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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

Mark T. Reding
1   Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN
2   Department of Medicine, University of Minnesota, Minneapolis-St. Paul, MN
,
Sijin Lei
1   Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN
,
Howard Lei
1   Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN
,
Daid Green
3   Northwestern University Medical School, Chicago, IL
,
Joan Gill
4   Blood Center of SE Wisconsin Comprehensive Center for Bleeding Disorders, Milwaukee, WI, USA
,
Bianca M. Conti-Fine
1   Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis-St. Paul, MN
› Author AffiliationsSupported by NHLBI grant HL61922 (to B.M.C.-F.). M.T.R. is the recipient of a Judith Graham Pool Postdoctoral Research Fellowship from the National Hemophilia Foundation tolerance procedures, such as those that might be useful for the treatment of fVIII inhibitors in hemophilia.
Further Information

Publication History

Received 09 July 2001

Accepted after resubmission 06 May 2002

Publication Date:
09 December 2017 (online)

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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
 

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