Journal of Clinical Immunology

, Volume 27, Issue 6, pp 620–627

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

  • Suzanna M. Tatarewicz
  • Xin Wei
  • Shalini Gupta
  • Donna Masterman
  • Steven J. Swanson
  • Michael S. Moxness
Article

DOI: 10.1007/s10875-007-9117-8

Cite this article as:
Tatarewicz, S.M., Wei, X., Gupta, S. et al. J Clin Immunol (2007) 27: 620. doi:10.1007/s10875-007-9117-8

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.

Keywords

GDNFParkinson’s diseaseimmunoglobulin class switchT-cell epitopesimmunoassayneutralizing antibodiesin silico

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Suzanna M. Tatarewicz
    • 1
  • Xin Wei
    • 1
  • Shalini Gupta
    • 1
  • Donna Masterman
    • 1
  • Steven J. Swanson
    • 1
  • Michael S. Moxness
    • 1
  1. 1.Clinical ImmunologyMedical Sciences, Amgen, Inc.Thousand OaksUSA