Keywords :
Alleles; Antibodies/pharmacology; Autoimmune Diseases/enzymology/genetics/immunology; Catalysis; Diabetes Mellitus, Type 1/enzymology/genetics/immunology; Female; Gene Frequency; Genetic Predisposition to Disease; Heterozygote; Humans; Interleukin-2/metabolism; Italy; Lymphocyte Activation; Male; Mutation; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Protein Tyrosine Phosphatases/genetics; Receptors, Antigen, T-Cell/drug effects/metabolism; T-Lymphocytes/enzymology/immunology
Abstract :
[en] 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.
Research Center/Unit :
Program on Inflammatory Disease Research, Infectious and Inflammatory Disease Center, The Burnham Institute
Dipartimento di Scienze Biomediche e Biotecnologie, Universita` degli Studi di Cagliari
Department of Orthopaedic Surgery and Institute for Genetic Medicine, University of Southern California Keck School of Medicine
The Biotechnology Centre, University of Oslo
Scopus citations®
without self-citations
570
