Salivary immunoglobulin A (IgA) anticitrullinated protein antibodies (ACPAs) have been detected in a small subset of patients with rheumatoid arthritis (RA), and they are associated with higher levels of disease activity, according to study results published in Arthritis Research & Therapy.

In the current study, researchers sought to characterize salivary and circulating IgA ACPAs relative to disease characteristics and risk factors in patients with RA.

Patients with established RA from the County of Dalana, Sweden, were included in the Secretory ACPA in RA (SARA) study, with enrollment from 2012 to 2013. Participants were randomly selected from among those with planned follow-up visits at the Rheumatology Clinic, Falun Hospital, Sweden. Healthy blood donors were enrolled as control participants. Participants were required to provide at least 0.5 mL of saliva during the 10-minute sampling time to be included in the study. Paired saliva and serum samples were collected from patients during their visit to the rheumatology clinic. All participants were requested to refrain from eating, drinking liquids other than water, brushing their teeth, or smoking 1 hour before saliva sampling.

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Overall, a total of 196 patients with RA and 101 healthy blood donors were enrolled in the SARA study. Using enzyme-linked immunosorbent assays that targeted reactivity to a cyclic citrullinated peptide, paired saliva and serum samples from all participants were evaluated for ACPA of IgA isotype, as well as for subclasses IgA1 and IgA2. Cutoff levels for positive serum and saliva tests were set at the 99th percentile for blood donors.

Results of the study showed that IgA ACPA in saliva was detected in 12% of patients with RA; IgA1 and IgA2 were reported in 10% and 9% of patients with RA, respectively. On the other hand, IgA ACPA in serum was found in 45% of patients with RA, IgA1 in 44% of patients, and IgA2 in 39%. Levels of IgA ACPA in saliva samples correlated significantly with serum levels of IgA (r =.455; P <.001).

Further, at the time of sampling, the presence of salivary IgA ACPA was linked to higher erythrocyte sedimentation rate, 28-joint disease activity, tender joint count, and patient global assessment at the time the samples were obtained. However, none of the antibodies were associated with smoking, HLA/DRB1/shared epitope, or radiographic damage.

One of the study limitations was the fact that the radiographic outcome was based on written reports by radiologists and not formal scoring.

Researchers concluded, “This [study] suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.”


Roos Ljungberg K, Börjesson E, Martinsson K, Wetterö J, Kastbom A, Svärd A. Presence of salivary IgA anti-citrullinated protein antibodies associate with higher disease activity in patients with rheumatoid arthritis. Arthritis Res Ther. 2020;22(1):274. doi:10.1186/s13075-020-02363-0