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 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).


CONCLUSIONS
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.
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
D001323:Autoantibodies; D005819:Genetic Markers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22