autoimmune disease with an annual incidence of 10.5/100,000 in Asian Indians [1]. It is characterized by T cell-mediated destruction of pancreatic beta cells influenced by multiple genetic factors, such as HLA-II locus on chromosome 6p21.3 [2], insulin gene on 11p15.5 [3] and the CTLA4 locus on 2q33 [4], all of these are involved in T cell activation, immune homeostasis and development of T cel...

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-fu...

AIM Autoimmune thyroid disease (AITD) is a multifactorial disease with a genetic predisposition. The protein tyrosine phosphatase-22 (PTPN-22) gene is a powerful inhibitor of T-cell activation. The aim of this study was to compare messenger RNA (mRNA) PTPN22 expression between healthy persons and patients with hypothyroidism and with their affected relatives. METHODS This was a cross-sectiona...

In order to explore the role of IL-22 in the pathogenesis of CRS, we observed the expression of IL-22 and associated factors in chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Immunohistochemical staining was applied to detect the expression of IL-22, IL-22R, STAT3, retinoic acid orphan receptor C (RORC) and aryl hydrocarbon recptor (A...

LYP, the protein product of the protein tyrosine phosphatase gene PTPN22 located on human chromosome 1p13.2, is involved in downregulation of T cell signaling through its interaction with C-terminal Src tyrosine kinase (Csk) (Cloutier and Veillette, 1996), by phosphorylation of regulatory tyrosines on the Src family kinase Lck (Cloutier and Veillette, 1999). A missense mutation of this gene (C1...

Type 1 diabetes is an autoimmune disease caused by the destruction of pancreatic beta cells by autoreactive T cells. Among the genetic variants associated with type 1 diabetes, the C1858T (Lyp) polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene alters the function of T cells but also of B cells in innate and adaptive immunity. The Lyp variant was shown to dimini...

Multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus, are associated with an allelic variant of protein tyrosine phosphatase nonreceptor 22 (PTPN22), which encodes the protein LYP. To model the human disease-linked variant LYP-R620W, we generated knockin mice expressing the analogous mutation, R619W, in the murine orthol...

Several candidate-genes for Rheumatoid Arthritis are studied using multi-marker association scores based on 839 cases and 855 unrelated controls from the North American Rheumatoid Arthritis Consortium (NARAC) as part of the Genetic Analysis Workshop 15 data. Strong signals previously identified on PTPN22 and PADI4 were repeated in our findings. We also found significant association evidence tha...

RA is a common autoimmune disease with a complex aetiology in which genetic and environmental factors contribute to disease. The genetic component of RA is largely undefined and, up until very recently, there were only two reproducible associations. The strongest of these associations is of genes within the HLA region, particularly the HLA-DRB1 gene. A second, more modest, association identifie...