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Antigen-antibody complexes in hemophilia.

Antigen-antibody complexes have been found by several groups of investigators in patients with hemophilia. The amount of circulating immune complexes (CIC) has varied with the assay method, the largest amount has been found with the Staph binding assay and the smallest with the Raji cell method. We have correlated the level of immune complexes detected by both the Raji cell and the Staph binding assay with clinical disease status: joint disease, positive inhibitor status, and hematuria but not hepatitis. The complexes are formed with different antigens, Factor VIII, the Factor VIII inhibitor, and antibody to the hepatitis B surface antigen for example have been detected in isolated CIC. CIC have not been detected in synovium or vasculature and rarely in the synovial fluid. The effect of the infusion of concentrate on the levels of the immune complexes is variable among patients but consistent within individuals over time. Studies by our group show a rise in CIC in 3 patients and a fall in six following concentrate infusion with return to baseline in 24 hours. In vitro studies of the monomuclear phagocyte system Fc receptor function showed enhanced function in those six patients whose levels decreased post infusion while the three with rise in CIC showed a prolonged clearance and decreased mononuclear phagocyte system function. This effect was not correlated with the amount of infusion or the yearly use of the concentrate. Changes in CIC were not due to infusion of preformed complexes in the Factor VIII concentrate nor to de novo formation of CIC since in vitro incubation of pre-infusion serum with concentrate revealed no change in CIC levels. However, change in reticulo endothelial Fc receptor function correlated with the changes in CIC suggesting a modulation of monocyte function by Factor VIII concentrate infusion. In summary, circulating immune complexes are present in transfused hemophiliacs which may be associated with secondary disease, and regulation of the immune function in these patients.