The potential of data for managing chronic disease
Inflammatory bowel disease and long term profiling
What is inflammatory bowel disease?
Inflammatory bowel diseases (IBD)- ulcerative colitis (UC) and Crohn’s disease (CD), are autoimmune conditions that primarily affect the gut. Autoimmune diseases like IBD and rheumatoid arthritis are what happens when the immune system goes rogue and starts reacting to cells and/or tissues in our body. Our immune system should ignore our healthy cells, tissues and resident microbes (microbiota) and not react to them. In an autoimmune disease somehow this don’t happen and our immune cells react to our cells just as if they were pathogenic threats.
IBD is associated with an in appropriate reaction to the gut microbiota and results in chronic (long term) inflammation and damage to the gut. IBD is on the rise across the world with at least 6.8 million cases globally. Although the abbreviations may make the terms sound similar, IBD is completely distinct from IBS (irritable bowel syndrome). IBS, although unpleasant, does not necessarily involve immune cells and can be caused by a multitude of factors including stress and diet that affect how we digest our food and can cause changes in bowel movements and bloating.
Currently there is no cure for IBD and most treatments try to limit the inflammation and the subsequent damage this causes. However, the treatments do not prevent IBD and the drugs may stop being as effective which can cause symptoms to relapse. Ultimately, some people will need life-changing surgery.
Like many autoimmune diseases, we still don’t really fully understand why some people get IBD and others don’t. Autoimmune conditions are typically a combination of genetic susceptibility to a condition alongside environmental factors that come together to cause someone to get an autoimmune condition. We have learned so much about IBD over the last 20-30 years and the role of the immune system. Although this has helped design better therapies to manage the symptoms of IBD, it doesn’t necessarily help determine who will get the disease and why.
Diagnosis of IBD relies on a combination of things including changes in the blood, symptoms and colonoscopy. However, by the time diagnosis is made, the person may already have quite severe symptoms and damage to their gut and there has long been a desire to find ways to screen for IBD before the damage is done. New research out this week has taken a step in this direction. Data was accessed from a Danish cohort of approximately 20,000 IBD patients (and 4.6 million potential population-based controls). They looked at records of blood tests that were taken annually up to 10 years before IBD was diagnosed and compared these with healthy bloods over the same time. Several things were assessed; markers of inflammation (CRP or c-reactive protein and F-cal or faecal calprotectin), vitamins and minerals, liver function and levels of leukocytes (white blood cells).
What the figure below shows you is that there are changes in the blood WAY before IBD is diagnosed. The things in blue are things that go down whereas the things in red are increased relative to controls. The more intense the colour, the greater the change.
The overall numbers of leukocytes were higher several years before diagnosis with IBD. We have lots of different leukocytes and, in both CD and UC, there were early increases in our rapid responder immune cells- cells like monocytes and neutrophils. The lymphocytes also increased but much later. This could suggest inflammation developing and consistent with this was the observation that inflammatory markers like CRP and f-Cal increased. The patterns in CD versus UC differed with UC only showing changes a few years before diagnosis. However, there is a huge caveat with these findings as although there were changes in blood markers over time, these changes were STILL within normal parameters. As such, they would not be flagged in routine tests.
The researchers checked whether a combination of these changes over time could help with diagnosis. A combination of results did show potential to help narrow an earlier diagnosis in both with CD having the greatest certainty. However, a limitation of this study is that we don’t know why these individuals were being screened and how specific such results are. For example, patients may have had other inflammatory conditions. Further studies will have to be done.
This research is still incredibly exciting and important though. This type of approach of longitudinal analysis over time could be really useful with a potential to transform patient care- picking up patients much earlier and intervening before they get very sick which could really help their quality of life. Training will be needed to ensure medical professionals can work confidently with the data. However, ss with all things though, there is a need to consider how to use such data responsibly, equitably and ethically.