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Anti-aβ oligomer IgG and surface sialic acid in intravenous immunoglobulin: measurement and correlation with clinical outcomes in Alzheimer's disease treatment.

Kwon H, Crisostomo AC, Smalls HM, Finke JM - PLoS ONE (2015)

Bottom Line: The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous immunoglobulin (IVIG) using two complementary surface plasmon resonance methods.The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam.These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous immunoglobulin (IVIG) using two complementary surface plasmon resonance methods. These comparisons were performed to identify if an elevated fraction existed in Gammagard, which reported small putative benefits in a recent Phase III clinical trial for Alzheimer's Disease. The fraction of anti-oligomeric Aβ IgG was found to be higher in Octagam, for which no cognitive benefits were reported. The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam. These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products. A combined analysis of sialic acid in anti-oligomeric Aβ IgG did reveal a notable finding that this subgroup exhibited a high degree of surface sialic acid lacking the conventional α2,6 linkage. These results demonstrate that the IVIG antibodies used to engage oligomeric Aβ in both Gammagard and Octagam clinical trials did not possess α2,6-linked surface sialic acid at the time of administration. Anti-oligomeric Aβ IgG with α2,6 linkages remains untested as an AD treatment.

No MeSH data available.


Related in: MedlinePlus

The fraction of anti-OAx IgG is higher in Octagam than in Gammagard.FOAx+IVIG in IVIG products Octagam (OCT) and Gammagard (GG) was determined by CFCA. Error bars indicate standard deviations (n = 3) and the statistical significance of the difference between the two means is shown (p = 0.10).
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pone.0120420.g003: The fraction of anti-OAx IgG is higher in Octagam than in Gammagard.FOAx+IVIG in IVIG products Octagam (OCT) and Gammagard (GG) was determined by CFCA. Error bars indicate standard deviations (n = 3) and the statistical significance of the difference between the two means is shown (p = 0.10).

Mentions: CFCA was used to measure and compare FOAβ+IVIG in Octagam and Gammagard (Fig 3). The result was that FOAβ+IVIG for Octagam (0.00025) is approximately twice that of Gammagard (0.00012). The concentration of Octagam OAx+ IgG was reported at approximately 1.5 times that of Gammagard in a previous ELISA study [19]. As a possible explanation for the discrepancy in magnitude, Aβ peptides in the previous study had been disaggregated prior to immobilization. Nonetheless, both studies find that Octagam has a higher fraction of Ax-binding IgG than Gammagard.


Anti-aβ oligomer IgG and surface sialic acid in intravenous immunoglobulin: measurement and correlation with clinical outcomes in Alzheimer's disease treatment.

Kwon H, Crisostomo AC, Smalls HM, Finke JM - PLoS ONE (2015)

The fraction of anti-OAx IgG is higher in Octagam than in Gammagard.FOAx+IVIG in IVIG products Octagam (OCT) and Gammagard (GG) was determined by CFCA. Error bars indicate standard deviations (n = 3) and the statistical significance of the difference between the two means is shown (p = 0.10).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380445&req=5

pone.0120420.g003: The fraction of anti-OAx IgG is higher in Octagam than in Gammagard.FOAx+IVIG in IVIG products Octagam (OCT) and Gammagard (GG) was determined by CFCA. Error bars indicate standard deviations (n = 3) and the statistical significance of the difference between the two means is shown (p = 0.10).
Mentions: CFCA was used to measure and compare FOAβ+IVIG in Octagam and Gammagard (Fig 3). The result was that FOAβ+IVIG for Octagam (0.00025) is approximately twice that of Gammagard (0.00012). The concentration of Octagam OAx+ IgG was reported at approximately 1.5 times that of Gammagard in a previous ELISA study [19]. As a possible explanation for the discrepancy in magnitude, Aβ peptides in the previous study had been disaggregated prior to immobilization. Nonetheless, both studies find that Octagam has a higher fraction of Ax-binding IgG than Gammagard.

Bottom Line: The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous immunoglobulin (IVIG) using two complementary surface plasmon resonance methods.The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam.These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous immunoglobulin (IVIG) using two complementary surface plasmon resonance methods. These comparisons were performed to identify if an elevated fraction existed in Gammagard, which reported small putative benefits in a recent Phase III clinical trial for Alzheimer's Disease. The fraction of anti-oligomeric Aβ IgG was found to be higher in Octagam, for which no cognitive benefits were reported. The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam. These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products. A combined analysis of sialic acid in anti-oligomeric Aβ IgG did reveal a notable finding that this subgroup exhibited a high degree of surface sialic acid lacking the conventional α2,6 linkage. These results demonstrate that the IVIG antibodies used to engage oligomeric Aβ in both Gammagard and Octagam clinical trials did not possess α2,6-linked surface sialic acid at the time of administration. Anti-oligomeric Aβ IgG with α2,6 linkages remains untested as an AD treatment.

No MeSH data available.


Related in: MedlinePlus