Higher frequency of CD4(+)CD25(high) Treg cells in hemophilia patients with factor VIII inhibitor

The production of factor VIII inhibitor antibodies remains the most costly and serious complication in replacement therapy of hemophilia A. We investigated the clinical significance of CD4(+)CD25(high) T regulatory (Treg) cells in hemophilia patients. Our trial included 6 severe hemophilia A patients with factor VIII inhibitors, 6 hemophilia patients without inhibition of factor VIII, and 6 healthy persons (controls). Plasma factor VIII: c was measured by clotting assay. Peripheral blood samples were examined using mutiparameter flow cytometry with fluorescent-labeled monoclonal antibodies. Plasma levels of IFN-γ, IL-2, IL-10, and TGF-β were measured by ELISA. The frequency of CD4(+)CD25(high) Treg cells in CD4(+) cells was 1.07 ± 0.38% in inhibitor patients and 0.57 ± 0.14% in non-inhibitor patients. The proportion of Treg cells in healthy controls was similar to that of the non-inhibitor patients. However, there were significant differences between the inhibitor and non-inhibitor patients in levels of IFN-γ, IL-2, IL-10, and TGF-β. We conclude that the proportions of Treg cells and the concentrations of T cell cytokines in inhibitor patients are higher than those in non-inhibitor patients. The increased number of Treg cells and increased T-cell cytokines may be related to the development and efficiency of the factor VIII inhibitor.