Antibody concentrations to Abeta1-42 monomer and soluble oligomers in untreated and antibody-antigen-dissociated intravenous immunoglobulin preparations.
Cognitive improvement in Alzheimer's disease (AD) patients treated with intravenous immunoglobulin (IvIg) has been attributed to its antibodies to amyloid beta (Abeta). We compared the concentrations of specific antibodies to soluble Abeta1-42 conformations, namely Abeta1-42 monomer and Abeta1-42 soluble oligomers, between three IvIg preparations, Gamunex, Gammagard, and Flebogamma. To determine specific antibody concentrations to these Abeta1-42 conformations, nonspecific binding of the IvIg preparations to the Abeta reverse sequence, Abeta42-1, was subtracted. These antibodies were measured in untreated IvIg preparations and also after they were treated to dissociate antibody-antigen complexes, because this procedure has been reported to increase the detectable levels of serum anti-Abeta antibodies. Antibody levels to Abeta1-42 monomer were significantly higher in untreated Gamunex than in the other two IvIg preparations, and antibody-antigen dissociation increased the measured anti-Abeta monomer concentrations in Gamunex and Gammagard. Dissociated Gamunex and Gammagard had higher anti-Abeta monomer levels than Flebogamma. Generally similar results were found for antibodies to soluble Abeta1-42 oligomers, with the exception that after antibody-antigen dissociation, only Gammagard had significantly higher antibody levels than Flebogamma. These differences in antibody concentrations to Abeta1-42 conformations (particularly to Abeta1-42 soluble oligomers, thought to be the most neurotoxic conformation of soluble Abeta) and the increased availability of these antibodies after antibody-antigen complex dissociation have important implications for IvIg treatment of AD patients.
Klaver
Andrea C
AC
Division of Neurology, Beaumont Research Institute, William Beaumont Hospital, Suite 507, Royal Oak, MI 48073, USA. Andrea.Klaver@beaumont.edu
Finke
John M
JM
Digambaranath
Jyothi
J
Balasubramaniam
Mamtha
M
Loeffler
David A
DA
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism; D002210:Caprylates / Q000737:chemistry* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis* / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000737:chemistry* / Q000627:therapeutic use; D007158:Immunologic Techniques; D007167:Immunotherapy; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D012015:Reference Standards
D016229:Amyloid beta-Peptides; D000936:Antigen-Antibody Complex; D002210:Caprylates; D000939:Epitopes; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D010446:Peptide Fragments