Distribution of Th1- and Th2-induced anti-factor VIII IgG subclasses in congenital and acquired hemophilia patients

Mark T. Reding*, Sijin Lei, Howard Lei, David Green, Joan Gill, Bianca M. Conti-Fine

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Development of antibodies (Ab) that inhibit the procoagulant function of factor VIII (fVIII) seriously complicates the treatment of hemophilia A patients. It also causes acquired hemophilia, a rare yet serious autoimmune disease. The design of effective fVIII-specific tolerizing procedures will require elucidation of the role of the different CD4+ T cell subsets that drive inhibitor synthesis. To examine the contribution of Th1 and Th2 cells in the anti-fVIII Ab response, we measured the concentration of Th1- and Th2-driven anti-fVIII IgG subclasses in 17 patients with severe hemophilia A and 18 patients with acquired hemophilia. We found that both congenital and acquired hemophilia patients had similar and comparable proportions of Th1- and Th2-induced anti-fVIII Ab, suggesting a more important role of Th1 cells in the immune response to fVIII than previously appreciated. The distribution of anti-fVIII IgG subclasses was stable for periods of up to six months. More intense anti-fVIII Ab responses and higher inhibitor titers correlated with a predominance of Th2-driven subclasses. In contrast, Th1-driven anti-fVIII Ab were predominant in patients who had low anti-fVIII Ab concentrations, even when this was the result of successful immune tolerance or immunosuppressive therapy, which had caused drastic reduction or disappearance of inhibitors. Thus, synthesis of Th2-driven inhibitors occurs when the anti-fVIII Ab response is intense, while Th1 cells may be involved in the long-term maintenance of anti-fVIII Ab synthesis.

Original languageEnglish (US)
Pages (from-to)568-575
Number of pages8
JournalThrombosis and Haemostasis
Volume88
Issue number4
DOIs
StatePublished - Oct 1 2002

Keywords

  • Acquired hemophilia
  • Antibodies
  • Factor VIII
  • Hemophilia A
  • Th1 cells
  • Th2 cells

ASJC Scopus subject areas

  • Hematology

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