Specific antibodies to soluble alpha-synuclein conformations in intravenous immunoglobulin preparations.
Alpha-synuclein is the major protein in Lewy bodies, the hallmark pathological finding in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although normally intracellular, it also can be secreted, so extracellular alpha-synuclein may contribute to neuronal injury. Serum antibodies to alpha-synuclein could exert protective effects by increasing alpha-synuclein's movement out of the brain and, if they cross the blood-brain barrier, by inhibiting its neurotoxic effects. The objective of this study was to measure antibody concentrations to alpha-synuclein monomer and soluble oligomers in three intravenous immunoglobulin (IVIG) preparations, Gamunex (Talecris Biotherapeutics), Gammagard (Baxter Healthcare) and Flebogamma (Grifols Biologicals). Antibodies were measured in native IVIG preparations and after antibody-antigen complex dissociation. IVIG's non-specific binding was subtracted from its total binding to alpha-synuclein to calculate specific anti-alpha-synuclein antibody concentrations. Specific antibodies to alpha-synuclein monomer and/or soluble oligomers were detected in all IVIG products. In native IVIG preparations, the highest anti-monomer concentrations were in Gammagard and the highest anti-oligomer concentrations were in Gamunex; the extent to which lot-to-lot variation may have contributed to these differences was not determined. Antibody-antigen complex dissociation had variable effects on these antibody levels. The IVIG preparations did not inhibit alpha-synuclein oligomer formation, although they changed the distribution and intensity of some oligomer bands on Western blots. The presence of antibodies to soluble alpha-synuclein conformations in IVIG preparations suggests that their effects should be studied in animal models of synucleinopathies, as a first step to determine their feasibility as a possible treatment for PD and other synucleinopathies.
Patrias
L M
LM
Departments of Neurology ResearchBiostatistics, William Beaumont Hospital Research Institute, Royal Oak, MI 48073, USA.
Klaver
A C
AC
Coffey
M P
MP
Loeffler
D A
DA
D000906:Antibodies / Q000276:immunology*; D001667:Binding, Competitive; D015153:Blotting, Western; D002210:Caprylates / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D012995:Solubility; D051844:alpha-Synuclein / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D002210:Caprylates; D016756:Immunoglobulins, Intravenous; D051844:alpha-Synuclein