49 Prediction of therapeutic response in IBD In the therapeutic management of IBD, it is notoriously challenging to predict which patients will benefit most from which type of medical treatment, a challenge mainly due to the heterogeneity of the disease and, consequently, patients’ therapeutic responsiveness, particularly to biologicals. For instance, up to 30–40% of patients demonstrate non-response or loss-of-response after induction therapy with TNF-α-antagonists (e.g. infliximab) and approximately 40–50% of patients fail to respond to induction therapy with the α4β7-integrin inhibitor vedolizumab.43,44 Serological antibodies have therefore alsobeen evaluated for their capacity topredict response to treatment in IBD. For instance, pANCA-positive but ASCA-negative patients with CD demonstrated little benefit from treatment with TNF-α-antagonists.45,46 Likewise, pANCA-positive/ASCA-negative patients with UC previously showed decreased response rates to TNF-α-antagonists.47 Another study found that patients with CD who were positive for anti-OmpC or anti-I2 antibodies responded better to antibiotic treatment.13 Anti-GP2 and anti-IFI16 antibodies have been associated with non-responsiveness to infliximab and the need for surgical intervention in CD.48,49 Currently, however, the evidence is still insufficient to recommend the use of serological antibodies to predict patients responses to particular medical treatments or surgical interventions in IBD.35 Antibody Profiling Techniques: the State of the Art While most of the serological antibodies in IBD listed in Table 1 were identified using conventional enzyme-linked immunosorbent assays (ELISAs), several more-advanced antibody profiling technologies have emerged50 that have provided unprecedented insights into antibody repertoires in IBD (Figure 2). ELISAs, similar to radioimmunoassays (RIAs), are typically based on the immobilization of antigens on surfaces and subsequent detection of antibody binding by enzymatic (in ELISA) or radiolabeled (in RIA) signal amplification. These methods yield high sensitivity/specificity and can be used for absolute quantifications in combination with calibration curves. ELISAs can be run on thousands of samples. Typically, only the antibody binding against a single antigen is assessed, making parallel measurements against multiple antigens challenging and limiting ELISAs to the analysis of a few antigens in diagnostic settings. Antibody signatures in IBD: developments and applications
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