Immune changes could signal inflammatory bowel disease up to 10 years before diagnosis

A large-scale study, presented at UEG Week 2026, has identified distinct antibody patterns up to 10 years before the diagnosis of inflammatory bowel disease (IBD), potentially opening new avenues for earlier risk detection and providing insights into future disease course.

IBD is a group of chronic conditions, including Crohn’s disease (CD) and ulcerative colitis (UC), in which abnormal immune responses contribute to ongoing inflammation and damage in the digestive system. Although IBD is increasingly recognized to develop over a prolonged period before diagnosis, relatively little is known about the immune changes that occur during this time.

To investigate these changes, researchers analyzed 2,000 serum samples from 500 individuals, including 200 who developed CD, 200 who developed UC and 100 age- and sex-matched healthy controls. Samples were collected at diagnosis and approximately two, four and 10 years beforehand.

The researchers profiled antibody responses against around 357,000 microbial-, viral-, food- and immune-associated antigens, allowing them to examine antibody patterns in the years leading up to diagnosis.

Antibody changes emerge a decade early

Across the 2,000 samples, researchers identified 123,980 unique antibodies. Compared with healthy controls, antibody diversity was significantly lower in people who later developed CD or UC, with distinct antibody responses evident in both conditions up to 10 years before diagnosis.

In CD, elevated responses against herpesviruses and anti-flagellin antibodies were observed, particularly in people who later developed complicated or ileal disease, while responses to encapsulated bacteria progressively declined toward diagnosis.

In UC, rising antibody responses against herpesviruses and autoantigens were accompanied by reduced reactivity to encapsulated pathogens.

Models distinguish future disease and complications

When these early antibody signatures were integrated using machine-learning models, they discriminated people who would later develop CD or UC from healthy controls up to 10 years before diagnosis, with area under the curve (AUC) values of 0.90 and 0.84, respectively.

The profiles also differentiated people who later developed complicated from noncomplicated CD up to approximately 10 years before diagnosis, with an AUC of 0.85.

Commenting on the findings, lead author Dr. Arno Bourgonje said, “It is fascinating to see that complicated CD at diagnosis is associated with a distinct antibody profile years before the first clinical symptoms and is not simply the consequence of disease progression after diagnosis.

“Finding these patterns so early points to the potential of antibody profiling to support earlier risk detection, distinguish between disease subtypes and help identify patients who may benefit from more intensive therapy as early as possible.”

Validation needed before clinical screening

The authors note that while the findings provide an important proof of principle, further research is needed before they can be translated into a clinical screening test.

“The next priority is to validate these signatures in independent, more diverse and prospectively followed populations,” concluded Bourgonje.

“We also need to determine their added value alongside genetic, clinical and other blood-based markers, translate the findings into a reproducible and affordable targeted assay and, ultimately, demonstrate that using such a test actually leads to better clinical outcomes.”

Provided by
United European Gastroenterology

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

Full profile →

Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

Full profile →