By analysing pre-diagnostic blood samples from the LifeLines Cohort Study, the investigators identified antibody signatures that precede the onset of inflammatory bowel disease (IBD) . Their findings are published in the journal Gut.
Following their prior study published in Immunity in 2023, in which the authors identified specific IBD associated antibody profiles, they now analyzed antibody repertoires in individuals who later in life developed IBD. By screening over 167,000 participants in LifeLines, 178 individuals were identified who eventually developed IBD within roughly four years of follow-up. Using a high-throughput technique called phage-display immunoprecipitation sequencing (PhIP-Seq), the team screened each individual’s blood against ~344,000 possible antigens from microbes, viruses, food, and human proteins. This approach revealed over 5,000 distinct antibody responses and pinpointed several dozens that changed significantly between pre-diagnosis and post-diagnosis periods, of which some were already-known IBD-related antibodies while the remainder constituted newly identified changes around disease onset.
The study uncovered both shared and disease-specific immune patterns. One common change was a decrease in certain antiviral antibodies after IBD diagnosis. For example, patients showed reduced antibody responses to Epstein–Barr virus (EBV) and other herpesviruses. However, Crohn’s disease and ulcerative colitis also showed distinct signatures. Individuals who later developed Crohn’s had higher antibody reactivity against bacterial flagellin proteins years before any symptoms. In contrast, people who developed ulcerative colitis displayed elevated antibody responses to specific viruses (e.g. adenovirus, enteroviruses) and bacteria only after their disease had started.
This study is the first high-resolution analysis of antibody changes during the transition from health to IBD. The findings provide novel insights into the immunological events preceding Crohn’s disease and ulcerative colitis, highlighting potential biomarkers for early diagnosis. Detecting these preclinical antibody signatures could enable physicians to identify at-risk individuals before symptoms occur, allowing closer monitoring or even potential preventive measures. In other autoimmune conditions like rheumatoid arthritis and type 1 diabetes, such pre-symptomatic antibody tests have already helped select individuals for early therapeutic intervention. These advances point to a future where IBD might potentially be intercepted before it causes irreversible intestinal damage. Large European efforts (EU-IHI INTERCEPT Program) are currently ongoing to work towards this through developing biomarker predictions models for early identification of IBD and subsequent therapeutic interception.
