Objective: Patients presenting with both arthralgia and antibodies to cyclic citrullinated peptide (anti-CCP) have an increased risk of developing rheumatoid arthritis (RA). To further characterize this patient group and shed more light on its relation with clinically manifest early arthritis and established RA, an immunogenetic and serological analysis was performed.
Methods: In a group of 111 patients with anti-CCP positive arthralgia, anti-CCP levels and shared epitope (SE) status were determined. Data were compared to 125 and 128 anti-CCP-positive patients with early arthritis and established RA, respectively.
Results: In anti-CCP-positive arthralgia patients, the frequency of SE allele positivity is significantly lower when compared to anti-CCP positive early arthritis and established RA (58% vs. 80%, and 58% vs. 92%, respectively, both P < 0.001). Median anti-CCP levels were higher in the group of SE positive arthralgia patients compared to the group of SE-negative arthralgia patients (P = 0.02). Median anti-CCP levels were similar in the groups of SE positive arthralgia and arthritis patients.
Conclusions: The lower frequency of SE positivity in arthralgia patients compared to RA patients indicates that, compared to SE-positive patients, SE negative patients as a group go through a longer arthralgia phase, or alternatively have a lower risk for transition from anti-CCP positive arthralgia to RA. Furthermore, the present results suggest that in this early stage the effect of the SE on disease risk may be mediated through higher anti-CCP levels.