BACKGROUND: Dialysis-related amyloidosis (DRA) is a devastating and costly condition that affects patients with end stage kidney disease. A key feature of DRA is the formation of amyloid fibrils, consisting primarily of beta2-microglobulin. Except for kidney transplantation, conventional kidney replacement therapies, which are based on nonspecific mechanisms, do not adequately address beta2-microglobulin removal. An antihuman beta2-microglobulin single-chain variable region antibody fragment (scFv) was developed to confer specificity to beta2-microglobulin removal during hemodialysis. METHODS: The scFv was immobilized onto agarose and characterized for beta2m binding capacity, thermal stability at 37 degrees C, regeneration capacity, storage conditions, and sterility. RESULTS: The beta2-microglobulin binding capacity was 1.3 mg/ml scFv gel. The immunoadsorbent is thermally stable, can be regenerated, stored short-term in 20% ethanol, lyophilized for long-term storage, and withstand process conditions similar to that of a patient's hemodialysis therapy. CONCLUSIONS: The results support further investigation of immobilized scFvs as a novel tool to remove beta2-microglobulin from blood.
BACKGROUND: Dialysis-related amyloidosis (DRA) is a devastating and costly condition that affects patients with end stage kidney disease. A key feature of DRA is the formation of amyloid fibrils, consisting primarily of beta2-microglobulin. Except for kidney transplantation, conventional kidney replacement therapies, which are based on nonspecific mechanisms, do not adequately address beta2-microglobulin removal. An antihuman beta2-microglobulin single-chain variable region antibody fragment (scFv) was developed to confer specificity to beta2-microglobulin removal during hemodialysis. METHODS: The scFv was immobilized onto agarose and characterized for beta2m binding capacity, thermal stability at 37 degrees C, regeneration capacity, storage conditions, and sterility. RESULTS: The beta2-microglobulin binding capacity was 1.3 mg/ml scFv gel. The immunoadsorbent is thermally stable, can be regenerated, stored short-term in 20% ethanol, lyophilized for long-term storage, and withstand process conditions similar to that of a patient's hemodialysis therapy. CONCLUSIONS: The results support further investigation of immobilized scFvs as a novel tool to remove beta2-microglobulin from blood.
Authors: Yangrong Zhang; Karen A Lapidos; Anca Gal-Moscovici; Stuart M Sprague; Guillermo A Ameer Journal: Artif Organs Date: 2013-11-11 Impact factor: 3.094