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.
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.
Johansson
Martin
M
Department of Rheumatology, University Hospital, Umeå, Sweden. martin.johansson@medicin.umu.se
Arlestig
Lisbeth
L
Hallmans
Göran
G
Rantapää-Dahlqvist
Solbritt
S
D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002956:Citrulline / Q000276:immunology; D017931:DNA Primers; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000276:immunology*; D012016:Reference Values; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D017931:DNA Primers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments; D002956:Citrulline; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases