Hints of Rheumatoid Arthritis in the General Population


Approximately one percent of the general population carries the auto-antibodies associated with rheumatoid arthritis, a new study shows.

Approximately one percent of the general population carries the auto-antibodies associated with rheumatoid arthritis, a new study shows.

While previous studies have shown that as many as 1.7 percent of the general population carries anti-citrullinated protein antibodies (ACPAs), 1 percent is still telling because it indicates a heightened risk of developing rheumatoid arthritis for a population that may not yet be displaying symptoms.

When joint pain is combined with anti-citrullinated protein antibodies, the risk of developing rheumatoid arthritis is greater. In fact, previous studies have shown that when patients with joint pain show subclinical inflammation on MRI, they are more often ACPA-positive than patients without MRI-confirmed inflammation.

The new study, published online Jan. 2 in the Annals of the Rheumatic Diseases, is based on a review of data from a populated-based study from the Netherlands called Lifelines. Records from 40,136 adult men and women were assessed and of these, 401, or 1 percent, had an ACPA level of at least 6.2 U/mL. Among patients who were ACPA-positive, 22.4 percent had rheumatoid arthritis (15.2% met the criteria for RA and 7.2% were self-reported). By contract, among participants without rheumatoid arthritis, 311, or .8 percent, were ACPA-positive.

Led by Elisabeth Brouwer, M.D., of the University Medical Center Groningen in the Netherlands, researchers evaluated the prevalence anti-citrullinated protein antibodies as well as related associations in a predominantly Caucasian cohort.

The ACPA status can provide important information on both diagnosis and prognosis, the Dutch researchers wrote. In this study, ACPA positivity was significantly associated with older age, female gender, smoking, joint complaints, rheumatoid arthritis and first degree relatives with rheumatism. Among patients without rheumatoid arthritis, but were positive for ACPA, their symptoms most often included older age, smoking and joint complaints.

Few studies have evaluated the prevalence of anti-citrullinated protein antibodies in a population-based context, yet recent studies in Japan and Turkey have confirmed anti-citrullinated protein antibodies prevalence in the general population.

Other studies have shown that as many as 55-91 percent of patients with rheumatoid arthritis are ACPA-positive as compared to up to 9 percent of healthy controls. Other studies show that ACPA positivity can occur for up to 10 years before a patient develops arthritis. A prospective study of 374 individuals with joint pain who were positive for either ACPA or IgM-rheumatoid, 35 percent developed arthritis after 12 months.

The presence of anti-citrullinated protein antibodies positivity alone is not enough to predict the development of rheumatoid arthritis and should be evaluated in the context of other clinical characteristics.  For example, the European League Against Rheumatism Standing Committee on Investigative Rheumatology has suggested that more information about anti-citrullinated protein antibodies testing, early symptoms of rheumatoid arthritis and related risk factors are necessary to develop better predictive models for rheumatoid arthritis.

“The strong association of ACPA positivity with RA and joint complaints supports the importance of ACPA screening in persons with joint/musculoskeletal complaints,” Brouwer and colleagues wrote.



This research was supported in part by the Dutch Arthritis Association, and Biobanking and Biomolecular Research Infrastructure.



A van Zanten, S Arends, C Roozendaal, et al. “Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands,” Annals of the Rheumatic Diseases. Published online January 2, 2017. DOI: 10.1136/annrheumdis-2016-209991.


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