Development of a Maturing T-Cell-Mediated Immune Response in Patients with Idiopathic Parkinson’s Disease Receiving r-metHuGDNF Via Continuous Intraputaminal Infusion

• Published in: Journal of clinical immunology Vol. 27; no. 6; pp. 620 - 627
• Main Authors: Tatarewicz, Suzanna M., Wei, Xin, Gupta, Shalini, Masterman, Donna, Swanson, Steven J., Moxness, Michael S.
• Format: Journal Article
• Language: English
• Published: Netherlands 01.11.2007
• Subjects: Animals; Binding Sites, Antibody; Cell Differentiation - immunology; Clone Cells; Double-Blind Method; Glial Cell Line-Derived Neurotrophic Factor - administration & dosage; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - immunology; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial Cell Line-Derived Neurotrophic Factor - therapeutic use; Humans; Immunoglobulin Class Switching - immunology; Immunoglobulin G - biosynthesis; Immunoglobulin G - metabolism; Immunoglobulin M - biosynthesis; Immunoglobulin M - metabolism; Infusion Pumps, Implantable; Injections, Intraventricular; Longitudinal Studies; Mice; Parkinson Disease - immunology; Parkinson Disease - pathology; Parkinson Disease - therapy; Putamen; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-007-9117-8

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.