In the described study we analyzed the anti-infliximab antibody response in pediatric patients with JIA treated with infliximab. Similarly to other studies in adults we found that antibodies to infliximab (ATI) developed in 43% of the patients. We also observed that the formation of ATI is associated with decreased infliximab serum trough levels, which is the most likely cause of the and a loss of infliximab efficacy. The majority of our efforts were focused on elucidating where on the infliximab molecule the ATI bind. As predicted, we observed that the majority of ATI bind the variable regions of infliximab, which are the regions where the amino acid residues of murine origin can still be found. To define the binding sites, or epitopes, of these ATI more precisely, we tried a number of different methods for epitope mapping. However, none of the methods that we used in our study proved to be successful. We attributed our shortcomings to the finding that all of the antibody epitopes were composed of discontinuous segments of infliximab only coming into proximity to one another in the folded conformation. Discontinuous epitopes are much more difficult to map, as there are few methods to do so and those methods that exist do not always yield reliable results.
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