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

被引：53

作者：

Tatarewicz, Suzanna M. ^{[1
]}

Wei, Xin ^{[1
]}

Gupta, Shalini ^{[1
]}

Masterman, Donna ^{[1
]}

Swanson, Steven J. ^{[1
]}

Moxness, Michael S. ^{[1
]}

机构：

[1] Amgen Inc, Thousand Oaks, CA 91320 USA

来源：

JOURNAL OF CLINICAL IMMUNOLOGY | 2007年 / 27卷 / 06期

关键词：

GDNF; Parkinson's disease; immunoglobulin class switch; T-cell epitopes; immunoassay; neutralizing antibodies; in silico;

D O I：

10.1007/s10875-007-9117-8

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：620 / 627

页数：8

共 37 条

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