One in every three-hundred people has inflammatory bowel disease (IBD; comprising Crohn’s disease & ulcerative colitis) in the developed world and its incidence is rising fast in developing countries. In the UK alone there are around 620,000 sufferers with an annual cost to the NHS in excess of £1bn. Around half of patients have an aggressive, relapsing disease course, while in others the disease is more quiescent.
Unfortunately, prognostic markers that can reliably identify these patients are not available in clinical practice. This hinders disease management because patients with aggressive disease will be undertreated by conventional escalating dose therapy, while those with quiescent disease can be exposed to the risks and side-effects of unnecessary immunosuppression.
Research in the Department of Medicine found a transcriptional signature that is detectable within peripheral blood CD8 T-cells (a type of white blood cell) at diagnosis and which correlates with long term clinical outcome in IBD. The signature reflects a process called exhaustion, in which T-cells progressively lose the ability to sustain an effective immune response. Patients following an aggressive disease course have less exhaustion than those with a quiescent course. However, translating these findings to the clinic originally presented a technical challenge as blood cell populations needed separating to see a signal, something that is not practical in a routine clinical setting. To meet this challenge the researchers utilised novel approaches to find a whole blood biomarker that could provide the same results without the need for cell separation.
The answer was to measure gene expression using microarrays and then use machine learning to identify the suitable whole-blood biomarker. Ultimately this led to the identification of a 15 gene assay that could identify different disease courses by stratifying patients into aggressive and quiescent types of IBD, and an independent, prospective multicentre study validated these findings.
Having established these principles, a spin-out company (PredictImmune Ltd) was created through Cambridge Enterprise to translate this work into the clinic. The prognostic tests it provides for immune-mediated conditions can aid disease management and improve patient outcomes. As differing IBD patients may require different treatment regimens, the test ensures that they receive the most appropriate course of treatment and avoid excessive side effects resulting from over-treating the quiescent group, or excessive morbidity from under-treating the aggressive group. With funding from the Wellcome Trust, Predictimmune is also running a biomarker-stratified trial that is a first of its kind for inflammatory disease and will determine whether the biomarker can deliver personalised care.
The test uses a small blood sample to accurately predict each patients’ outcome at the point of diagnosis, and is available as a laboratory testing service and soon also as a kit. The group is also developing predictive tests for other immune-mediated diseases that pose long-term burdens on patients as well as imposing a financial burden society. They include tests for lupus, multiple sclerosis, diabetes mellitus and rheumatoid arthritis.
Professor Arthur Kaser