Clinical and human leucocyte antigen class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK Caucasian adult-onset myositis
Betteridge, Z. E., Gunawardena, H., Chinoy, H., North, J., Ollier, W. E. R., Cooper, R. G., McHugh, N. J. and Immunogene, U. K. A. O. M., 2009. Clinical and human leucocyte antigen class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK Caucasian adult-onset myositis. Annals of the Rheumatic Diseases, 68 (10), pp. 1621-1625.
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Objectives: Autoantibodies to a novel autoantigen small ubiquitin-like modifier activating enzyme (SAE) associated with dermatomyositis (DM) have previously been identified. The aim of this study was to establish the frequency of anti-SAE autoantibodies in a UK myositis cohort and investigate clinicoimmunogenetic 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 participants 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 patients with myositis was genotyped for human leucocyte antigen (HLA)-DRB1 and DQB1; DQA1 data were inferred. Results: Out of 266 patients with myositis, 11 (4%) were positive for anti-SAE, which was found exclusively in DM with a frequency of 8%. Patients with anti-SAE had a high frequency of cutaneous lesions including heliotrope (82%) and Gottron rash (82%). Of the 11, 9 (82%) had systemic features and 7 of 9 (78%) developed dysphagia. Of those nine, seven (78%) presented with skin disease before myositis onset. All patients with anti-SAE 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 versus patients who were anti-SAE negative (haplotype frequency 18% vs 6%, p < 0.001, OR 5.7, 95% CI 1.9 to 17.3). Conclusions: Anti-SAE is a myositis-specific autoantibody that identifies a subset of patients with adult DM. The majority of patients with anti- SAE 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.
|Creators||Betteridge, Z. E., Gunawardena, H., Chinoy, H., North, J., Ollier, W. E. R., Cooper, R. G., McHugh, N. J. and Immunogene, U. K. A. O. M.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
Faculty of Humanities & Social Sciences > Health
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