Abstract
Dialysis-related amyloidosis (DRA), which has been widely recognized to be associated with the accumulation of β2-microglobulin (β2-m) in blood, is one of the most common complications in patients receiving long-term dialysis treatment. The most significant side-effect of existing hemodialysis sorbents for the removal of β2-m from blood is the loss of vital proteins due to non-specific adsorptions. Although the traditional antibodies have the capability to specifically remove β2-m from blood, high cost limits their applications in clinics. Single domain antibodies derived from the Camelidae species serve as a superior choice in the preparation of immunoadsorbents due to their small size, high stability, amenability, simplicity of expression in microbes, and high affinity to recognize and interact with β2-m. In this study, we modified the anti-β2-m VHH by the formylglycine-generating enzyme (FGE), and then directly immobilized the aldehyde-modified VHH to the amino-activated beads. Notably, the fabrication is cost- and time-effective, since all the preparation steps were performed in the crude cell extract without rigorous purification. The accordingly prepared immunoadsorbent with VHHs as ligands exhibited the high capacity of β2-m (0.75 mg/mL). In conclusion, the VHH antibodies were successfully used as affinity ligands in the preparation of novel immunoadsorbents by the site-specific immobilization, and effectively adsorbed β2-m from blood, therefore opening a new avenue for efficient hemodialysis.
Highlights
The kidney plays a central role in the removal of metabolic wastes from our bloodstream by making urine
Chronic kidney disease, which involves persistent kidney injury or glomerular filtration rate (GFR) lower than 60 mL/min per 1.73 m2 for 90 days or longer, has been proven to be a primary fast-growing health problem around the world, contributing to the rising of kidney failure, cardiovascular disease (CVD), and premature death [1,2,3]
Β2-Microglobulin (β2-m), a highly conserved globular protein (11.8 kDa), is a major middle-molecular uremic toxin. β2-m is a component of the major histocompatibility complex on almost all nucleated cell membranes, which can detach from the membrane and eventually be catabolized in renal tubules
Summary
The kidney plays a central role in the removal of metabolic wastes from our bloodstream by making urine. Β2-Microglobulin (β2-m), a highly conserved globular protein (11.8 kDa), is a major middle-molecular uremic toxin. Β2-m is a component of the major histocompatibility complex on almost all nucleated cell membranes, which can detach from the membrane and eventually be catabolized in renal tubules. The pathological concentration of β2-m in hemodialysis patients might rise to a level that is 50 times higher than that under normal conditions [4]. Traditional hemodialysis devices fail to eliminate β2-m from blood, and lead to the long-term accumulation of β2-m in serum or systemic organs [5]. The resulting deposits have been identified as dialysis-related amyloidosis (DRA) [6]. Symptoms in patients with DRA [7,8] mainly consist of joint pain, carpal tunnel
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