Auto-antibodies, HLA and PTPN22: Susceptibility markers for rheumatoid arthritis

Objective. To analyse the relationship between the presence of auto-antibodies [rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)], HLA-DRB1 alleles and PTPN22 1858 C/T polymorphism and test the value of their combination as susceptibility markers for rheumatoid arthritis (RA). Methods. Patients with early arthritis were included. At entry in the cohort or during follow-up, 191 patients fulfilled the criteria for RA and 184 individuals suffered from other arthropathies. RF was measured by nephelometry and anti-CCP antibody by enzyme-linked immunosorbent assay. HLA class II alleles were determined by polymerase chain reaction. Samples were genotyped for PTPN22 1858C/T variants using a TaqMan 5′-allele discrimination assay. Results. The presence of shared epitope (SE) alleles was strongly associated with anti-CCP and RF-positive RA [P = 7.05 × 10-10, odds ratio (OR) 4.57, 95% confidence interval (CI) 2.76-7.57 and P = 1.68 × 10-6, OR 2.99, 95%; CI 1.89-4.74, respectively). The combination of the PTPN22 1858T variant and anti-CCP antibodies gave a high specificity for the disease, and was significantly associated with RA (P = 8.86 × 10-5, OR 10.05, 95% CI 1.88-53.73). Conclusion. The combination of the T variant of the 1858 polymorphism of the PTPN22 gene in combination with the presence of anti-CCP antibodies, preferentially in a SE-positive individual, is associated with the development of RA. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.