Formation of ADAs in plasma was measured longitudinally at 4, 6, and 8 weeks by the Bethesda assay, which measures functional inhibition of clotting in the presence of neutralizing ADAs, and anti-FVIII IgG1 ELISA corresponding to human IgG4, the most prominent subtype in hemophilia A patients with high ADA titers (19, 40). Here, F8 is linked to hemophilia A.