Pathogenic immune response to therapeutic factor VIII: exacerbated response or failed induction of tolerance?

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Antibodies to factor VIII. V. Patterns of immune response to factor VIII in hemophilia A.

The natural history of factor VIII antibodies was studied in 20 severe, multitransfused hemophiliacs. Two patterns of humoral immune reactivity were observed. In one group of ten, who developed antibodies after an average of 22 cumulative exposure days to factor VIII, the antibody titers increased after each antigenic stimulation or persisted for years in the absence of transfusion. These patie...

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A role for thrombin in the initiation of the immune response to therapeutic factor VIII.

Administration of human factor VIII (FVIII) to FVIII knockout hemophilia mice is a useful small animal model to study the physiologic response in patients iatrogenically immunized to this therapeutic protein. These mice manifest a robust, T cell-dependent, antibody response to exogenous FVIII treatment, even when encountered through traditionally tolerogenic routes. Thus, FVIII given via these ...

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Induction of tolerance to human factor VIII in mice.

This paper reports loss of human factor VIII (hFVIII) inhibitory antibody in immunocompetent C57BL/6 mice. High-titer anti-hFVIII antibody developed in the mice within 7 to 14 days of intraportal administration of adeno-associated virus (AAV) carrying FVIII that coincided with a reduction in plasma hFVIII antigen. Bethesda titers (> 100 units) persisted relatively unchanged for 9 to 10 months. ...

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Case report: induction of immune tolerance to factor VIII inhibitor after a major operation.

INTRODUCTION We report a successful case of immune tolerance to factor VIII (FVIII) inhibitor after a major operation. An attempt was made to induce immune tolerance with inhibitor in a haemophilia A patient, who was required to undergo an above-knee amputation. We opted to give high-dose FVIII infusion with no immunosuppression. OUTCOME The highest preoperative FVIII inhibitor level was 5 BU...

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Noncoagulation inhibitory factor VIII antibodies after induction of tolerance to factor VIII in hemophilia A patients.

We recently described tolerance induction with factor VIII/IX, cyclophosphamide, and high-dose intravenous IgG in hemophilia A or B patients with coagulation inhibitory antibodies. Circulating noninhibitory antibodies complexed with factor IX have been demonstrated in tolerant hemophilia B patients. Similar findings are now described in six tolerant hemophilia A patients. Complexes between fact...

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ژورنال

عنوان ژورنال: Haematologica

سال: 2018

ISSN: 0390-6078,1592-8721

DOI: 10.3324/haematol.2018.206383