Immunoresponsiveness in hemophilia: lymphocyte- and phagocyte-mediated functions

Several deficits of immune response have been reported in hemophiliacs. In order to evaluate the overall immune function in this disease, we have investigated peripheral blood mononuclear cells (PBMC) surface phenotype, lymphokine production, B cell responsiveness, monocyte- and polymorphonuclear (PMN) cell-mediated responses in a group of 25 A or B hemophiliac patients. They were treated with concentrates (greater than 30,000 U/year) for at least 8 years, and ten of them were positive for human immunodeficiency virus (HIV) infection. With particular reference to lymphocyte surface markers, a low CD4+/CD8+ ratio and an increased frequency of CD25+ and surface immunoglobulin (sIg) positive lymphocytes were noted in HIV+ subjects. By contrast, CD3+ and CD4+ cell frequency was decreased in HIV- patients, whereas in the same individuals CD11+ and sIg+ cell percentage was augmented. Regardless of HIV infection, a quite variable degree of B-cell response was seen in hemophiliacs with either a T-independent or a T-dependent polyclonal B cell activator. PMN chemotaxis, phagocytosis, and killing were significantly diminished, whereas similar monocyte functions were basically unaffected. Finally, hemophiliacs were characterized by a profound impairment of leukocyte inhibiting factor (LIF) and lymphocyte-derived chemotactic factor (LDCF) production. Our findings clearly indicate an impairment of immune function in hemophiliacs regardless of HIV infection.