Characterisation of the tolerant state in a patient with haemophilia B after removal of high-titre factor IX antibodies.
In a patient with severe haemophilia B and antibodies against factor IX in high titre, 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 intravenous 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. We have not been able to demonstrate an antiidiotypic antibody. 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.
Zettervall
O
O
Sundqvist
S B
SB
Nilsson
I M
IM
D000328:Adult; D001323:Autoantibodies / Q000302:isolation & purification*; D003520:Cyclophosphamide / Q000627:therapeutic use; D005164:Factor IX / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000097:blood* / Q000276:immunology / Q000628:therapy; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007167:Immunotherapy; D008297:Male; D012016:Reference Values; D005719:gamma-Globulins / Q000008:administration & dosage
D001323:Autoantibodies; D007136:Immunoglobulins; D005719:gamma-Globulins; D003520:Cyclophosphamide; D005164:Factor IX