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

VANG T;CONGIA M;MACIS MD;MUSUMECI L;ORRU', VALERIA;ZAVATTARI, PATRIZIA;NIKA K;TAUTZ L;TASKEN K;CUCCA F;MUSTELIN T;BOTTINI N.

2005-01-01

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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.