Antibody responses predict IBD onset 10 years before diagnosis

High-throughput and high-resolution antibody profiling might help to unravel the complex landscape of serological responses in patients with inflammatory bowel disease (IBD), offering insights that can be used to predict disease onset early and accurately.

A recent study applied a large-scale approach to characterise antibody epitope repertoires in patients with IBD, revealing a diversity of disease-specific antibody responses against microbes, viruses, food particles, and self-antigens [1]. To pinpoint the earliest immunological alterations that precede disease onset, Dr Arno Bourgonje (University Medical Center Groningen, the Netherlands) and co-investigators aimed to characterise antibody epitope repertoires in the pre-clinical phase of IBD [2].

The investigators collected data from 200 participants with Crohn’s disease (CD), 200 participants with ulcerative colitis (UC), and 100 healthy controls who were enrolled in the longitudinal pre-clinical PREDICTS cohort. “We had serum samples of these individuals at 10 years, 4 years, and 2 years before the diagnosis, as well as around the time of diagnosis,” added Dr Bourgonje. Using phage-display immunoprecipitation sequencing (PhIP-Seq), the authors profiled antibody epitope repertoires against 357,000 peptide antigens.

The results revealed that antibody epitope repertoires in patients with pre-clinical IBD showed reduced diversity towards diagnosis. At diagnosis, antibody responses against herpes viruses were increased, whereas antibody responses against Streptococcus were reduced in frequency, compared with 10 years pre-diagnosis, among patients with CD. The corresponding findings in patients with UC were that antibody responses against herpes and influenza viruses were higher towards diagnosis, whereas anti-rhinovirus responses were lower. Furthermore, antibody epitope repertoires profiled 10 years pre-diagnosis could accurately predict CD onset (AUC 0.90) and UC onset (AUC 0.84).

“The data shown today only represent the tip of the iceberg,” ended Dr Bourgonje. “This data allows for novel insights into IBD pathogenesis and disease prediction.”

1. Bourgonje AR, et al. Immunity. 2023;56(6):1393-1409.e6.
2. Bourgonje AR. Systematic antibody responses predict the onset of inflammatory bowel disease up to 10 years before diagnosis. OP01, 20th Congress of ECCO, 19–22 February 2025, Berlin, Germany.

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Posted on 8 April 2025