Higher Levels of Arthritis Autoantibodies Associated With Clinically Suspect Arthralgia in Patients Without RA

Senior woman with joint pain in her hand
Senior woman with joint pain in her hand
Researchers assessed whether arthritis autoantibodies can predict clinically suspect arthralgia in ACPA-positive patients without rheumatoid arthritis.

Anticitrullinated protein antibodies (ACPA)-positive individuals without rheumatoid arthritis (RA) who develop clinically suspect arthralgia have higher levels of arthritis-associated autoantibodies, according to study results published in Rheumatology.

Several antibodies are associated with the development of RA, including rheumatoid factor (RF) and ACPA. In a follow-up analysis of 308 individuals (62% women) from the population-based Lifelines cohort in the Netherlands who were ACPA-positive but without RA, investigators aimed to evaluate whether the presence of arthritis-associated antibodies, along with immunoglobulin G (IgG) ACPA, was predictive of clinically suspect arthralgia.

Patient serum samples were tested for IgA and IgG ACPA, IgM and IgA RF, and anticarbamylated protein (anti-CarP) antibodies at baseline. Researchers evaluated clinically suspect arthralgia using the Connective Tissue Disease Screening Questionnaire after 2 years of follow-up; a total of 178 patients (57.8%) responded to the questionnaire.

Of the 308 individuals without RA who tested positive for IgG ACPA, 166 (53.6%) also tested positive for IgA ACPA, 130 (42.2%) for IgM RF, 73 (23.7%) for IgA RF, and 42 (13.6%) for anti-CarP. There was a strong correlation (P <.0001) between all the autoantibodies.

Among patients who were assessed for clinically suspect arthralgia, 46.6% scored positive for ≥1 joint complaint. The presence of serum IgM (P =.005), as well as serum IgA and IgM RF levels (P =.03 for both), were higher in the group with joint complaints. A total of 75 study participants, including 62 in the joint complaint group, were found to have clinically suspect arthralgia. Serum levels of IgG (P =.04) and IgA ACPA (P =.02), as well as IgM RF (P =.02), were significantly higher in the group with vs without clinically suspect arthralgia. Compared with individuals without clinically suspect arthralgia, those with clinically suspect arthralgia were seropositive for ≥3 autoantibodies (16 vs 24, respectively; P =.01). In addition, significantly more individuals in the clinically suspect arthralgia group tested positive (n=6 vs 12, respectively) for the combination of IgG ACPA, IgM RF, and anti-CarP antibodies (P =.03).

After adjusting for age, sex, and smoking status, joint complaints and seropositivity for ≥3 antibodies were significantly associated with clinically suspect arthralgia. However, RF IgM positivity and IgG ACPA and IgM levels did not remain significantly different between the 2 groups. In the joint complaint group, anti-P gingivalis levels were correlated with IgM (P =.006) and IgA RF levels (P =.007). In the clinically suspect arthralgia group, anti-P gingivalis levels were strongly correlated with IgA RF levels (P =.0006), as well as IgG ACPA (P =.014), IgA ACPA (P =.05), and IgM RF (P =.001).

“[M]easuring multiple arthritis autoantibodies in combination with clinical characteristics identifying clinically suspect arthralgia may help in the early identification of RA development,” the researchers concluded. “Levels of anti-P gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.”


Westra J, Brouwer E, Raveling-Eelsing E, et al. Arthritis autoantibodies in individuals without rheumatoid arthritis: follow-up data from a Dutch population-based cohort (Lifelines) [published online June 28, 2020]. Rheumatology (Oxford). doi:10.1093/rheumatology/keaa219