We have recently shown that thyroperoxidase antibody positivity impairs the thyroidal response to hCG stimulation, which may suggest that this is a mechanism through which thyroid autoimmunity acts as a risk factor for thyroid disease.
Protein tyrosine phosphatase type 22 (PTPN22) and Cytotoxic T lymphocyte antigen-4 (CTLA-4) are two of these genes, and single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with several autoimmune diseases.
Recently, a gain of function variant C1858T of the lymphoid-specific protein tyrosine phosphatase non-receptor (LYP, PTPN22) gene has been reported to be associated with several autoimmune disorders including Graves' disease, type 1 diabetes, rheumatoid arthritis and vitiligo.
A protein tyrosine phosphatase (PTPN22) present in lymphocytes is an important negative regulator of signal transduction for the T-cell receptor-MHC complex and has been associated with autoimmune disorders that produce autoantibodies.
To examine the impact of low birth weight on the development of thyroid autoimmunity, we studied whether within-twin-cohort and within-twin-pair differences in birth weight are associated with differences in the serum concentration of TPOAb and TgAb in adult life.
The missense R620W polymorphism, rs 2476601, in PTPN22 gene at the nucleotide 1858 in codon 620 (620Arg > Trp) has been associated with autoimmune diseases.
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE).
The 1858C>T (R620W) functional polymorphism of the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (Lyp), has been associated with susceptibility to a number of autoimmune disorders, including generalized vitiligo.
The functional R620W (C1858T) polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, a member of the PTPs that negatively regulate T-cell activation, has been recently associated with susceptibility to various autoimmune diseases.
A higher frequency of APC (13.3%) and PA (4%) was found in cases than in controls (p=0.003), associated with other autoimmune diseases (p=0.003), but not with insulin or PTPN22 polymorphisms.
These results confirm the influence of PTPN22 in autoimmunity and indicate that autoimmune phenotypes could represent pleiotropic outcomes of nonspecific disease genes that underlie similar immunogenetic mechanisms.
Non-organ specific AAb (ANA, anti-Ro52, anti-Ro60, anti-La, anti-RNP) but not anti-thyroid peroxidase, anti-tissue transglutaminase or myositis-specific antibodies, were more frequent in s-IBM patients, and 14/51 (27%) had another autoimmune disease (Sjögren's syndrome, thyroiditis, psoriasis, vitiligo).
The protein tyrosine phosphatase non-receptor 22 (PTPN22) 1858 C>T poly-morphic variant gene (rs2476601) displays an association with systemic lupus erythematosus (SLE) and other autoimmune diseases.
These findings highlight PTPN22 as a novel regulator of dectin-1 signals, providing a link between genetically conferred perturbations of innate receptor signaling and the risk of autoimmune disease.
Autoimmune diseases in the family increased the risk of thyroid autoimmunity: TPOAb (OR: 2.2, <i>p</i> = 0.012), any autoantibody (OR: 1.7, <i>p</i> = 0.04), and both autoantibodies (OR: 2.2, <i>p</i> = 0.024).
Although numerous papers demonstrated the significant increase in the prevalence of thyroid autoimmunity (positive intrathyroidal lymphocyte infiltration and/or anti-thyroglobulin/thyroid peroxidase antibodies) in patients with thyroid cancers as compared to those with benign nodules, and also the significant increase in the prevalence of papillary thyroid cancer (PTC) in patients with thyroid autoimmunity as compared to those without, there are some crucial biases that should be taken into account for their interpretation.
These results indicate that the PTPN22 gene polymorphism independent of the SNP rs2476601 might be a supplementary risk factor to AITD, but not in T1D in Koreans, contradicting a major contributory influence of the PTPN22 gene in explaining common mechanism underlying multiple autoimmune diseases.
The association of subsets of SSc with the PTPN22R620W polymorphism further strengthens the classification of SSc within the spectrum of autoimmune diseases and strongly suggests the involvement of common susceptibility genes and similarly disordered immunoregulatory pathways.