Interferon-gamma secretion defects in haemophilia A patients receiving highly purified plasma-derived or recombinant factor VIII.
The outcome of developing immune responses is influenced by interactions among a large and complex network of secreted cytokines. T-cell secretion of interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and TNF-beta, or lymphotoxin contributes to the development of cell-mediated immunity, whereas secretion of interleukin (IL)-4, IL-5 and IL-6 contributes to development of humoral immunity. Humoral immunity to factor VIII (FVIII) develops in approximately 25% of severe haemophilia A patients. The aim of our research was to understand the underlying immune response to FVIII in patients with FVIII inhibitors. We report a defect in IFN-gamma secretion by peripheral blood mononuclear cells (PBMC) derived from haemophilia A patients, which was accompanied by a low level of mitogen-induced proliferation and a significant decrease in the percentage of natural killer (NK) cells. All of the observed defects were found in haemophilia A patients, both with and without FVIII inhibitors, who were free of viral infection and had been treated predominantly or exclusively with monoclonal antibody-purified or recombinant FVIII.
Newton-Nash
D K
DK
Blood Center of Southeastern Wisconsin, Milwaukee 53201-2178, USA.
Tollerud
D
D
Guevarra
L
L
Gill
J C
JC
D002675:Child, Preschool; D005169:Factor VIII / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006467:Hemophilia A / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005169:Factor VIII