A novel immunoadsorption device for removing beta2-microglobulin from whole blood.
BACKGROUND
High plasma levels of beta2-microglobulin (beta2m) have been implicated in the formation of the severely destructive and potentially fatal amyloid deposits that are characteristic of dialysis-related amyloidosis (DRA). Conventional renal replacement technologies remove insufficient quantities of beta2m 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 nonspecific approaches also make it difficult to evaluate the role and contribution of middle molecular weight molecules to the pathology of DRA and other morbidities of end-stage renal disease. A high-affinity and biologically specific approach could target a protein, prevent a significant loss of other important molecules, and improve the apparent adsorption rate within an extracorporeal device.


METHODS
Agarose-immobilized murine anti-human beta2m monoclonal antibodies were used in a Vortex Flow Plasmapheretic Reactor (VFPR) to remove donor baseline and controlled amounts of recombinant beta2m from human blood in vitro. The extracorporeal circuit was hemoperfused at 200 mL/min for two hours.


RESULTS
The immunoadsorptive media had a binding site density of 30 microg beta2m per mL of settled gel. The VFPR cleared baseline quantities of donor beta2m below detectable limits of the assay. The experiments with higher initial beta2m concentrations reached an equilibrium concentration within 20 minutes, corresponding to a 92% clearance. No deleterious hemocompatibility issues were observed (complete blood count, total protein, and plasma free hemoglobin).


CONCLUSIONS
The adsorptive kinetics of the VFPR are optimal for the conditions used and support the use of immunoadsorption for the removal of beta2m.
Ameer
G A
GA
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA. gameer@mit.edu
Grovender
E A
EA
Ploegh
H
H
Ting
D
D
Owen
W F
WF
Rupnick
M
M
Langer
R
R
D001781:Blood Component Removal / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D007163:Immunosorbent Techniques / Q000295:instrumentation*; D007700:Kinetics; D010956:Plasmapheresis / Q000295:instrumentation; D011994:Recombinant Proteins / Q000097:blood; D001613:beta 2-Microglobulin / Q000097:blood*
D011994:Recombinant Proteins; D001613:beta 2-Microglobulin