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New research · Infectious Disease
Gut · 23h
Cohort studyGut · 2026

Deciphering the prodrome of inflammatory bowel disease up to 10 years before disease onset by massively parallel serology.

Arno R Bourgonje, Gabriel Innocenti, Alexandra Livanos … Saurabh Mehandru
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Infectious DiseaseCohort study

Immune changes linked to Crohn's disease onset up to 10 years prior.

Deciphering the prodrome of inflammatory bowel disease up to 10 years before disease onset by massively parallel serology.

Arno R Bourgonje et al. · Gut · 2026
Background

Defining immune dysregulation during the asymptomatic prodrome of immune-mediated diseases offers opportunities for early disease detection and interception.

Purpose

To define preclinical immunological alterations by characterising longitudinal serum antibody repertoires using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq).

Methods

We applied PhIP-Seq to profile antibody responses in 2000 longitudinal serum samples from 200 individuals who developed Crohn's disease (CD), 200 who developed ulcerative colitis (UC) and 100 matched healthy controls within the US military Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects cohort, collected up to 10 years before diagnosis.

n = 200 individuals
10
Results
years
Elevated immune responses were observed up to 10 years before Crohn's disease diagnosis.
n = 200 individuals
More results

Antibody repertoire variability was increased up to ~4 years prediagnosis in pre-CD and pre-UC individuals.

In contrast, responses to encapsulated bacteria (eg, Streptococcus pneumoniae , Haemophilus , Neisseria ) progressively declined towards diagnosis.

“
Conclusion

Large-scale serological profiling of archived prediagnostic samples identified disease-specific immune trajectories years before IBD onset, providing novel insights into disease pathogenesis in its prodromal phase.

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