Inhibitor antibody development and T cell response to human factor VIII in murine hemophilia A

Jiahua Qian, Marina Borovok, Lei Bi, Haig H. Kazazian, Leon W. Hoyer

Research output: Contribution to journalArticlepeer-review

Abstract

In order to understand better the mechanism of inhibitor formation in hemophilia A patients, we have characterized the immune response to human factor VIII in a murine model of hemophilia A. Mice with severe factor VIII deficiency caused by targeted gene disruptions in exons 16 and 17 were injected intravenously with human factor VIII. Antifactor VIII was absent or was detected at only very low levels in hemophilic mice of both strains after a single injection of 0.2 μg factor VIII, but it was present in most mice after a second exposure. Subsequent exposures led to high titer anti-factor VIII antibodies in both ELISA and inhibitor assays. A human factor VIII-specific T cell proliferative response was detected with spleen cells obtained three days after a single injection with human factor VIII, before mice had detectable anti-factor VIII antibodies. Subsequent exposures to factor VIII were followed by an increased T cell proliferative response. These studies indicate that murine hemophilia A is a good model for the study of the immune response to human factor VIII, especially the role of the T cell in the early steps in inhibitor antibody formation.

Original languageEnglish (US)
Pages (from-to)240-244
Number of pages5
JournalThrombosis and Haemostasis
Volume81
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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