A novel immunoadsorption device for removing beta(2)-microglobulin from whole blood

Background. High plasma levels of beta (2)-microglobulin (beta (2)m) have b een implicated in the formation of the severely destructive and potentially fatal amyloid deposits that are characteristic of dialysis-related amyloid osis (DRA). Conventional renal replacement technologies remove insufficient quantities of beta (2)m to normalize plasma levels. This limitation arises because of nonspecific adsorptive qualities and reliance on size exclusion , which can also remove other middle molecular weight proteins. These nonsp ecific approaches also make it difficult to evaluate the role and contribut ion of middle molecular weight molecules to the pathology of DRA and other morbidities of end-stage renal disease. A high affinity and biologically sp ecific approach could target a protein, prevent a significant loss of other important molecules, and improve the apparent adsorption rate within an ex tracorporeal device. Methods. Agarose-immobilized murine anti-human beta (2)m monoclonal antibod ies were used in a Vortex Flow Plasmapheretic Reactor (VFPR) to remove dono r baseline and controlled amounts of recombinant beta (2)m from human blood in vitro. The extracorporeal circuit was hemoperfused at 200 mL/min for tw o hours. Results. The immunoadsorptive media had a binding site density of 30 mug be ta (2)m per mt of settled gel. The VFPR cleared baseline quantities of dono r beta (2)m below detectable limits of the assay. The experiments with high er initial beta (2)m concentrations reached an equilibrium concentration wi thin 20 minutes, corresponding to a 92% clearance. No deleterious hemocompa tibility issues were observed (complete blood count, total protein, and pla sma free hemoglobin). Conclusions. The adsorptive kinetics of the VFPR are optimal for the condit ions used and support the use of immunoadsorption for the removal of beta ( 2)m.