Deciphering the prodrome of inflammatory bowel disease up to 10 years before disease onset by massively parallel serology.
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.
Defining immune dysregulation during the asymptomatic prodrome of immune-mediated diseases offers opportunities for early disease detection and interception.
To define preclinical immunological alterations by characterising longitudinal serum antibody repertoires using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq).
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 (ulcerative colitis) and 100 matched healthy controls within the US military Proteomic Evaluation and Discovery in an inflammatory bowel disease Cohort of Tri-service Subjects cohort, collected up to 10 years before diagnosis.
Antibody repertoire variability was increased up to ~4 years prediagnosis in pre-CD and pre-ulcerative colitis individuals.
In contrast, responses to encapsulated bacteria (eg, Streptococcus pneumoniae , Haemophilus , Neisseria ) progressively declined towards diagnosis.
Large-scale serological profiling of archived prediagnostic samples identified disease-specific immune trajectories years before inflammatory bowel disease onset, providing novel insights into disease pathogenesis in its prodromal phase.