Specific antibodies enhance Sephadex-induced activation of the alternative complement pathway in human serum

Sephadex beads, which resemble cellulose in their basic chemical structure, were used to study the molecular mechanisms by which cellulosic dialysis membranes activate the alternative complement pathway in normal human serum. Sera from different individuals were found to vary in the extent of activation which occurred following incubation with a fixed amount (surface area) of polymer. Preadsorption of serum with an excess of Sephadex at 2 degrees C resulted in loss of activation when the absorbed serum was interacted with fresh Sephadex beads. Acid eluted proteins from absorbed Sephadex restored the capacity of preadsorbed serum to activate complement in the presence of fresh Sephadex. Adsorption of the immunoglobulin G (IgG) fraction and of F(ab')2 fragments from IgG prepared from the plasma of a normal individual with Sephadex, resulted in the specific binding of some IgG and F(ab'2) molecules to the particles. IgG and F(ab')2 coated beads activated complement in Sephadex-adsorbed serum. Thus, specific anti-dextran IgG antibodies trigger activation of the alternative complement pathway by Sephadex in human serum. The effect is independent of the Fc region of IgG. These results suggest that specific antibodies could be important in determining complement activation in vivo in patients undergoing haemodialysis with cellulosic membranes.