Alfred Weber, Austria
Baxalta Innovations GmbH, a Takeda company R&D Plasma Derived Therapies, Pharmaceutical SciencePresenter of 1 Presentation
DETECTION AND CHARACTERIZATION OF SPECIFIC ANTI-APOLIPOPROTEIN E4 IGG ANTIBODIES IN HUMAN PLASMA AND AN INTRAVENOUS IMMUNOGLOBULIN PREPARATION (GAMMAGARD LIQUID)
Abstract
Background and Aims
Apoliprotein E4 (apoE4) is the strongest genetic risk factor for Alzheimer’s Disease although the detailed method of action is still unclear. Kim et al (JEM 209, 2149) demonstrated that a monoclonal anti-apoE4 antibody reduced the amyloid deposition in an AD mouse model. These data prompted us to investigate human plasma and the intravenous immunoglobulin G (IVIG) preparation Gammagard Liquid (GGL) for the presence of naturally occurring anti-apoE4 immunoglobulin G (IgG) antibodies.
Methods
A direct ELISA with purified human apoE4 (Sigma) was used for the detection of anti-apoE4 IgG in a human reference plasma pool and several lots of GGL. The binding of natural occurring anti-apoE4 IgGs was compared with that of a monoclonal and a polyclonal anti-apoE4 preparation. Binding specificity was checked by competition studies using purified apoE4, apoE3 and apoE2.
Results
Human plasma and GGL contain anti-apoE4 IgG with EC50 binding values in the low one-digit µg/mL range. Binding to plate-bound apoE4 was shown to be specific as it could be dose-dependently inhibited by apoE4 in solution and by a monoclonal anti-apoE4 antibody. In contrast, purified apoE2 and apoE3 did not dose-dependently compete with binding of anti-apoE4 IgG to apoE4 suggesting the presence of conformation-specific antibodies specifically targeting apoE4.
Conclusions
Specific human naturally occurring anti-apoE4 IgGs, described to our best knowledge in plasma and IVIG for the first time, add to the list of rare examples that also naturally occurring IgG antibodies can be endowed with specific binding to conformationally different forms of proteins.