Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis.
Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test=anti-CCP/anti-CAP ratio>1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p=0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p=0.071) and C-reactive protein (p=0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Anna
A
Svärd
Alf
A
Kastbom
Yngve
Y
Sommarin
Thomas
T
Skogh
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001667:Binding, Competitive; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D056747:Immunomodulation; D007596:Joints / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012463:Saliva / Q000276:immunology*
D007071:Immunoglobulin A, Secretory; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide