Antibody concentrations to Aβ1–42 monomer and soluble oligomers in untreated and antibody–antigen-dissociated intravenous immunoglobulin preparations

Klaver, Andrea C.; Finke, John M.; Digambaranath, Jyothi L.; Balasubramaniam, M.; Loeffler, David A.

doi:10.1016/j.intimp.2009.10.005

Cited by 47 publications

(62 citation statements)

References 38 publications

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“…The other antibody drug is IVIG (intravenous immunoglobulin), a natural polyclonal IgG antibody mixture purified from pooled human blood [6]. Both antibody products have been shown to bind soluble oligomeric forms of Ab (OAb) [7][8][9][10]. Thus, it may be possible to increase these clinical effects with an optimal modification of the binding thermodynamics and kinetics with OAb.…”

Section: Introductionmentioning

confidence: 99%

“…AD antibody drugs may yield meaningful clinical results if they can mimic natural anti-Ab antibody properties [8,10,11]. Currently, this hypothesis is difficult to address because the affinity and kinetics of natural antibody binding to linear epitopes of monomeric Ab (MAb) and conformational neo-epitopes of soluble oligomers (OAb) or insoluble fibrils (FAb) are not well characterized.…”

Section: Introductionmentioning

confidence: 99%

“…Enzyme-linked immuosorbent assay (ELISA) methodologies are common approaches used to measure Ab + IgG concentrations [8,9,11,13]. However, thermodynamic K D measurements by natural Ab + IgG by ELISA are challenging for a number of reasons.…”

Section: Introductionmentioning

confidence: 99%

“…standard ELISA is performed under conditions of high ligand immobilization where minimal IgG analyte remains equilibrated in solution. Second, natural human IgG preparations contain very high background signal due to polyvalent antibodies [8,14]. Third, MAb peptides have been shown to adopt OAb and FAb conformations when immobilized on ELISA plates and affinity column matrices [11].…”

Section: Introductionmentioning

confidence: 99%

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Kinetic analysis of IgG antibodies to beta-amyloid oligomers with surface plasmon resonance

Crisostomo

Dang

Digambaranath

et al. 2015

Analytical Biochemistry

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Surface plasmon resonance was used to investigate the kinetics, affinity, and specificity of binding between anti-Aβ (beta-amyloid) IgG antibodies and oligomeric Aβ. Two factors were needed to accurately characterize the IgG binding kinetics. First, a bivalent model was necessary to properly fit the kinetic association and dissociation sensograms. Second, a high concentration of IgG was necessary to overcome a significant mass transport limitation that existed regardless of oligomer density on the sensor surface. Using high IgG concentrations and bivalent fits, consistent kinetic parameters were found at varying sensor surface ligand densities. A comparison of binding specificity, affinity, and kinetic flux between monoclonal and natural human anti-Aβ IgG antibodies revealed the following findings. First, monoclonal antibodies 6E10 and 4G8 single-site binding affinity is similar between Aβ oligomers and monomers. Second, natural human anti-Aβ IgG binding readily binds Aβ oligomers but does not bind monomers. Third, natural human anti-Aβ IgG binds Aβ oligomers with a higher affinity and kinetic flux than 6E10 and 4G8. Both the current analytical methodology and antibody binding profiles are important for advances in antibody drug development and kinetic biomarker applications for Alzheimer's disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Kinetic analysis of IgG antibodies to beta-amyloid oligomers with surface plasmon resonance

Crisostomo

Dang

Digambaranath

et al. 2015

Analytical Biochemistry

Self Cite

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show abstract

“…A␤ antibodies that act principally by sequestering the peripheral A␤ pool do not cross the BBB and are generally thought to clear A␤ from the brain by the so-called "peripheral sink" mechanism through binding of peripheral A␤, which according to some studies lessens the risk of potential central side effects of the antibody clearance therapy, such as neuroinflammation, vasogenic edema, and cerebral microhemorrhages (27)(28)(29)(30). Recent studies in patients with mild AD have shown beneficial effects of intravenous immunoglobulin preparation (Gammagard), which has been suggested to act as a peripheral sink agent containing sLRP1 and antibodies against diverse A␤ conformations (31,32).…”

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confidence: 99%