Abstract
BackgroundCirculating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. Therefore, we aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA).MethodsRA patients (n = 196) and healthy blood donors (n = 101), included in the cross-sectional study “Secretory ACPA in Rheumatoid Arthritis” (SARA), were analyzed for ACPA of IgA isotype, and for subclasses IgA1 and IgA2 ACPA in paired saliva and serum samples using modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP). Cutoff levels for positive tests were set at the 99th percentile for blood donors. Antibody levels were related to clinical characteristics, radiographic damage, smoking habits, and carriage of HLA-DRB1/shared epitope (SE).ResultsIgA ACPA in the saliva was found in 12% of RA patients, IgA1 occurred in 10%, and IgA2 in 9%. In serum, IgA ACPA was found in 45% of the patients, IgA1 in 44%, and IgA2 in 39%. Levels of IgA ACPA in the saliva correlated significantly with serum levels of IgA (r = 0.455). The presence of salivary IgA ACPA was associated with a higher erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joint count, and patient global assessment at the time of sampling. None of the antibodies was associated with smoking, SE, or radiographic damage.ConclusionSalivary IgA ACPAs were detected in a subset of RA patients in association with higher disease activity. This suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.
Highlights
Mucosal surfaces, rather than the joints, are proposed as sites of initial triggering events in rheumatoid arthritis (RA) development, in anti-citrulline protein antibody (ACPA)-positive disease [1, 2]
By including 196 RA patients of which 12% tested positive for IgA anti-citrullinated protein antibodies (ACPA) in the saliva, we achieved 80% power at alpha = 0.05 to detect a difference in Disease activity score 28 (DAS28) of 0.9 units between patients positive vs. negative for IgA ACPA in saliva
Occurrence of IgA ACPA and IgA ACPA subclasses in the saliva and serum The 196 RA patients included in the Secretory ACPA in Rheumatoid Arthritis” (SARA) study had a mean disease duration of 12.2 years and 80% were women
Summary
Rather than the joints, are proposed as sites of initial triggering events in rheumatoid arthritis (RA) development, in anti-citrulline protein antibody (ACPA)-positive disease [1, 2]. IgG ACPA is often analyzed, but ACPA exists in several isotypes including IgA, and the latter has been identified in several mucosal fluids including saliva [5, 6]. Circulating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. We aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA)
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