A novel immunoadsorption device for removing β2-microglobulin from whole blood

Guillermo A. Ameer, Eric A. Grovender, Hidde Ploegh, David Ting, William F. Owen, Maria Rupnick, Robert Langer

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background. High plasma levels of β2-microglobulin (β2m) 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 β2m 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 β2m monoclonal antibodies were used in a Vortex Flow Plasmapheretic Reactor (VFPR) to remove donor baseline and controlled amounts of recombinant β2m 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 μg β2m per mL of settled gel. The VFPR cleared baseline quantities of donor β2m below detectable limits of the assay. The experiments with higher initial β2m 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 β2m.

Original languageEnglish (US)
Pages (from-to)1544-1550
Number of pages7
JournalKidney international
Volume59
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Dialysis-related amyloidosis
  • Extracorporeal immunoadsorption
  • Hemocompatibility
  • Middle molecular weight molecules
  • Renal replacement therapy
  • Vortex flow

ASJC Scopus subject areas

  • Nephrology

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