The classic case is hemophilia A and B, where patients lack all or part of the factor VIII (FVIII) or factor IX procoagulant proteins, respectively, and therefore have never “acquired” tolerance to that protein as “self.” Prophylactic or on-demand treatment of bleeds with recombinant or plasma-derived FVIII can lead to an antibody response to this human (but “foreign”) protein that effectively neutralizes or inhibits its function in the coagulation pathway; these antibodies are called “inhibitors.” The gene discussed is F8; the disease is hemophilia A.