Chuang, W-Y and Stroebel, P. and Belharazem, D. and Rieckmann, P. and Toyka, K. V. and Nix, W. and Schalke, B. and Gold, R. and Kiefer, R. and Klinker, E. and Opitz, A. and Inoue, M. and Kuo, T-T and Mueller-Hermelink, H. K. and Marx, A. (2009) The PTPN22(gain-of-function)+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis. GENES AND IMMUNITY, 10 (8). pp. 667-672. ISSN 1466-4879,
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Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) inhibits T-cell activation and interleukin-2 (IL-2) production. The PTPN22(gain-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 PTPN22(gain-of-function) variant biases towards MG in a subgroup of thymoma patients possibly by impeding central tolerance induction. Genes and Immunity (2009) 10, 667-672; doi: 10.1038/gene.2009.64; publishedonline 20 August 2009
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LYMPHOID TYROSINE PHOSPHATASE; AUTOIMMUNE-DISEASE; GENETIC ASSOCIATION; NEGATIVE SELECTION; CELL SUBSET; T-CELLS; PTPN22; POLYMORPHISM; VARIANT; SUSCEPTIBILITY; PTPN22; CTLA-4; myasthenia; negative selection; thymoma |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Aug 2020 06:41 |
| Last Modified: | 31 Aug 2020 06:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28027 |
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