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Published on: April 16, 2016
A novel immunoadsorption device for removing beta2-microglobulin from whole blood
G A Ameer1, E A Grovender, H Ploegh
1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA. gameer@mit.edu
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.
Insights
This study demonstrates that immunoadsorption using a Vortex Flow Plasmapheretic Reactor effectively removes beta2-microglobulin (beta2m), a key factor in dialysis-related amyloidosis. This specific approach shows promise for improving patient outcomes in end-stage renal disease.
Area of Science:
- Nephrology
- Biomedical Engineering
- Immunology
Background:
- High plasma beta2-microglobulin (beta2m) is linked to dialysis-related amyloidosis (DRA).
- Conventional renal replacement therapies inadequately remove beta2m due to nonspecific mechanisms.
- Nonspecific removal hinders understanding of middle molecule roles in end-stage renal disease (ESRD) pathology.
Purpose of the Study:
- To evaluate the efficacy of a specific immunoadsorption approach for beta2m removal.
- To assess the performance of a Vortex Flow Plasmapheretic Reactor (VFPR) utilizing anti-beta2m antibodies.
- To determine if specific beta2m targeting can prevent loss of other essential proteins.
Main Methods:
- Utilized agarose-immobilized murine anti-human beta2m monoclonal antibodies in a VFPR.
- Hemoperfused human blood in an extracorporeal circuit at 200 mL/min for two hours.
- Tested removal of baseline and controlled recombinant beta2m concentrations.
Main Results:
- Immunoadsorbent media exhibited a binding site density of 30 microg beta2m/mL.
- VFPR cleared baseline beta2m to undetectable levels.
- Achieved 92% beta2m clearance within 20 minutes for higher concentrations.
- No adverse hemocompatibility issues were observed.
Conclusions:
- The VFPR demonstrates optimal adsorptive kinetics for beta2m removal under tested conditions.
- Immunoadsorption is a viable strategy for targeting and reducing beta2m levels.
- This specific approach supports further investigation for managing DRA and ESRD morbidities.
