Owing to the higher incidence of ADAs in severe hemophilia A patients as compared to mild/moderate hemophilia A patients, the different level of FVIII deficiency might enlarge the FVIII-specific CD4 T cell repertoire from the already large repertoire found in healthy donors, by expanding T cells of higher avidity for their cognate antigen, a concept demonstrated for a tumor antigen in mice (114). Here, F8 is linked to neoplasm.