Genetic studies in the systemic sclerosis (SSc), an autoimmune disease that clinically manifests with dermal and internal organ fibrosis and small vessel vasculopathy, have identified multiple susceptibility genes including HLA-class II, PTPN22, IRF5, and STAT4 which have also been associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE).
Haplotype analysis showed strong linkage disequilibrium D' = 0.98 for PTPN22 -1123G>C and +1858C>T polymorphisms, but haplotypes were not associated with SLE.
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.
In conclusion, this meta-analysis confirms that the PTPN22C1858T polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.
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.
IRF5 is involved in the production of rheumatoid arthritis (RA) cytokines, and SLE already shares with RA one genetic factor within the tyrosine phosphatase PTPN22 gene.
Many key relevant candidate genes (such as PTPN22, LRP1B etc.) displaying differential changes in H3K4me3 in SLE versus controls (rheumatoid arthritis patients, healthy subjects) were identified.
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.
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.
Polymorphisms in PTPN22 are associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type 1 diabetes.
Several multiple, large-scale, genetic studies on autoimmune-disease-associated SNPs have been reported recently: peptidylarginine deiminase type 4 (PADI4) in rheumatoid arthritis (RA); solute carrier family 22 members 4 and 5 (SLC22A4 and 5) in RA and Crohn's disease (CD); programmed cell death 1 (PDCD1) in systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), and RA; and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in T1D, RA, and SLE.
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.
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.
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.