Clinical Information

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by joint inflammation and destruction. It is heterogeneous, with genetic and environmental factors contributing to its development.(1) There is a well-established link between an increased risk of developing RA and specific alleles of the human leukocyte antigen (HLA) complex including HLA-DRB1*0404, HLA-DRB1*0405, and HLA-DRB1*0101. It has been estimated that those HLA alleles are responsible for approximately 50% of the genetic susceptibility to RA.(1)

Recently, other genes have been identified that also influence the susceptibility of an individual to developing RA. The gene PTPN22 (protein tyrosine phosphatase, non-receptor type 22) encodes the protein Lyp, a phosphatase that is responsible, in part, for regulating T-cell activation. A particular single nucleotide polymorphism (SNP) in PTPN22, designated as 1858C->T, is found more frequently in individuals with autoimmune diseases, including RA, than in healthy control cohorts.(2) It has been proposed that the 1858C->T SNP alters the function of the Lyp, rendering the individual more susceptible to developing RA.(2) In addition, in patients diagnosed with RA, the presence of the T allele has been linked to certain disease phenotypes, including positivity for cyclic citrullinated peptide (CCP) antibodies (a marker for RA), earlier age at diagnosis, and increased rate of joint erosion.(3)