title: Soluble interleukin 2 receptor and soluble CD8 levels in previously treated human immunodeficiency virus-negative hemophiliacs multiply transfused with a monoclonal antibody-purified factor VIII concentrate.
abstract: BACKGROUND
  Serum levels of the soluble interleukin 2 receptor (sIL-2R) and soluble CD8 (sCD8) may be used as markers of T-cell activation. The course of serum levels of sIL-2R and sCD8 in hemophiliacs who were treated first with an intermediate-purity factor VIII concentrate and then with a monoclonal antibody (MoAb)-purified factor VIII concentrate are reported.
  
  
  METHODS
  Serum samples taken before the administration of the MoAb-purified concentrate and after 2 and 5 years of its administration to 20 human immunodeficiency virus-negative patients with hemophilia A were analyzed. Eighteen healthy age-matched men were used as controls.
  
  
  RESULTS
  The sIL-2R and sCD8 levels were higher in patients treated with intermediate-purity concentrates than in controls (p = 0.006 and p = 0.0005, respectively). The sIL-2R levels showed a decrease after 5 years of treatment with the MoAb-purified concentrate (p = 0.018 for the difference between 2 and 5 years), to levels that were not significantly different from those in controls. Although sCD8 levels tended to decrease at 5 years (p = 0.09, for the difference between 2 and 5 years), they remained higher than those in controls (p = 0.0005 and p = 0.0016 at 2 and 5 years, respectively). The ratio of sCD8 and sIL-2R tended to increase between 2 and 5 years (p = 0.07). The sIL-2R and sCD8 levels were not related to the numbers of T-lymphocytes and HLA-DR-positive T-lymphocytes in peripheral blood. Nor was a relation demonstrated between sIL-2R levels and CD4-positive cell numbers or between sCD8 levels and CD8-positive cell numbers. Although a relation with chronic hepatitis C cannot be excluded, it seems more likely that changes in sIL-2R levels are due to the use of the MoAb-purified concentrate.
  
  
  CONCLUSIONS
  Elevated levels of sIL-2R and sCD8 were found in multiply transfused human immunodeficiency virus-negative hemophiliacs. After treatment was changed to the use of a MoAb-purified concentrate. sIL-2R levels decreased. These findings suggest a change in immune stimulation that is remarkable, because signs of activation in the effector phase seem to have continued despite normalization in the proliferative phase.
authors.affiliation: Division of Haematology, University Hospital, Groningen, The Netherlands.
authors.forename: W M
authors.initials: WM
authors.lastname: Smid
authors.forename: A
authors.initials: A
authors.lastname: Martens
authors.forename: J
authors.initials: J
authors.lastname: van der Meer
authors.forename: C S
authors.initials: CS
authors.lastname: Hegge-Paping
authors.forename: M R
authors.initials: MR
authors.lastname: Halie
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001803:Blood Transfusion; D016827:CD8 Antigens / Q000097:blood*; D005169:Factor VIII / Q000008:administration & dosage* / Q000276:immunology; D018023:HIV Seronegativity / Q000502:physiology*; D006684:HLA-DR Antigens / Q000032:analysis; D006467:Hemophilia A / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D018655:Lymphocyte Count; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2; D005169:Factor VIII