53 in order to investigate potential differences in the antigens recognized. For example, while IgA dominates mucosal secretions, IgG is also detectable in the human intestines, with the IgG1 and IgG3 subclasses associated with inflammation compared to primarily IgG2 and IgG4 in healthy individuals.66 Similarly, DNA-sequence-based studies on BCR repertoires in CD have relied on peripheral blood mononuclear cells from the systemic circulation. Taking intestinal mucosal biopsies to obtain the resident B-lymphocytes for BCRseq could thus provide novel insights. Ultimately, combining DNA-sequence-based methods like BCRseq with functional antibody repertoire profiling methods such as peptide arrays or PhIP-Seq to detect the actual bound antigens could increase our understanding of the sequence–function relationship of antibodies, as well as improve diagnostics. Overall, the novel experimental directions outlined above have substantial potential to advance the field toward clinical implementations (Figure 3, Clinician’s Corner). For example, these methods may expose novel immunological targets in IBD that, by combining the optimal set of antigens, could outperform currently existing diagnostic tools (e.g. commercially available serological antibody panels). Such panels of biomarkers could, in turn, improve our current disease classification by shifting from traditional consensus- or symptom-based approaches toward molecular-data-driven patient stratification. For each clinical outcome, specific tailor- made combinations of serological antibodies could be established by examining them in close association with specific patient traits. Antibody signatures in IBD: developments and applications
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