What if, in certain families affected by Crohn’s disease, the future could already be read in a simple blood test? North American researchers have just revealed, in the serum of relatives who are still asymptomatic, a very specific immune signature linked to this chronic inflammatory bowel disease.
Their study, published in the journal Clinical Gastroenterology and Hepatologysuggests that a Crohn’s disease blood test could identify people at high risk several years before diagnosis. A perspective that shakes up the way we think about screening and, perhaps one day, prevention.
A Crohn’s disease blood test for relatives at risk
Crohn’s disease is a chronic inflammatory condition of the digestive tract that causes persistent digestive symptoms, pain and fatigue, and significantly impairs quality of life. Its incidence in children has doubled since 1995 and continues to increase. In France, more than 200,000 people live with IBD such as Crohn’s disease or ulcerative colitis.
The blood samples were taken on average two and a half years before the appearance of the first digestive signs. Previous work had already shown that certain abnormal immune responses against intestinal bacteria (anti-flagellin antibodies) could be detected in people with Crohn’s disease. The idea is to see if these antibodies are present before the onset of the disease, and to determine whether this immune reaction can contribute to the onset of the disease, rather than being a consequence of it.
How this early blood biomarker works
The key to the test is IgG antibodies directed against flagellin, a protein that forms the “flagella” of many bacteria in the microbiota. In a healthy intestine, these microbes coexist with the host and participate in digestive balance. In Crohn’s patients, the immune system appears to abnormally target these normally beneficial bacteria. “We wanted to know: do people who are at risk, who are healthy now, have these antibodies against flagellin? We looked, we measured, and yes indeed, at least some of them had“, Dr. Ken Croitoru told MedicalXpress.
Of the 77 future patients, 28 already had high levels of anti-flagellin antibodies, or a little more than a third, with particularly strong responses among siblings, which reinforces the idea of shared environmental exposures. The researchers also showed that these antibodies, directed against a conserved domain of flagellin, were associated with markers of intestinal inflammation and an alteration of the intestinal barrier, two characteristics of Crohn’s disease. The average time between blood sampling and diagnosis of Crohn’s disease in people in the pre-disease phase was almost two and a half years.
Towards targeted screening and perhaps a vaccine
For Ken Croitoru, who holds the Canada Research Chair in inflammatory bowel diseases, the issue goes beyond simple prognosis: “With all the advanced biological therapies we have today, patient responses are partial at best. We haven’t cured anyone yet, and we need to do better“, he emphasized. His colleague Dr Sun-Ho Lee, clinician-scientist and gastroenterologist, added: “We discovered 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 in certain high-risk individuals for disease prevention. Validation studies and additional mechanistic studies are underway.”.
The authors point out that this early blood biomarker remains a research tool for the moment, and their results must still be confirmed in other cohorts. If these data are verified, this type of blood test could, however, tomorrow allow more precise monitoring of the most exposed relatives and pave the way for targeted prevention strategies against Crohn’s disease.