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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Antibodies / pharmacology
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Autoimmune Diseases / enzymology*
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology
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Catalysis
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Diabetes Mellitus, Type 1 / enzymology*
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology
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Female
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Gene Frequency
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Genetic Predisposition to Disease
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Heterozygote
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Humans
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Interleukin-2 / metabolism
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Italy
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Lymphocyte Activation
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Male
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Mutation
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Polymorphism, Single Nucleotide*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 22
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Protein Tyrosine Phosphatases / genetics*
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Receptors, Antigen, T-Cell / drug effects
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
Substances
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Antibodies
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Interleukin-2
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Receptors, Antigen, T-Cell
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PTPN22 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 22
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Protein Tyrosine Phosphatases