57 Clinician’s Corner Inflammatory bowel diseases (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases of the gastrointestinal tract that are characterized by aberrant immune responses compared to healthy individuals. Inadequate intestinal barrier function in IBD leads to uncontrolled passage of luminal antigens that would otherwise not be recognized by the immune system. This phenomenon largely explains the existence of serological antibody signatures in patients with IBD, in particular the formation of antimicrobial antibodies. Well-established serological antibodies for IBD include anti-Saccharomyces cerevisiae antibodies (ASCA, mainly in CD) and perinuclear anti-neutrophil cytoplasmic antibodies (pANCA, mainly in UC), among others. Although these antibodies show strong associations to relevant clinical phenotypes and outcomes, their sensitivity is relatively low compared to their specificity, rendering their clinical utility rather limited. Serological testing is therefore currently not recommended for routine diagnostic assessment of IBD. Recently, novel innovative antibody profiling technologies have been emerging that may expose novel immunological markers for IBD in a high-resolution, high-throughput fashion. Compared to conventional ELISAs, which can test dozens to hundreds of antigens, highthroughput methods such as peptide arrays and PhIP-Seq can test thousands to hundreds of thousands of antigens in parallel. These emerging antibody profiling technologies have the potential to transform into useful clinical applications,whichwouldhelptoachievea largenumberof clinically relevant endpoints in IBD. For example, selected combinations of serological antibodies could help improve disease subtyping and classification and the prediction of disease flares, disease progression and therapeutic response (to both medical and surgical interventions). Furthermore, antibody signatures may be targets for (immuno)therapeutic interventions. Finally, this antibody-driven disease characterization may aid in the early detection of IBD in at-risk individuals from the general population, which would open up opportunities for primary and secondary diseaseprevention strategies. Antibody signatures in IBD: developments and applications
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