INTERFERON-GAMMA SECRETION DEFECTS IN HEMOPHILIA-A PATIENTS RECEIVINGHIGHLY PURIFIED PLASMA-DERIVED OR RECOMBINANT FACTOR-VIII

The outcome of developing immune responses is influenced by interactio ns among a large and complex network of secreted cytokines. T-cell sec retion 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, I L-5 and IL-6 contributes to development of humoral immunity. Humoral i mmunity to factor VIII (FVIII) develops in approximately 25% of severe haemophilia patients. The aim of our research was to understand the u nderlying immune response to FVIII in patients with FVIII inhibitors, We report a defect in IFN-gamma secretion by peripheral blood mononucl ear cells (PBMC) derived from haemophilia A patients, which was accomp anied by a low level of mitogen-induced proliferation and a significan t decrease in the percentage of natural killer (NK) cells. All of the observed defects were found in haemophilia A patients, both with and w ithout FVIII inhibitors, who were free of viral infection and had been treated predominantly or exclusively with monoclonal antibody-purifie d or recombinant FVIII.