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 x 10(-10), odds ratio (OR) 4.57, 95% 
confidence interval (CI) 2.76-7.57 and P = 1.68 x 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 x 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.