Characterisation of the tolerant state in a patient with haemophilia B after removal of high‐titre factor IX antibodies

Abstract

In a patient with severe hemophilia B and antibodies against factor IX in high titer, and known for many years to be a really high responder, it was possible to suppress the secondary antibody response after treatment with high doses of i.v. IgG (Gammonativ, KabiVitrum AB) combined with factor IX and cyclophosphamide. After 2 further treatments, including IgG, a total disappearance of the IX:C inhibitor was noted. The patient now treats himself at home with weekly infusions of only factor IX concentrate. Survival of IX:C is normal, though IX antigen (IX:Ag), as measured with the original antibody in an immunoradiometric assay, persists for at least a week after concentrate infusion. An antiidiotypic antibody was not demonstrated. Instead, the antigenic factor IX material circulates complexed to a new antibody without anticoagulant activity. Theoretically at least, the persistence of such immune complexes may be important for sustaining the patient''s tolerance to the anticoagulant antibody''s epitope. The initial IgG treatment appears as a crucial factor for induction of tolerance in this case.