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

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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.

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Acknowledgment

We would like to thank Dr. Eugen Koren for his counsel during the immunoassay analysis. We would like to thank Dr. Annie DeGroot for providing the T-cell epitope predictions.

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Authors and Affiliations

  1. Clinical Immunology, Medical Sciences, Amgen, Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA

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

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  1. Suzanna M. Tatarewicz
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  2. Xin Wei
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  3. Shalini Gupta
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  4. Donna Masterman
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Correspondence to Suzanna M. Tatarewicz.

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Tatarewicz, S.M., Wei, X., Gupta, S. et al. Development of a Maturing T-Cell-Mediated Immune Response in Patients with Idiopathic Parkinson’s Disease Receiving r-metHuGDNF Via Continuous Intraputaminal Infusion. J Clin Immunol 27, 620–627 (2007). https://doi.org/10.1007/s10875-007-9117-8

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  • DOI: https://doi.org/10.1007/s10875-007-9117-8

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