title: Development of a maturing T-cell-mediated immune response in patients with idiopathic Parkinson's disease receiving r-metHuGDNF via continuous intraputaminal infusion.
abstract: The development of a maturing T-cell-mediated immune response was characterized in Parkinson's disease subjects receiving recombinant human glial-derived neurotrophic factor (r-metHuGDNF) via continuous bilateral intraputaminal infusion. Eighteen of 34 subjects tested positive for anti-r-metHuGDNF-binding antibodies. Four subjects developed neutralizing activity, three of which demonstrated classic immunoglobulin class switching from IgM to IgG. An increase of anti-r-metHuGDNF IgG-binding antibodies correlated with the development of neutralizing activity. All serum samples from two subjects with neutralizing activity were characterized for IgG subclasses. These data revealed an initial anti-r-metHuGDNF IgG population where IgG1 >> IgG2 >> IgG4, and IgG3 concentrations were negligible. However, continued antigenic stimulation resulted in concentration changes where IgG4 > IgG1> IgG2, indicating a mature immune response. In addition, using in silico techniques, two immunodominant MHC class II T-cell epitopes were predicted for the native GDNF sequence. These data demonstrate development of a mature T-cell-mediated immune response in these subjects.
authors.affiliation: Clinical Immunology, Medical Sciences, Amgen Inc, Thousand Oaks, CA 91320-1799, USA. suzannat@amgen.com
authors.forename: Suzanna M
authors.initials: SM
authors.lastname: Tatarewicz
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.forename: Shalini
authors.initials: S
authors.lastname: Gupta
authors.forename: Donna
authors.initials: D
authors.lastname: Masterman
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Swanson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Moxness
mesh_terms: D000818:Animals; D001666:Binding Sites, Antibody; D002454:Cell Differentiation / Q000276:immunology*; D002999:Clone Cells; D004311:Double-Blind Method; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D007276:Injections, Intraventricular; D008137:Longitudinal Studies; D051379:Mice; D010300:Parkinson Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011699:Putamen; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins