Figure 5. Pathogenic anti-C2 antibodies, but not anti-A2 antibodies, increase fVIII clearance in fVIII−/− mice.
(A) FVIII antigen levels were measured at 0.5, 1, 2, 4, and 8 hours after infusion of ~0.5 mg/kg anti-fVIII MAbs 4A4 (anti-A2 MAb), 3D12 (anti-C2 MAb), I109 (anti-C2 MAb), and 2–117 (anti-C2 MAb) followed by ~180 units/kg fVIII in fVIII−/− mice. Differences in fVIII antigen levels in MAb groups 4A4 (p = 0.62), 3D12 (p <0.001), I109 (p <0.001), or 2–117 (p = 0.26) compared to no MAb controls starting at 30 minutes and concluding at 8 hours was determined using non-linear regression to fit exponential decay models and the Sum of Squares Reduction test with Bonferroni method for multiple comparisons (significance level α= 0.007). (B) FVIII antigen levels two hours after fVIII infusion is compared to mice that received fVIII alone using Kruskal-Wallis test with Dunn’s correction for multiple comparisons. Data are presented as means with SD (n = 3–7 mice per group), * p < 0.05, ** p < 0.01, or *** p < 0.001