title: Higher frequency of CD4(+)CD25(high) Treg cells in hemophilia patients with factor VIII inhibitor.
abstract: 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.
authors.affiliation: Anhui Provincial Hospital Affiliated, Anhui Medical University, Hefei, Anhui Province, China dingkaiy@126.com.
authors.forename: K Y
authors.initials: KY
authors.lastname: Ding
authors.affiliation: Anhui Provincial Hospital Affiliated, Anhui Medical University, Hefei, Anhui Province, China.
authors.forename: W C
authors.initials: WC
authors.lastname: Ji
authors.affiliation: Anhui Provincial Hospital Affiliated, Anhui Medical University, Hefei, Anhui Province, China.
authors.forename: J S
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Anhui Provincial Hospital Affiliated, Anhui Medical University, Hefei, Anhui Province, China.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.affiliation: Anhui Provincial Hospital Affiliated, Anhui Medical University, Hefei, Anhui Province, China.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Sheng
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005169:Factor VIII / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000276:immunology; D005434:Flow Cytometry; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C078147:F8 protein, human; D005169:Factor VIII