Toleranzinduktion gegen humanen Faktor VIII in Mäusen — Untersuchungen zur Toleranzaufhebung durch denaturierten Faktor VIII

Reipert, Birgit M.; Ahmad, Rafi; Olas, Katja; Gritsch, Herbert; Turecek, Peter L.; Schwarz, Hans‐Peter

doi:10.1007/978-3-642-59633-9_21

Cited by 2 publications

(2 citation statements)

References 5 publications

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“…Total anti-FVIII antibody titers were measured by ELISA as described previously (21). Briefly, recombinant FVIII was immobilized to PolySorp multiwell plates (Nunc, Roskilde, Denmark).…”

Section: Detection Of Total Anti-fviii Antibodiesmentioning

confidence: 99%

Blockade of CD40/CD40 Ligand Interactions Prevents Induction of Factor VIII Inhibitors in Hemophilic Mice but Does not Induce Lasting Immune Tolerance

Reipert

Sasgary²,

Ahmad³

et al. 2001

Thromb Haemost

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SummaryPatients with severe hemophilia A frequently develop neutralizing anti-factor VIII antibodies after replacement therapy with factor VIII (FVIII). In a search for new strategies to induce immune tolerance against FVIII in these patients, we used a murine model of hemophilia A to investigate the importance of CD40/CD40 ligand (CD40L) interactions for the initiation of the anti-FVIII immune response. We focused our attention in particular on the induction of neutralizing anti-FVIII antibodies and the Th1/Th2 polarization of FVIII-specific T cells. The development of anti-FVIII antibodies was analyzed by ELISA systems (detection of total anti-FVIII antibodies) and Bethesda assays (determination of neutralizing anti-FVIII antibodies). Factor VIII-specific T cells were characterized by multiparameter flow cytometry and cytokine ELISAs for the detection of cytokine production in splenic CD4+ T cells after in vitro restimulation with FVIII. Hemophilic mice received four doses of FVIII and anti-CD40L antibody MR1 (24 h before FVIII). Subsequently mice received four doses of FVIII only. The induction of neutralizing anti-FVIII antibodies in hemophilic mice after treatment with human FVIII could be prevented completely by a blockade of CD40/CD40L interactions using MR1. Furthermore, FVIII-specific T-cell responses that included both Th1 and Th2 cells were suppressed when mice were treated with FVIII and MR1. The initial blockade of CD40/CD40L interactions was, however, not sufficient to induce a lasting immune tolerance against FVIII. The immune suppression was abolished and both neutralizing anti-FVIII antibodies and FVIII-specific T cells developed when treatment with FVIII was continued after the omission of MR1. In addition, there were no alterations in the Th1/Th2 polarization induced by the initial blockade of CD40/CD40L interactions.

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“…Total anti-FVIII antibody titers were measured by ELISA as described previously (21). Briefly, recombinant FVIII was immobilized to PolySorp multiwell plates (Nunc, Roskilde, Denmark).…”

Section: Detection Of Total Anti-fviii Antibodiesmentioning

confidence: 99%

Blockade of CD40/CD40 Ligand Interactions Prevents Induction of Factor VIII Inhibitors in Hemophilic Mice but Does not Induce Lasting Immune Tolerance

Reipert

Sasgary²,

Ahmad³

et al. 2001

Thromb Haemost

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show abstract

“…Total anti-factor VIII antibody titers were determined by ELISA as previously described (11). Briefly, rFVIII was immobilized to the solid phase of PolySorp multiwell plates (Nunc, Roskilde, Denmark).…”

Section: Detection Of Total Anti-factor VIII Antibodiesmentioning

confidence: 99%

Characterization of Antibodies Induced by Human Factor VIII in a Murine Knockout Model of Hemophilia A

Reipert¹,

Ahmad²,

Turecek³

et al. 2000

Thromb Haemost

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SummaryTo investigate the usefulness of factor VIII (FVIII) knockout mice as an animal model of hemophilia A, we characterized the antibody response in FVIII knockout mice to recombinant human FVIII, administered intravenously or subcutaneously with or without adjuvant, and compared results to those in normal mice. Anti-factor VIII antibodies were detected after both intravenous and subcutaneous administration, with the highest titers after subcutaneous administration plus adjuvant. Depending on the administration strategy, knockout mice formed antibodies more rapidly and developed higher titers of inhibitory antibodies (Bethesda) than normal mice, suggesting differences in epitope specificity. Blotting thrombin cleavage products separated by gel electrophoresis showed that both strains developed antibodies against the nonfunctional B domain as well as against functional domains of factor VIII. The antibodies were mainly of the IgG1 subclass and resembled type I antibodies in hemophilia A.

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Toleranzinduktion gegen humanen Faktor VIII in Mäusen — Untersuchungen zur Toleranzaufhebung durch denaturierten Faktor VIII

Cited by 2 publications

References 5 publications

Blockade of CD40/CD40 Ligand Interactions Prevents Induction of Factor VIII Inhibitors in Hemophilic Mice but Does not Induce Lasting Immune Tolerance

Blockade of CD40/CD40 Ligand Interactions Prevents Induction of Factor VIII Inhibitors in Hemophilic Mice but Does not Induce Lasting Immune Tolerance

Characterization of Antibodies Induced by Human Factor VIII in a Murine Knockout Model of Hemophilia A

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