and are not found in people without CD. In 2019, we were first to report that specific chemical markers called cytokines are rapidly produced by T cells and can be found circulating in blood with hours after people with CD consume gluten. Interleukin-2 (IL-2) is the most prominent cytokine elevated by gluten ingestion in CD. Increases of IL-2 in the bloodstream 3-4 hours after a meal of gluten is consumed is a very accurate marker for CD and its level also increases in proportion to the severity of adverse symptoms that develop. This important observation has since been independently replicated by two research groups with one showing that serum IL-2 measured 4 hours after gluten out-performed other diagnostic tests including small bowel biopsy (histology) in patients already established on gluten free diet.
Excitingly, we have recently shown that IL-2 produced when a blood sample is mixed with gluten in a test tube is also a sensitive marker of CD. Importantly, this test is accurate even when the person is following a gluten free diet. A key enabling step for these discoveries was the use of a special ultra-sensitive machine to detect IL-2. Our findings, now published in two journals, raise the prospect that this new blood test will provide a way to confidently diagnose CD in people who are strictly gluten free without the need for them to consume any gluten at all.
This study will assess how well these two approaches (IL-2 after gluten challenge, and IL-2 in a test tube of blood and gluten without oral gluten challenge) can diagnose CD and monitor it. We will study people with treated and untreated CD and also people without CD to determine how well these tests work and in whom. We will undertake immune studies to confirm it is the gluten-specific T cell producing the IL-2 and to work out the conditions for when the tests are most accurate.
The findings will provide crucial information on the role of a “T cell” immune test compared to traditional approaches to improve CD diagnosis and monitoring. The findings will be of exceptional relevance to the CD field and likely shape how people with CD are diagnosed and monitored in the future. A simple and accurate test for gluten-specific T cells will be a crucial enabling step for the field to advance a new definition of CD based on the presence of these cells, allowing it to move beyond a reliance on small intestinal biopsies and antibody markers.