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.

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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