PTPN22 polymorphism and anti-cyclic citrullinated peptide antibodies in combination strongly predicts future onset of rheumatoid arthritis and has a specificity of 100% for the disease

Arthritis Res Ther. 2006;8(1):R19. doi: 10.1186/ar1868.


We analysed relationships between the PTPN22 1858 polymorphism and antibodies to cyclic citrullinated peptide (CCP), rheumatoid factors (RFs) and the shared epitope (SE) gene (HLA-DRB1*0404 or 0401) and determined their combined predictive value for rheumatoid arthritis (RA) in individuals who subsequently developed RA. This case-control study was nested within the Medical Biobank of Northern Sweden. Patients with RA (n = 92) were identified from amongst blood donors antedating onset of disease by a median of 2.4 (interquartile range 1.2 to 4.9) years. Matched controls were selected randomly from the same cohorts (n = 368). Anti-CCP antibodies and RFs were determined using enzyme-linked immunoassays. Genotyping was performed using an ABI PRISM 7900HT instrument and HLA-SE genes were identified using PCR sequence-specific primers. The 1858T allele and also carriage of T were associated with future onset of RA (odds ratio (OR) = 2.29, 95% confidence interval (CI) 1.45-3.61 and OR = 2.64, 95% CI 1.56-4.47, respectively). The combination of the 1858T variant and anti-CCP antibodies gave 100% specificity for the disease. None of the 368 controls expressed this combination. The PTPN22 1858T variant and anti-CCP antibodies were clearly associated (OR = 3.80, 95% CI 1.51-9.57). A combination of the PTPN22 1858T variant and anti-CCP antibodies gave a much higher relative risk (>132.03) for developing RA than the combination of the T variant and HLA-SE (OR = 7.85). The PTPN22 1858T variant was associated with future development of RA. There was an association between the T variant and anti-CCP antibodies and their combination, found only among pre-patients, gives a very high relative risk for development of RA. The combination gave a specificity of 100% for diagnosing RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Base Sequence
  • Case-Control Studies
  • Chi-Square Distribution
  • Citrulline / immunology
  • DNA Primers
  • Female
  • Genetic Variation
  • Genotype
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Male
  • Peptide Fragments / immunology
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / immunology*
  • Reference Values
  • Sensitivity and Specificity


  • Autoantibodies
  • DNA Primers
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Peptide Fragments
  • Citrulline
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases