SPIT Study - Diagnosing Crohn's disease based on salivary epigenetics
Prof. Laurence Lovat
Institution or company
University College London
Gastroenterology, Genomics and Rare Diseases
Crohn’s disease (CD) may be difficult to diagnose, particularly in patients with predominantly small bowel disease and specifically in teenagers and young adults who are generally uncomfortable about having invasive tests such as colonoscopy. The aim of this research proposal is to investigate a completely novel and non-invasive way to identify those with the disease.
DNA carries not only genetic information but also switches which enable cells to turn particular genes on and off. These DNA sequences are called epigenetics. Lymphocytes, white blood cells, are important in CD. These carry epigenetic information around the body and are secreted into saliva.
The hypothesis is that the epigenetic switches found in saliva may be used to identify changes occurring in the body that can be used to predict the presence or absence of Crohn’s disease.
We wish to collect fasting saliva samples. We will create cohorts of patients with new diagnosis Crohn’s or recent diagnosis of Crohn’s and non-genetically related controls matched by age, sex and ethnicity.
We will extract DNA from saliva samples and assess sample quality. Suitable DNA samples will be prepared and analysed for 850,000 epigenetic locations throughout the genome. The resulting raw data will be analyzed using standard and novel tools to identify differences in epigenetic expression between patients and normal controls.
A suitably sized panel of epigenetic markers will be constructed to give a high accuracy for detecting people with Crohn’s disease and distinguishing them from people who do not have Crohn’s. The panel’s utility will be confirmed in an independent second cohort of CD patients and controls. The impact of a successful outcome will be a completely non-invasive, simple to administer test for diagnosing or screening for Crohn’s disease.
As no test has 100% accuracy, the precise role of this new test will need to be defined, but it is likely that it will act as a first line screening test to identify individuals who have a high risk of having Crohn’s and in whom further invasive tests are warranted - whilst strongly reassuring the physician and low-risk patients that no further tests need to be undertaken. This will allow better targeting of scarce resources with faster access to diagnostic tests, better acceptance and higher compliance particularly amongst young people with the improved diagnostic pathway.