See one arrive
Crohn’s disease several years before the first abdominal cramp: for Canadian researchers, this scenario no longer belongs only to science fiction. They describe a simple blood test able to identify people at high risk when they do not yet have any symptoms.
Faced with harmless bacteria, the immune system goes haywire
Crohn’s disease is a chronic inflammation of the digestive tract that causes persistent diarrhea, pain, fatigue and significantly impairs quality of life. Its incidence in children has doubled since 1995 and cases continue to increase. However, scientists have just identified a discreet signal in the blood, detectable well before the first outbreak. “Despite all the cutting-edge biological treatments available to us today, patient responses are partial at best. We haven’t cured anyone yet and we need to do better.”said Ken Croitoru of the University of Toronto and Canada Research Chair in inflammatory bowel disease.
The work of Dr Ken Croitoru’s team is part of the CCC-GEM project, which has been following more than 5,000 first-degree relatives of Crohn’s patients since 2008. Since 2008, this project has collected genetic, biological and environmental data to better understand the development of the disease. To date, 130 of these volunteers have developed the disease.
Previously, researchers had found that an inflammatory immune response directed against intestinal bacteria could occur well before Crohn’s disease manifests. In healthy individuals, these bacteria live in harmony in the gut and are crucial to maintaining good digestive health. However, in Crohn’s disease, the immune system appears to react inappropriately against normally beneficial microbes. researchers at the University of Alabama had developed a test capable of detecting antibodies against flagellin (a protein which forms the “engine” of certain intestinal bacteria) and had shown that people with Crohn’s disease had high levels of antibodies targeting the flagellin of bacteria Lachnospiraceae .
This blood test predicts Crohn’s disease 2.5 years before diagnosis
The Toronto researchers then asked themselves a simple question: “We wanted to know: do people who are at risk, who are healthy now, have these antibodies against flagellin?” said Dr. Croitoru.
In this substudy, 381 first-degree relatives of patients were followed; 77 subsequently developed Crohn’s disease, compared to 304 controls who remained unaffected. Among these 77 future patients, 28 already presented a high antibody response against flagellin, or a little more than a third, even though they declared themselves to be in good health. The strongest responses were observed among siblings, suggesting the weight of a shared environment. The scientists also verified that this pre-illness reaction to Lachnospiraceae flagellin was linked to intestinal inflammation and intestinal barrier dysfunction, two hallmarks of Crohn’s disease.
On average, the diagnosis of Crohn’s was established approximately two and a half years after the blood test was performed.
Towards a future vaccine against Crohn’s disease?
For gastroenterologist Dr Sun-Ho Lee, this signal opens a new window on the silent phase of the disease: “Confirmation of our previous study on the immune response against bacterial flagellins shows strong associations with future risk of Crohn’s disease in healthy first-degree relatives“, said Dr. Lee. “We found that this immune response is induced by a conserved domain of the flagellin protein. This paves the way for the design of a vaccine targeting flagellin to prevent the disease in certain high-risk individuals. Validation studies and additional mechanistic studies are underway“.
Concretely, these results describe a blood biomarker capable of announcing the onset of Crohn’s disease approximately two and a half years before the first signs in people already considered at risk. The test remains used as part of vast international research, but it outlines a future where we could monitor, and perhaps protect, more closely the families affected by this growing digestive pathology.