Induction of tolerance to factor VIII in a child with a high-titer inhibitor: In vitro and in vivo observations

Gomperts, Edward D.; Jordan, Stanley C.; Church, Joseph A.; Sakai, Rina; Lemire, Jacques

doi:10.1016/s0022-3476(84)80592-2

Cited by 21 publications

(10 citation statements)

References 16 publications

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“…In addition to the evaluation of FVIII inhibitory activity, mAbs were characterised using a combination of methods, as reported previously [Gilles, J.G., et al, submitted]: (1) binding to ni trocellulose sheets blotted with native or thrombin-digested FVIII; (2) binding to polystyrene plates coated with native FVIII or purified heavy or light chain; (3) binding to FVIII insolubilised on vWF-or phosphatidylserine-coated plates; (4) cross-inhibition ELISA with mAbs Cag 117, Cag 69, CagA and Cag9 of the CLB series and of known specificity (obtained by courtesy of the Netherlands Red Cross) [15,16], and (5) immunoprécipitation with soluble recombi nant fragments of the A2, Cl and C2 domains of FVIII (carried out by Dr. Scandella, Rockville) as described [17]. Five antibodies from the ESH mAb series that did not cross-react with mAbs of our own pro duction were also used in the assay systems.…”

Section: Preparation and Use Of Rabbit Antiseramentioning

confidence: 99%

“…Up to 30% of patients treated by FVIII infusions produce antibodies that neutralise the pro-coagulant activity of the molecule, which restricts their treatment to alternative strat egies or desensitisation trials with high doses of FVIII [1][2][3]. The reasons why a haemophilia A patient develops such an immune response are not entirely elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Gilles¹,

Giambattista²,

Laub³

et al. 1997

Vox Sanguinis

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Background and objectives: Alterations of factor Vili (FVIII) during preparation procedures can potentially affect its immunogenicity. One method evaluating such alterations could be by determining the reactivity of FVIII with specific antibodies. Materials and methods: Since heat treatment is currently used to reduce the risk of viral transmission, we evaluated the immunoreactivity of plasma-derived FVIII before and after heating at different temperatures and for different periods. Freeze-dried FVIII was used for these experiments as part of the validation procedure of a novel FVIII preparation. Results: Ideating FVIII for up to 72 hat 80 °C does not alter its reactivity with specific rabbit antibodies or mouse monoclonal antibodies, although some loss of FVIII activity occurred after 72 h. After heating for 2 h at 100°C, a procedure that reduced FVIII activity by about 50%, there were still no significant effects on FVIII reactivity with monoclonal antibodies. Conclusions: Freeze-dried preparations of plasma-derived FVIII seem to be resistant to heat-induced structural dénaturation.

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Section: Preparation and Use Of Rabbit Antiseramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Gilles¹,

Giambattista²,

Laub³

et al. 1997

Vox Sanguinis

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“…Immunisation against factor VIII (FVIII) is presently one of the major problems faced by haemophilia A patients. Up to 30% of patients treated by FVIII infusions produce antibodies that neutralise the pro-coagulant activity of the molecule, which restricts their treatment to alternative strategies or desensitisation trials with high doses of FVIII [1][2][3]. The reasons why a haemophilia A patient develops such an immune response are not entirely elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…mAb Specificity. In addition to the evaluation of FVIII inhibitory activity, mAbs were characterised using a combination of methods, as reported previously [Gilles, J.G., et al, submitted]: (1) binding to nitrocellulose sheets blotted with native or thrombin-digested FVIII; (2) binding to polystyrene plates coated with native FVIII or purified heavy or light chain; (3) binding to FVIII insolubilised on vWF-or phosphatidylserine-coated plates; (4) cross-inhibition ELISA with mAbs Cag 117, Cag 69, Cag A and Cag 9 of the CLB series and of known specificity (obtained by courtesy of the Netherlands Red Cross) [15,16], and (5) immunoprecipitation with soluble recombinant fragments of the A2, C1 and C2 domains of FVIII (carried out by Dr. Scandella, Rockville) as described [17]. Five antibodies from the ESH mAb series that did not cross-react with mAbs of our own production were also used in the assay systems.…”

mentioning

confidence: 99%

Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Gilles

Giambattista²,

Laub³

et al. 1997

Vox Sanguinis

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“…As a result, replacement therapy using factor VIII preparations becomes ineffective as a means of correcting bleeding episodes. A variety of methods have been utilized to treat bleeding episodes in inhibitor patients, including immunosuppression (3), antibody depletion through plasmapheresis (4), high-dose factor VIII therapy leading to immune tolerance (5)(6)(7), and repeated treatment with factor VIII combined with immunosuppression (8). Prothrombin complex concentrates have proven to be partially effective (9-1 1) but their use is controversial owing to uncertainty with regard to the putative factors responsible (12)(13)(14), thrombogenicity (15)(16)(17), and the risk of viral infections.…”

Section: Introductionmentioning

confidence: 99%

Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model.

O'Brien¹,

Giles²,

Tate³

et al. 1988

J. Clin. Invest.

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The bleeding disorder of hemophilia A currently treated by replacement therapy of the missing coagulation factor, factor VIII, is frequently complicated by the development of neutralizing antibodies. The therapeutic potential of attenuated forms of the lipid-associated glycoprotein tissue factor, a known initiator of coagulation, was investigated as a factor VIII-bypassing activity. The protein moiety of tissue factor (Apo-TF) was partially purified and exhibited minimal procoagulant activity before relipidation in vitro. In pilot studies, Apo-TF injection into rabbits previously anticoagulated with an antibody to factor VIII was found to have a procoagulant effect. The efficacy of the material was further demonstrated when injection of Apo-TF in hemophilic dogs resulted in a normalization of the cuticle bleeding time. Little or no change in the blood parameters associated with disseminated intravascular coagulation was observed at lower doses, although mild to moderate effects were seen at higher doses. These data suggest a novel role for Apo-TF preparations as a potential therapeutic agent for hemophiliacs with antibodies to factor VIII once the potential thrombogenicity of such materials is evaluated.

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Induction of tolerance to factor VIII in a child with a high-titer inhibitor: In vitro and in vivo observations

Cited by 21 publications

References 16 publications

Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model.

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