Development of a maturing T-cell-mediated immune response in patients with idiopathic Parkinson's disease receiving r-metHuGDNF via continuous intraputaminal infusion.

Full 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.

Author information

Author/s: Tatarewicz, Suzanna M (SM); Wei, Xin (X); Gupta, Shalini (S); Masterman, Donna (D); Swanson, Steven J (SJ); Moxness, Michael S (MS);

Affiliation: Clinical Immunology, Medical Sciences, Amgen Inc, Thousand Oaks, CA 91320-1799, USA. suzannat(-atsign-)amgen.com

Journal and publication information

Publication Type: Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Validation Studies

Journal: Journal of clinical immunology (J Clin Immunol), published in United States. (Language: eng)

Reference: 2007-Nov; vol 27 (issue 6) : pp 620-7

Dates: Created 2007/11/13; Completed 2008/02/26;

PMID: 17629719, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Binding Sites, Antibody
Cell Differentiation - immunology
Clone Cells
Double-Blind Method
Glial Cell Line-Derived Neurotrophic Factor - administration & dosage; genetics; immunology; metabolism; therapeutic use
Humans
Immunoglobulin Class Switching - immunology
Immunoglobulin G - biosynthesis; metabolism

Immunoglobulin M - biosynthesis; metabolism
Infusion Pumps, Implantable
Injections, Intraventricular
Longitudinal Studies
Mice
Parkinson Disease - immunology; pathology; therapy
Putamen
Recombinant Proteins - administration & dosage; immunology; metabolism
T-Lymphocyte Subsets - immunology; metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Binding Sites, Antibody (0) ; Glial Cell Line-Derived Neurotrophic Factor (0) ; Immunoglobulin G (0) ; Immunoglobulin M (0) ; Recombinant Proteins (0)

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