Objectives: We have previously identified autoantibodies to a novel autoantigen small ubiquitin-like modifier activating enzyme (SAE) associated with dermatomyositis (DM). The aim of this study was to establish the frequency of anti-SAE autoantibodies in a UK myositis cohort and investigate clinico-immunogenetic associations.
Methods: Clinical data and sera were studied from 266 patients recruited to the Adult Onset Myositis Immunogenetic Collaboration. Myositis sera, control sera including 250 patients with other connective tissue diseases and 50 healthy subjects were screened using radio-immunoprecipitation. Immunodepletion was performed on all sera immunoprecipitating 40 and 90 kDa bands to confirm the presence of anti-SAE. DNA from 202 myositis patients was genotyped for HLA-DRB1 and DQB1; DQA1 data were inferred.
Results: Eleven out of 266 myositis patients (4%) were positive for anti-SAE which was found exclusively in DM with a frequency of 8%. Anti-SAE patients had a high frequency of cutaneous lesions including heliotrope (82%) and Gottron’s rash (82%). Nine/11 (82%) had systemic features and 7/9 (78%) developed dysphagia. Seven/9 (78%) presented with skin disease before myositis onset. All anti-SAE patients possessed at least one copy of HLA-DQB1*03. HLA-DRB1*04-DQA1*03-DQB1*03 was a significant risk factor in anti-SAE positive vs. anti-SAE negative patients (haplotype frequency 18% vs. 6%, p=0.0001, OR 5.7, 95% CI 1.9-17.3).
Conclusions: Anti-SAE is a myositis specific autoantibody that identifies a subset of patients with adult DM. The majority of anti-SAE patients presented with cutaneous disease and progressed to myositis with systemic features including dysphagia. This novel autoantibody has a strong association with the HLA-DRB1*04-DQA1*03-DQB1*03 haplotype.