Longitudinal monitoring of FVIII-binding antibodies and FVIII inhibitors in 2 representative examples of patients in subgroup 4. (A-B) Results of the analysis of FVIII-binding antibodies (IgG1, IgG2, IgG3, IgG4, IgA, and IgM, as indicated) and FVIII inhibitors (BU/mL) for 2 representative examples of patients in subgroup 4, patient 17 (A) and patient 21 (B), who developed FVIII-binding IgG subclass-switched antibodies and persistent FVIII inhibitors. The red dotted lines represent the limit for positive evaluation of FVIII inhibitors (0.6 BU/mL). (C-D) Apparent affinity constants of FVIII-binding antibodies (mean K_A), differentiated for individual IgG subclasses and FVIII inhibitors (BU/mL), in patient 17 (C) and patient 21 (D). Data for apparent affinity constants include the 95% CIs for ≤2 affinity clusters for each IgG subclass (open bars, population 1; closed bars, population 2). The red dotted lines represent the limit for positive evaluation of FVIII inhibitors (0.6 BU/mL). The asterisk indicates antibodies with apparent affinities that were too high to be assessed. Therefore, they were set to 10e11. The data for the remaining 5 patients of subgroup 4 are shown in supplemental Figure 4.