Salivary IgA Anti-Citrulline Protein Antibodies Associated With Higher Rheumatoid Arthritis Activity

Illustration showing the structure of an antibody, or immunoglobulin, molecule. These Y-shaped molecules have two arms that can bind to specific antigens, for instance viral or bacterial proteins. In doing so, they mark the antigen for destruction.
Researchers characterized the IgA anti-citrulline protein antibodies responses in the saliva and serum in relation to the clinical picture and to risk factors among patients with rheumatoid arthritis.

The presence of salivary immunoglobulin (Ig)A anti-citrulline protein antibodies (ACPAs) may identify patients with rheumatoid arthritis (RA) who have higher disease activity, according to data published in Arthritis Research & Therapy.

This cross-sectional study included analyses for ACPA of IgA isotype in saliva and serum samples from 196 patients with RA and 101 healthy blood donors. Subclasses IgA1 and IgA2 ACPA were also analyzed in the paired samples. All assessments were carried out with modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP).

Patients were queried regarding their smoking habits, and investigators assessed functional ability of patients with the Swedish version of the health assessment questionnaire (HAQ). The researchers also assessed disease activity using the 28-joint disease activity score (DAS28) in relation to the presence or absence of salivary IgA ACPA.

The mean disease duration in the RA group was 12.2 years, and the majority (80%) of patients were women. In total, 12% of the patients with RA had IgA ACPA in the saliva. Additionally, IgA1 was found in 10% and IgA2 was positive in 9%. According to the investigators, IgA ACPA in serum was reported in 45% of patients, while IgA1 was found in 44%, and IgA2 was found in 39%.

There was a moderate correlation between levels of IgA ACPA in the saliva with serum levels of IgA (r=0.455) and IgA1 (r=0.434). Patients with salivary IgA ACPA had a higher mean erythrocyte sedimentation rate (25 vs 19 mm in the first hour; P =.031), DAS28 (3.5 vs 2.7; P =.04), tender joint count (2.0 vs 1.0; P =.039), HAQ (1.0 vs 0.7; P =.006), and patient global assessment score (44 vs 31; P =.03). There were no associations between the antibodies and smoking, shared epitope, or radiographic damage.

A limitation of the study’s radiographic outcome included the lack of formal scoring, as this outcome was based on radiologist-written reports.

The researchers noted that their findings suggest “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