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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2009-12-2
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1476-5470
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pubmed:author |
pubmed-author:BelharazemDD,
pubmed-author:ChuangW-YWY,
pubmed-author:GoldRR,
pubmed-author:InoueMM,
pubmed-author:KüS HSH,
pubmed-author:KieferRR,
pubmed-author:KlinkerEE,
pubmed-author:Müller-HermelinkH KHK,
pubmed-author:NAVAMMJr,
pubmed-author:OpitzAA,
pubmed-author:RieckmannPP,
pubmed-author:SchalkeBB,
pubmed-author:StröbelPP,
pubmed-author:ToykaK VKV,
pubmed-author:ZhuR GRG
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pubmed:issnType |
Electronic
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
667-72
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19693092-Adolescent,
pubmed-meshheading:19693092-Adult,
pubmed-meshheading:19693092-Aged,
pubmed-meshheading:19693092-Aged, 80 and over,
pubmed-meshheading:19693092-Antigens, CD,
pubmed-meshheading:19693092-CTLA-4 Antigen,
pubmed-meshheading:19693092-European Continental Ancestry Group,
pubmed-meshheading:19693092-Female,
pubmed-meshheading:19693092-Genetic Predisposition to Disease,
pubmed-meshheading:19693092-Genotype,
pubmed-meshheading:19693092-Humans,
pubmed-meshheading:19693092-Interleukin-2,
pubmed-meshheading:19693092-Male,
pubmed-meshheading:19693092-Middle Aged,
pubmed-meshheading:19693092-Myasthenia Gravis,
pubmed-meshheading:19693092-Polymorphism, Single Nucleotide,
pubmed-meshheading:19693092-Protein Tyrosine Phosphatase, Non-Receptor Type 22,
pubmed-meshheading:19693092-Thymoma,
pubmed-meshheading:19693092-Thymus Neoplasms,
pubmed-meshheading:19693092-Young Adult
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pubmed:year |
2009
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pubmed:articleTitle |
The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis.
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pubmed:affiliation |
Institute of Pathology, University of Würzburg, Würzburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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