Immunoadsorption model for a novel fluidized‐bed blood detoxification device

Grovender, Eric A.; Cooney, Charles L.; Langer, Robert

doi:10.1002/aic.690481025

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…The K D value between wild-type b2m and BBM.1 is determined to be 1.0 nM, which is consistent with the previously reported values based on the immunoadsorption analysis using agarose-immobilized BBM.1 and free form b2m (K D ¼ 8.5 AE 8.5 nM) (Grovender et al, 2002) and based on the Scatchard plot analysis using BBM.1 and HLA-I associated b2m (K D < 10 nM) (Parham et al, 1983). The K D values between the mutant b2m and BBM.1 are listed in Table 1.…”

Section: Evaluation Of the Representative Complex Models By Computatimentioning

confidence: 48%

Structural modeling and biochemical studies reveal insights into the molecular basis of the recognition of β‐2‐microglobulin by antibody BBM.1

Peng

et al. 2009

J of Molecular Recognition

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Human beta-2-microglobulin (beta2m) is the light chain of human leucocyte antigen-I (HLA-I). It can disassociate from HLA-I and accumulate to cause serious dialysis-related amyloidosis (DRA) in long-term hemodialysis patients. Monoclonal antibody (mAb) BBM.1 can recognize both free-form and HLA-I associated beta2m. It can be used for specific elimination of beta2m from serum and can induce apoptosis of several types of tumor cells, and thus has great therapeutic potential. In this study, we constructed structural models of the BBM.1 Fv (fragment of the variable domain) and the BBM.1 Fv-beta2m complex, followed by biochemical evaluation. Analysis of the optimal complex model reveals that the previously identified immunodominant residues Glu(44) and Arg(45) of beta2m have direct interactions with BBM.1, while Asp(38) exerts its function mainly via stabilization of Arg(45). In addition, Arg(81) of beta2m is a newly identified immunodominant residue to have direct interaction with BBM.1. Further modeling study shows no steric conflict between the antibody and the HLA-I heavy chain. These results provide insights into the molecular basis of the recognition of beta2m by BBM.1 and explain why BBM.1 can bind both free-form and HLA-1 associated beta2m. This information could be exploited in the engineering and improvement of BBM.1 and the development of other beta2m-targeting mAbs for therapeutic purposes.

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Section: Evaluation Of the Representative Complex Models By Computatimentioning

confidence: 48%

Structural modeling and biochemical studies reveal insights into the molecular basis of the recognition of β‐2‐microglobulin by antibody BBM.1

Peng

et al. 2009

J of Molecular Recognition

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“…The binding capacity for glycolaldehyde‐derived AGE‐bovine serum albumin (BSA) (Fitzgerald Industries International, Acton, MA, USA) and the equilibrium dissociation constant K D between AGE‐BSA and the bioadsorbent were measured as described previously . Thermal stability of the bioadsorbent was assessed by incubating for 4 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

A Receptor‐Based Bioadsorbent to Target Advanced Glycation End Products in Chronic Kidney Disease

et al. 2013

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The accumulation of advanced glycation end products (AGEs) has been reported to be a major contributor to chronic systemic inflammation. AGEs are not efficiently removed by hemodialysis or the kidney of a chronic kidney disease (CKD) patient. The goal of this study was to develop a receptor for AGEs (RAGE)-based bioadsorbent device that was capable of removing endogenous AGEs from human blood. The extracellular domain of RAGE was immobilized onto agarose beads to generate the bioadsorbent. The efficacy of AGE removal from saline, serum, and whole blood; biological effects of AGE reduction; and hemocompatibility and stability of the bioadsorbent were investigated. The bioadsorbent bound AGE-modified bovine serum albumin (AGE-BSA) with a binding capacity of 0.73 ± 0.07 mg AGE-BSA/ml bioadsorbent. The bioadsorbent significantly reduced the concentration of total AGEs in serum isolated from end stage kidney disease (ESKD) patients by 57%. AGE removal resulted in a significant reduction of vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells and abolishment of osteoclast formation in osteoclast progenitor cells. A hollow fiber device loaded with bioadsorbent reduced endogenous AGEs from recirculated blood to 36% of baseline levels with no significant changes in total protein and albumin concentration. The bioadsorbent maintained AGE-specific binding capacity after freeze-drying and storage for 1 year. This approach provides the foundation for further development of sRAGE-based extracorporeal therapies to selectively deplete serum AGEs from human blood and decrease inflammation in patients with diabetes and/or CKD.

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Nanobody-Based high-performance immunosorbent for selective beta 2-microglobulin purification from blood

Huang

Ren

et al. 2020

Acta Biomaterialia

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Immunoadsorption model for a novel fluidized‐bed blood detoxification device

Cited by 4 publications

References 19 publications

Structural modeling and biochemical studies reveal insights into the molecular basis of the recognition of β‐2‐microglobulin by antibody BBM.1

Structural modeling and biochemical studies reveal insights into the molecular basis of the recognition of β‐2‐microglobulin by antibody BBM.1

A Receptor‐Based Bioadsorbent to Target Advanced Glycation End Products in Chronic Kidney Disease

Nanobody-Based high-performance immunosorbent for selective beta 2-microglobulin purification from blood

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