OBJECTIVES: To evaluate the predictive value of TNFRII 196R, PTPN22 1858T and 
HLA-shared epitope (SE) alleles, RFs and anti-citrullinated protein antibodies 
(ACPAs) for RA diagnosis in a cohort of patients with very early arthritis.
METHODS: We followed up 284 patients who had swelling of at least two joints 
that had persisted for longer than 4 weeks but had been evolving for <6 months. 
At 2 yrs, patients were classified as having RA or non-RA rheumatic diseases 
according to the ACR criteria. Patients were genotyped with respect to TNFRII 
196M/R and PTPN22 1858C/T polymorphisms and HLA-SE. The presence of IgA, IgG and 
IgM RF isotypes and ACPA was sought in sera collected at disease onset.
RESULTS: HLA-SE alleles alone, concomitant presence of TNFRII 196R and PTPN22 
1858T alleles, IgA, IgG and IgM RF alone and ACPA were found to be significantly 
associated with RA diagnosis. Using logistic regression analysis, the 
concomitant presence of RF and ACPA at disease onset was the best association to 
predict RA diagnosis. In patients (n = 34) who did not fulfil the ACR criteria 
for RA at inclusion but who progressed to ACR positivity, the study of the 
genetic risk markers did not contribute to predict RA diagnosis at 2 yrs.
CONCLUSIONS: PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the 
predictive value of RF and ACPA for RA diagnosis in our cohort, and do not 
contribute to an earlier diagnosis in undifferentiated patients initially 
negative for RF and ACPA.