Autoantibodies are clinically useful for phenotyping patients across the spectrum of autoimmune rheumatic diseases. Using serum from a patient with Sjögren's syndrome (SS), we detected a new specificity by immunoblotting. This study was undertaken to identify this autoantibody and to evaluate its disease specificity.
A prominent 40-kd band was detected when immunoblotting was performed using SS patient serum and lysate from rat dorsal root ganglia (DRGs). Using 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing, the autoantigen was identified as calponin 3. Anti-calponin 3 antibodies were evaluated in sera from patients with primary SS (n = 209), patients with systemic lupus erythematosus (SLE; n = 138), patients with myositis (n = 138), patients with multiple sclerosis (MS; n = 44), and healthy controls (n = 46) by enzyme-linked immunosorbent assay. Expression of calponin 3 was assessed by immunohistochemistry.
Calponin 3 was identified as a new autoantigen. Anti-calponin 3 antibodies were detected in 23 (11.0%) of the 209 SS patients, 12 (8.7%) of the 138 SLE patients, 7 (5.1%) of the 138 myositis patients, 3 (6.8%) of the 44 MS patients, and 1 (2.2%) of the 46 healthy controls. Among SS patients, the frequency of anti-calponin 3 antibodies was highest in those with neuropathies (7 [17.9%] of 39). In this subset, the frequency of anti-calponin 3 antibodies differed significantly from that in the control group (P = 0.02). Calponin 3 was expressed primarily in rat DRG perineuronal satellite cells but not neurons.
Calponin 3 is a novel autoantigen. Antibodies against this protein are found in SS and associate with the subset of patients experiencing neuropathies. Intriguingly, we found that calponin 3 is expressed in DRG perineuronal satellite cells, suggesting that these may be a target in SS.