OBJECTIVES: Anti-citrullinated peptide antibodies (ACPA) and the C1858T missense 
single-nucleotide polymorphism (SNP) in the PTPN22 gene are both associated with 
the development of rheumatoid arthritis (RA). We investigated whether the 
combination of these two biomarkers yielded better test characteristics to 
predict progression from undifferentiated arthritis (UA) to RA compared with 
ACPA alone.
METHODS: A total of 394 individuals with UA from a Dutch population-based 
inception cohort were included in this study. At baseline, ACPA were measured 
and the PTPN22 C1858T and HLA-DRB1 genotypes determined. Progression to RA was 
monitored at 1 yr after entry into the cohort.
RESULTS: A priori, UA patients had a 35% (95% CI 30-40%) risk of developing RA, 
which increased to 66% (95% CI 57-75%) in patients who were ACPA-positive. There 
was an additional, although non-significant (P = 0.34), increase in RA risk to 
76% (95% CI 57-90%) when patients were positive for both ACPA and the PTPN22 
1858T-allele. The area under the receiver operator characteristic curve 
increased from 0.68 for ACPA-status alone to 0.70 for the combination of 
ACPA-status and the PTPN22 C1858T polymorphism. In logistic regression analysis, 
ACPA predicted RA-development independent of PTPN22, while the PTPN22 
polymorphism had no independent effect. In HLA-DRB1 shared epitope positive, 
ACPA-positive UA patients, ACPA-levels were significantly increased in PTPN22 
1858T allele carriers compared with non-1858T carriers.
CONCLUSIONS: In this Dutch cohort of UA-patients, the PTPN22 1858T allele does 
not markedly improve individual decision-making to predict RA-development over 
ACPA alone, but it is associated with higher ACPA-levels.