Since the expression of the negative T-cell signaling molecule PTPN22 is increased and a marker of poor prognosis in SLE, we tested the influence of its missense risk allele Trp<sup>620</sup> (rs2476601C>T) on Treg frequency.
Our data demonstrated the aberrant expression of circRNAs in patients with SLE compared with healthy controls; circPTPN22 might function as a diagnostic and disease severity indicator in SLE.
PTPN22 (that encodes a tyrosine phosphatase) has been associated with the development of several autoimmune diseases, including type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus.
In summary, PTPN22rs2476601 was significantly interrelated with SLE and contributed to susceptibility and development of SLE in Americans, Europeans and Africans in this analysis, while their relationship needs to be validated in Africans by future research.
Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies.
The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: padj = 6.07e-004, OR=0.57; rs3811021C: padj = 4.68e-005, OR=0.65) and RA (rs1217414T: padj = 2.01e-008, OR=0.26; rs3811021C: padj = 0.028, OR=0.70).
Haplotype analysis showed strong linkage disequilibrium D' = 0.98 for PTPN22 -1123G>C and +1858C>T polymorphisms, but haplotypes were not associated with SLE.
This study may provide an additional evidence for the association between IRF5 and PTPN22 and lupus susceptibility and may exclude it for CD28, IL2RA, and KIF5A.
PDCs from SLE patients carrying the disease-associated PTPN22 variant LypW showed a reduced capacity for TLR-7 agonist-induced type I IFN production, even though LypW carriers displayed systemic type I IFN activation comparable with that observed in noncarriers.
Human genetics studies have shown that a single-nucleotide polymorphism in PTPN22 is often mutated in patients suffering from autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosis.
The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus.
The meta-analysis showed that the 1858C/T polymorphism of the PTPN22 gene is correlated with systemic lupus erythematosus susceptibility, when assessed by distribution characteristics such as nationality, race, and region.
Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations.
Polymorphisms in PTPN22 are associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type 1 diabetes.
For example, genetic polymorphisms in the Protein Tyrosine Phosphatase-22 (PTPN22) gene have reproducibly shown to have association with systemic lupus erythematosus (SLE), Graves' disease (GD), rheumatoid arthritis (RA) and multiple sclerosis (MS), but not with psoriasis.
This work has investigated the possible association between PTPN22C1858T (rs2476601) polymorphism and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in a Colombian population.
Although the PTPN22 1858 T allele is found at decreased frequency in Southern Europe, including Crete, an association was found between this allele and SLE in the population studied.