Predictive Value of Autoantibodies in Clinically Suspect Arthralgia and Risk for RA

The presence of the certain autoantibodies accurately predicts a person's risk for progression from clinically suspect arthralgia to rheumatoid arthritis.

The presence of the certain autoantibodies, in particular, anti-citrullinated protein antibody (ACPA), rheumatoid factor (RF), and antibodies against anti-carbamylated protein (anti-CarP), accurately predict a person’s risk for progression from clinically suspect arthralgia (CSA) to rheumatoid arthritis (RA). The results of the study were published in Rheumatology.

A total of 241 consecutive patients were included in a CSA cohort at a Dutch rheumatology clinic between April 2012 and March 2015. Mean patient age was 44 years, 78% of the participants were female, and 93% were white. A family history of RA was reported in 30% of the patients. 

The baseline ACPA, RF, and anti-CarP autoantibody status of all participants was examined with respect to their future risk for RA developing. Follow-up visits were scheduled at 4, 12, and 24 months.

Univariable associations for RA development were reported for ACPA (hazard ratio [HR], 8.5; 95% CI, 4.7-15.4), RF (HR, 5.1; 95% CI, 2.8-9.3), and anti-CarP antibodies (HR, 3.9; 95% CI, 1.9-7.7). After multivariable Cox proportional hazards regression analyses, only ACPA was found to be independently associated with a person’s risk for RA developing (HR, 5.1; 95% CI, 2.0-13.2).

Evaluation of autoantibody-negative patients with CSA showed that ACPA-negative/RF-positive individuals had an HR of 2.6 (95% CI, 1.04-6.6), ACPA-positive/RF-negative patients had an HR of 8.0 (95% CI, 2.4-27.4), and ACPA-positive/RF-positive participants had an HR of 10.5 (95% CI, 5.4-20.6).

Positive predictive values for the development of RA within 2 years were 38% for ACPA-negative/RF-positive patients, 50% for ACPA-positive/RF-negative participants, and 67% for ACPA-positive/RF-positive individuals.

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Higher ACPA levels were not associated with a significantly increased risk for progression to RA, whereas higher RF levels were. During follow-up, autoantibody levels remained stable.

Among the autoantibodies assessed, ACPA conferred the highest risk for the development of RA and had an additive value to RF. Of note, however, is that RA did not develop in >30% of ACPA-positive/RF-positive CSA patients during the 2-year follow-up. The researchers concluded that within the CSA population, the presence of ACPA alone or a combination of ACPA and RF is insufficient for the accurate identification of imminent ACPA-positive RA. Additional biomarkers are needed for optimal prediction.


Ten Brinck RM, van Steenbergen HW, van Delft MAM, et al. The risk of individual autoantibodies, autoantibody combinations and levels for arthritis development in clinically suspect arthralgia [published online September 11, 2017]. Rheumatology (Oxford). doi:10.1093/rheumatology/kex340