1. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant.
- Author
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Vang T, Congia M, Macis MD, Musumeci L, Orrú V, Zavattari P, Nika K, Tautz L, Taskén K, Cucca F, Mustelin T, and Bottini N
- Subjects
- Alleles, Antibodies pharmacology, Autoimmune Diseases genetics, Autoimmune Diseases immunology, Catalysis, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 immunology, Female, Gene Frequency, Genetic Predisposition to Disease, Heterozygote, Humans, Interleukin-2 metabolism, Italy, Lymphocyte Activation, Male, Mutation, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Receptors, Antigen, T-Cell drug effects, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes enzymology, Autoimmune Diseases enzymology, Diabetes Mellitus, Type 1 enzymology, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatases genetics, T-Lymphocytes immunology
- 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.
- Published
- 2005
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