Rheumatoid factor and anti-citrullinated peptide antibodies in the general population: hepatitis B and C virus association and 15-year-risk of rheumatoid arthritis

Objective The study aimed to determine the prevalence of rheumatoid factor (RF) and anti-citrullinated peptides (ACPA), to estimate the association with hepatitis B (HBV) or C (HCV) virus infections and the 15-year risk of developing RA in a large cohort from a Northern Italian region. Methods In 1998, 15,907 subjects between the ages of 18 and 75 were randomly selected 1:4 for HBV and HCV testing; more recently, we tested a subgroup of sera for RF (n=2196) and ACPA (n=2525). Administrative databases were searched after 15 years for incident RA diagnoses occurring between 1998 and 2013. Results RF was positive in 8.1% of cases with 10% of RF-positive subjects having HBsAg (p=0.004) and 9% anti-HCV. ACPA were detected in 4.8% of subjects with 5% of the ACPA-positive subjects having HBsAg and 5.9% anti-HCV. Older subjects had higher positivity rates for both RF and ACPA. HBsAg and anti-HCV were detected in 5.5% and 43% of sera, respectively. Over 15 years, 10 RA cases were recorded (9 women, median age at diagnosis 52 years) with RF previously positive in 2/10 and ACPA in 5/10 cases. RF and ACPA were associated with relative risks for developing RA of 5.7 (adjusted for HBsAg status; 95% CI 12-263) and 132 (95% CI 3 .8-463), respectively. Conclusion Our data in a large cohort from an unselected general population confirm a higher risk of RA development associated with ACPA compared to RF. HBV exposure correlates with RF but not with ACPA positivity.

Automated summary

The study found that the positivity rates of RF and ACPA increased with age, and HBV and HCV infections were associated with RF positivity but not with ACPA positivity. Over 15 years, 10 RA cases occurred, with a lower risk of developing RA associated with RF compared to ACPA.