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. 2018 Dec 4;104(2):236–244. doi: 10.3324/haematol.2018.206383

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Figure 2. — Immune response to factor VIII in patients with severe hemophilia A. (A) Classically, deciphering the immunogenicity of therapeutic factor VIII (FVIII) in patients with severe hemophilia A is addressed by investigating the reasons for which 20-30% of the patients develop an immune response to exogenous FVIII, while the remaining patients do not (adapted from Gouw et al.).²⁴ (B) We propose that the immune system of all patients treated with FVIII reacts to the clotting factor. In 70-80% of the cases, this immunological assessment of therapeutic FVIII results in the establishment of active immune tolerance that relies on an equilibrium between FVIII-specific immune effector and regulatory elements. However, for reasons that are yet to be deciphered, the remaining patients fail to turn on appropriate anti-inflammatory/tolerogenic mechanisms. Anti-FVIII IgG: anti-factor VIII immunoglobulin G; aFVIII T cell: factor VIII-reactive T cell; Treg: regulatory T cell; anti-Id IgG: anti-idiotypic immunoglobulin G.