| Autor: |
Chuang, W.-Y., Ströbel, P., Belharazem, D., Rieckmann, P., Toyka, K. V., Nix, W., Schalke, B., Gold, R., Kiefer, R., Klinker, E., Opitz, A., Inoue, M., Kuo, T.-t., Müller-Hermelink, H. K., Marx, A. |
| Předmět: |
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| Zdroj: |
Genes & Immunity; Dec2009, Vol. 10 Issue 8, p667-672, 6p, 2 Charts, 2 Graphs |
| Abstrakt: |
Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) inhibits T-cell activation and interleukin-2 (IL-2) production. The PTPN22gain-of-function+1858T(+) genotypes predispose to multiple autoimmune diseases, including early-onset (non-thymomatous) myasthenia gravis (MG). The disease association and the requirement of IL-2/IL-2 receptor signaling for intrathymic, negative T-cell selection have suggested that these genotypes may weaken T-cell receptor (TCR) signaling and impair the deletion of autoreactive T cells. Evidence for this hypothesis is missing. Thymoma-associated MG, which depends on intratumorous generation and export of mature autoreactive CD4(+) T cells, is a model of autoimmunity because of central tolerance failure. Here, we analyzed the PTPN22 +1858C/T single nucleotide polymorphism in 426 German Caucasian individuals, including 125 thymoma patients (79 with MG), and investigated intratumorous IL-2 expression levels. Unlike two previous studies on French and Swedish patients, we found strong association of PTPN22 +1858T(+) genotypes not only with early-onset MG (P=0.00034) but also with thymoma-associated MG (P=0.0028). IL-2 expression in thymomas with PTPN22 +1858T(+) genotypes (P=0.028) was lower, implying weaker TCR signaling. We conclude that the PTPN22gain-of-function variant biases towards MG in a subgroup of thymoma patients possibly by impeding central tolerance induction. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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