No Gluten Required
Coeliac disease is a serious, autoimmune disease of the gut caused by a reaction to eating gluten. It causes damage to the lining of the gut and means that the body can’t properly absorb nutrients from food. It affects 1 in 100 people in Europe 1 but as only 30% of these are diagnosed, millions of people are struggling with unexplained symptoms, having the disease but unaware of it.
Gut biopsies and endoscopy
Coeliac disease is currently diagnosed in two parts; firstly a blood test to measure antibodies that the body makes in response to eating gluten and secondly, if this indicates a positive result, a gut biopsy to confirm. A gut biopsy is a simple but invasive procedure which involves an endoscopy into the small intestine where tiny samples of the gut lining are collected. These samples are then analysed by a pathologist to identify damage in the lining of the gut typical of the disease – an assessment that is not always clear cut.
Both of these tests only work if patients are still eating gluten. In fact, guidelines recommend that gluten is eaten in more than one meal every day for at least six weeks before testing. As the average time to gain a coeliac disease diagnosis is 13 years, a patient may already have adopted a gluten-free diet to manage symptoms so achieving a successful diagnosis requires them to return gluten to their diet. The irony, of course, is that eating gluten is what makes these patients ill in the first place. This often means that patients don’t (or can’t) eat enough gluten to make a positive diagnosis possible.
Immune repertoire profiling
That’s why scientists at Nonacus, together with researchers at the University of Cambridge led by Dr Elizabeth Soilleux, are working on the development of a new test for coeliac disease that works, 100% gluten-free. Funded by Innovate UK and Coeliac UK, this project is testing the use of immune repertoire profiling; sequencing the DNA of lymphocytes, the cells of the immune system involved in the bodies reaction to gluten. People with coeliac disease have lymphocytes with specific DNA profiles2 – and this profile doesn’t change, whether they have eaten gluten or not.
The test uses Nonacus Custom Cell3™ Target Panels to capture the lymphocyte DNA in gut biopsies prior to next generation sequencing. In conjunction with a bespoke computer algorithm (patent pending) it can identify patients with coeliac disease by predicting how likely their immune cells are to respond to gluten.
Predicting immune response to gluten
“What we are trying to do is make a new test that is based on the genetic code of lymphocytes, that allows us to look at a biopsy from someone who may or may not have coeliac disease and compare it to someone whom we are absolutely sure has the disease and compare it to the genetic code of their lymphocytes. And we are very hopeful that in the end we may not even need a biopsy but will be able to do this on a blood sample.” Dr Elizabeth Soilleux, Honorary Consultant in Pathology, University of Cambridge.
As well as providing a coeliac disease test for people who have already adopted a gluten free diet, the new test aims to improve on current methods of analysing biopsy samples by providing a more hard and fast answer. This will not only save considerable patient suffering but will also provide savings to the NHS, speeding up diagnosis journeys.
“Hopefully this project will bring us closer to having a test for coeliac disease for people who have already removed gluten from their diet and will be an improvement on the current methods, perhaps even leading to a non-invasive blood test as opposed to biopsy”, Chris Sale, CEO at Nonacus Ltd
Find out more about Nonacus Cell3™ Target library panels here
Hear more from Dr Elizabeth Soilleux here
- Mustalahti, K. et al. The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann. Med. 42, 587–595 (2010). https://doi.org/3109/07853890.2010.505931
- Yohannes, D.A., Freitag, T.L., de Kauwe, A. et al.Deep sequencing of blood and gut T-cell receptor β-chains reveals gluten-induced immune signatures in celiac disease. Sci Rep 7, 17977 (2017). https://doi.org/10.1038/s41598-017-18137-9