Distribution of Th1- and Th2-induced Anti-factor VIII IgG Subclasses in Congenital and Acquired Hemophilia Patients

Mark T. Reding; Sijin Lei; Howard Lei; Daid Green; Joan Gill; Bianca M. Conti-Fine

doi:10.1055/s-0037-1613257

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 88(04): 568-575
DOI: 10.1055/s-0037-1613257

Review Article

Schattauer GmbH

Distribution of Th1- and Th2-induced Anti-factor VIII IgG Subclasses in Congenital and Acquired Hemophilia Patients

Authors

Mark T. Reding

¹Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN

²Department of Medicine, University of Minnesota, Minneapolis-St. Paul, MN
Sijin Lei

¹Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN
Howard Lei

¹Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN
Daid Green

³Northwestern University Medical School, Chicago, IL
Joan Gill

⁴Blood Center of SE Wisconsin Comprehensive Center for Bleeding Disorders, Milwaukee, WI, USA
Bianca M. Conti-Fine

¹Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN

Abstract

Summary

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.

Keywords

Th1 cells - Th2 cells - factor VIII - antibodies - hemophilia A - acquired hemophilia

Volltext

Referenzen

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