Antibody Profiling Predicts Inflammatory Bowel Disease Years Before Diagnosis

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, involves abnormal immune responses that cause persistent inflammation and damage in the digestive system. However, the immune changes that precede diagnosis remain incompletely understood. Identifying these changes earlier could help clarify how the disease develops and who may be at risk. New findings offer insight into this prediagnostic period, showing that antibody patterns associated with IBD may be detectable years before diagnosis.

Presented at United European Gastroenterology (UEG) Week 2026 in Barcelona, the findings come from a large-scale study that used antibody profiling to examine immune changes before inflammatory bowel disease onset. The team analyzed antibody responses against approximately 357,000 microbial, viral, food, and immune-associated antigens. By tracking these responses across multiple time points before diagnosis, the researchers assessed how immune signatures evolved during the prediagnostic period.

The study analyzed 2,000 serum samples from 500 individuals, including 200 who developed Crohn’s disease, 200 who developed ulcerative colitis, and 100 age- and sex-matched healthy controls. Samples were collected at diagnosis and approximately two, four, and 10 years beforehand, allowing the team to track antibody responses over the decade preceding diagnosis.

Across these samples, researchers identified 123,980 unique antibodies. Antibody diversity was significantly lower in people who later developed either condition than in healthy controls. Beyond this overall reduction, distinct antibody responses associated with Crohn’s disease and ulcerative colitis were evident up to 10 years before diagnosis.

In Crohn’s disease, elevated antibody responses to herpesviruses and flagellin were observed, particularly among individuals who later developed complicated or ileal disease. Responses to encapsulated bacteria progressively declined as diagnosis approached. Ulcerative colitis showed a related but distinct pattern, with increasing antibody responses to herpesviruses and autoantigens alongside reduced reactivity to encapsulated pathogens.

Machine-learning models combining these early antibody signatures distinguished individuals who later developed Crohn’s disease or ulcerative colitis from healthy controls up to 10 years before diagnosis. Area under the curve (AUC) values were 0.90 for Crohn’s disease and 0.84 for ulcerative colitis. The profiles also differentiated individuals who later developed complicated versus noncomplicated Crohn’s disease approximately 10 years before diagnosis, with an AUC of 0.85.

“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,” said lead author Dr. Arno Bourgonje.

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

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