55 In a similar fashion, in-depth characterization of serological antibodies could also be performed with the goal of predicting patient response to medical and surgical therapies in IBD. As most medical treatments modulate certain immune pathways (e.g. TNF-α-antagonists, antiintegrin inhibitors, JAK inhibitors)67, combinations of specific antibody reactivities may confer predictive potential for this purpose. Likewise, the risk of the need for surgical interventions in IBD, the responsiveness to surgery and/or the risk of post-surgical complications might be predicted in an early stage using data-driven and validated selections of serological antibodies. Simultaneously, identification of aberrant antibody responses in IBD may also open up opportunities for immunotherapy. As alluded to above, patients with CD are marked by distinct antibody responses against bacterial flagellins, which have emerged as potential therapeutic targets. For instance, a recent study demonstrated that a combined treatment of cell activation and metabolic checkpoint inhibition (CAMCI) and a bio-engineered flagellin peptide (multiple flagellin T-cell epitopes, MEP1) resulted in ablation (cell death and anergy) of flagellin-reactive memory T-lymphocytes.68 Furthermore, this enhanced the corresponding regulatory subset of T-lymphocytes in mouse models of colitis. Subsequently, this treatment was able to induce scavenging of pathogenic T-lymphocytes in blood from patients with CD. Such an ingenious approach could be adopted to design and implement selective targeting of flagellin-reactive effector T-lymphocytes in patients with CD with high flagellin reactivity. This example illustrates that the identification of previously unknown antibody responses in patients with IBD could lay the foundation for targeted, personalized immunotherapy for specific subgroups of patients.69 Exposure of novel immunological targets would not only improve our understanding of IBD immunopathogenesis, it could also facilitate the early detection of IBD (pre-diagnostics, Figure 3). To this end, earlier studies14,16,26,36,37 could only use a selection of known serological antibodies, whereas emerging antibody profiling technologies have considerable potential to improve accuracy in predicting new-onset IBD. The detection of IBD in an early, preclinical stage would support the implementation of primary and secondary prevention strategies, e.g. lifestyle modifications or dietary interventions, as well as early initiation of (intensive) medical treatment so long as aspects such as cost-effectiveness, feasibility and risk/benefit ratios are favorable. Concluding Remarks A combination of disrupted intestinal barrier integrity and loss of immunological tolerance is believed to underlie IBD pathophysiology, resulting in the formation of aberrant mucosal and systemic immune responses. These immune responses may be responsible for the initiation and perpetuation of intestinal inflammation in patients with IBD. Serological indicators of these responses may be utilized for clinical purposes by developing or improving diagnostic, therapeutic and prognostic approaches. The recent advances reviewed in this article could improve our current understanding of disease pathophysiology while also providing a valuable resource of novel, previously unexposed immunological targets that may ultimately represent potent biomarkers in the context of IBD. Given the recent technological advances in high-throughput human antibody profiling, serological characterization of antibody epitope repertoires in patients with IBD deserves further investigation, preferably in large prospective longitudinal cohort studies (see Outstanding Antibody signatures in IBD: developments and applications
RkJQdWJsaXNoZXIy MjY0ODMw