Longitudinal monitoring of FVIII-specific antibodies and FVIII inhibitors in HIPS-ITI patient 1 during HIPS and HIPS-ITI. (A) FVIII-specific antibody titers (IgG1, IgG2, IgG3, IgG4, IgA, IgM as indicated) and FVIII inhibitors (BU/mL) for HIPS-ITI patient 1. The red dotted line represents the limit for positive evaluation of FVIII inhibitors (0.6 BU/mL). The yellow star marks the initiation of ITI treatment at ED11. The continuous vertical line indicates the end of HIPS and the start of HIPS-ITI. (B) Mean K_A for FVIII-specific antibodies differentiated for individual IgG subclasses and FVIII inhibitors (BU/mL) for HIPS-ITI patient 1. Data for apparent K_As include the 95% confidence intervals (CIs) for up to 2 affinity clusters for each IgG subclass (dark colors: cluster 1; light colors: cluster 2). The red dotted line represents the limit for positive evaluation of FVIII inhibitors (0.6 BU/mL). The asterisks mark antibodies with apparent affinities that were too high (K_As > 10¹¹ M⁻¹) to be assessed. Therefore, their apparent K_As were reported as 10¹¹ M⁻¹. The yellow star marks the initiation of ITI treatment at ED11. The continuous vertical line indicates the end of HIPS and the start of HIPS-ITI. ∗IgG1 cluster 1, ∗∗IgG4 cluster 1. B, baseline; ND, not detectable (below the detection limit of 1:20 for FVIII-binding antibodies).