Identification of a novel autoantibody directed against small ubiquitin-like modifier activating enzyme in dermatomyositis

Objective Myositis-specific autoantibodies (MSAs) are directed against cell machinery proteins such as aminoacyl–transfer RNA synthetases, signal recognition particle, Mi-2, and CADM-140. Because serologic subsets can define patients with specific clinical manifestations, the identification of further MSAs may help to identify additional disease subsets within the myositis spectrum. Methods Sera from 20 adult patients with dermatomyositis (DM) were screened for autoantibodies. Two patients were further characterized due to the presence of the same novel immunoprecipitation (IP) pattern on sodium docecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and similar clinical manifestations. Both patients presented with cutaneous disease, followed by proximal myositis 6 months later. Both patients had associated nonspecific interstitial pneumonia but no signs of malignancy. The novel targets were identified using a combination of IP, SDS-PAGE, and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. Results Indirect HEp-2 immunofluorescence on sera from both patients displayed a diffuse, coarse, speckled, nucleolar-sparing pattern. IP revealed the presence of previously uncharacterized bands at ∼40 kd and ∼90 kd in both patients. The novel targets were identified as the small ubiquitin-like modifier 1 (SUMO-1) activating enzyme A subunit and SUMO-1 activating enzyme B subunit. Conclusion These findings reveal previously uncharacterized autoantibodies directed against a protein involved in posttranslational modification, the SUMO activating enzyme, in 2 patients with DM who had similar clinical features, including severe skin disease and interstitial pneumonia.