Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant

T Vang, M Congia, MD Macis, L Musumeci, V Orrú… - Nature …, 2005 - nature.com
T Vang, M Congia, MD Macis, L Musumeci, V Orrú, P Zavattari, K Nika, L Tautz, K Taskén
Nature genetics, 2005nature.com
A SNP in the gene PTPN22 is associated with type 1 diabetes, rheumatoid arthritis, lupus,
Graves thyroiditis, Addison disease and other autoimmune disorders. T cells from carriers of
the predisposing allele produce less interleukin-2 upon TCR stimulation, and the encoded
phosphatase has higher catalytic activity and is a more potent negative regulator of T
lymphocyte activation. We conclude that the autoimmune-predisposing allele is a gain-of-
function mutant.
Abstract
A SNP in the gene PTPN22 is associated with type 1 diabetes, rheumatoid arthritis, lupus, Graves thyroiditis, Addison disease and other autoimmune disorders. T cells from carriers of the predisposing allele produce less interleukin-2 upon TCR stimulation, and the encoded phosphatase has higher catalytic activity and is a more potent negative regulator of T lymphocyte activation. We conclude that the autoimmune-predisposing allele is a gain-of-function mutant.
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